title: A Multicentre, Open Label, Nonrandomised, Non-interventional, Observational, Safety Study in Subjects Using Insulin Detemir for the Treatment of Insulin Dependent Type 1 or Type 2 Diabetes Mellitus: The PREDICTIVE™ Study: Predictable Results and Experience in Diabetes Through Intensification and Control to Target: an International Variability Evaluation

acronym: PREDICTIVE™

summary:
This study is conducted in Africa, Asia, Europe, Japan and South America. The aim of this observational study is to evaluate the incidence of serious adverse reactions (SARs) while using Levemir® (insulin detemir) under normal clinical practice conditions.

Study conducted globally in 26 countries. Some countries participated in the study for only 3 months (Austria, Brazil, Denmark, Germany, Israel, Lebanon, Slovenia, Russia, and Turkey), while others extended their participation to 6 (Belgium/Luxembourg, Czech Republic, Greece, India, Italy, Netherlands, Saudi Arabia, South Africa, South Korea, Sweden, Tunisia, and United Kingdom/Ireland) and 12 months (Finland, France, and Japan), respectively.

ReferenceCitation: Dornhorst A, Lüddeke HJ, Honka M, Ackermann RW, Meriläinen M, Gallwitz B, Sreenan S; PREDICTIVE Study Group. Safety and efficacy of insulin detemir basal-bolus therapy in type 1 diabetes patients: 14-week data from the European cohort of the PREDICTIVE study. Curr Med Res Opin. 2008 Feb;24(2):369-76.

ReferenceCitation: Honka M. [Results of the PREDICTIVE project in the Czech Republic]. Vnitr Lek. 2008 Apr;54(4):361-7. Czech.

ReferenceCitation: Dornhorst A, Lüddeke HJ, Koenen C, Meriläinen M, King A, Robinson A, Sreenan S; PREDICTIVE Study Group. Transferring to insulin detemir from NPH insulin or insulin glargine in type 2 diabetes patients on basal-only therapy with oral antidiabetic drugs improves glycaemic control and reduces weight gain and risk of hypoglycaemia: 14-week follow-up data from PREDICTIVE. Diabetes Obes Metab. 2008 Jan;10(1):75-81. Epub 2007 Nov 22.

ReferenceCitation: Dornhorst A, Lüddeke HJ, Sreenan S, Koenen C, Hansen JB, Tsur A, Landstedt-Hallin L. Safety and efficacy of insulin detemir in clinical practice: 14-week follow-up data from type 1 and type 2 diabetes patients in the PREDICTIVE European cohort. Int J Clin Pract. 2007 Mar;61(3):523-8.

ReferenceCitation: Dornhorst A, Lüddeke HJ, Sreenan S, Kozlovski P, Hansen JB, Looij BJ, Meneghini L; PREDICTIVE Study Group. Insulin detemir improves glycaemic control without weight gain in insulin-naïve patients with type 2 diabetes: subgroup analysis from the PREDICTIVE study. Int J Clin Pract. 2008 Apr;62(4):659-65. doi: 10.1111/j.1742-1241.2008.01715.x.

ReferenceCitation: Lüddeke HJ, Sreenan S, Aczel S, Maxeiner S, Yenigun M, Kozlovski P, Gydesen H, Dornhorst A; PREDICTIVE Study Group. PREDICTIVE- a global, prospective observational study to evaluate insulin detemir treatment in types 1 and 2 diabetes: baseline characteristics and predictors of hypoglycaemia from the European cohort. Diabetes Obes Metab. 2007 May;9(3):428-34.

ReferenceCitation: Sreenan S, Virkamäki A, Zhang K, Hansen JB; PREDICTIVE study group. Switching from NPH insulin to once-daily insulin detemir in basal-bolus-treated patients with diabetes mellitus: data from the European cohort of the PREDICTIVE study. Int J Clin Pract. 2008 Dec;62(12):1971-80. doi: 10.1111/j.1742-1241.2008.01939.x. Erratum in: Int J Clin Pract. 2009 Jan;63(1):176-7:178-80.

ReferenceCitation: Palmer JL, Goodall G, Nielsen S, Kotchie RW, Valentine WJ, Palmer AJ, Roze S. Cost-effectiveness of insulin aspart versus human soluble insulin in type 2 diabetes in four European countries: subgroup analyses from the PREDICTIVE study. Curr Med Res Opin. 2008 May;24(5):1417-28. doi: 10.1185/030079908X297295 . Epub 2008 Apr 8.

ReferenceCitation: Valentine WJ, Goodall G, Aagren M, Nielsen S, Palmer AJ, Erny-Albrecht K. Evaluating the cost-effectiveness of therapy conversion to insulin detemir in patients with type 2 diabetes in Germany: a modelling study of long-term clinical and cost outcomes. Adv Ther. 2008 Jun;25(6):567-84. doi: 10.1007/s12325-008-0069-z.

ReferenceCitation: Hermansen K, Lund P, Clemmensen K, Breum L, Kleis Moller M, Mette Rosenfalck A, Christiansen E; Danish PREDICTIVE study group. 3-Month Results from Denmark within the Globally Prospective and Observational Study to Evaluate Insulin Detemir Treatment in Type 1 and Type 2 Diabetes: The PREDICTIVE Study. Rev Diabet Stud. 2007 Summer;4(2):89-97. Epub 2007 Aug 10.

ReferenceCitation: Fontaine P, Gin H, Pinget M, Thivolet C, Hanaire H, Robert JJ, Marre M, Venkatanarasimhachar S. Effect of insulin detemir dose frequency on clinical outcomes in patients with diabetes in PREDICTIVE. Adv Ther. 2009 May;26(5):535-51. doi: 10.1007/s12325-009-0033-6. Epub 2009 Jun 2.

ReferenceCitation: Hermansen K, Dornhorst A, Sreenan S. Observational, open-label study of type 1 and type 2 diabetes patients switching from human insulin to insulin analogue basal-bolus regimens: insights from the PREDICTIVE study. Curr Med Res Opin. 2009 Nov;25(11):2601-8. doi: 10.1185/03007990903262885.

ReferenceCitation: Niskanen L, Virkamäki A, Hansen JB, Saukkonen T. Fasting plasma glucose variability as a marker of nocturnal hypoglycemia in diabetes: evidence from the PREDICTIVE study. Diabetes Res Clin Pract. 2009 Nov;86(2):e15-8. doi: 10.1016/j.diabres.2009.08.005. Epub 2009 Sep 10.

ReferenceCitation: Yenigun M, Honka M. Switching patients from insulin glargine-based basal-bolus regimens to a once daily insulin detemir-based basal-bolus regimen: results from a subgroup of the PREDICTIVE study. Int J Clin Pract. 2009 Mar;63(3):425-32. doi: 10.1111/j.1742-1241.2008.01973.x.

ReferenceCitation: Perriello G, Caputo S, De Pergola G, Di Carlo A, Grassi G, Lapolla A, Pata P, Solerte SB, Zaccardi F. Improved glycemic control with weight loss and a low risk of hypoglycemia with insulin detemir: insights from the Italian cohort of the PREDICTIVE study after 6-month observation in type 2 diabetic subjects. Expert Opin Pharmacother. 2011 Nov;12(16):2449-55. doi: 10.1517/14656566.2011.626766. Erratum in: Expert Opin Pharmacother. 2011 Dec;12(17):2765.

ReferenceCitation: Yang L, Christensen T, Sun F, Chang J. Cost-effectiveness of switching patients with type 2 diabetes from insulin glargine to insulin detemir in Chinese setting: a health economic model based on the PREDICTIVE study. Value Health. 2012 Jan-Feb;15(1 Suppl):S56-9. doi: 10.1016/j.jval.2011.11.018.

ReferenceCitation: Sreenan S, Andersen M, Thorsted BL, Wolden ML, Evans M. Increased Risk of Severe Hypoglycemic Events with Increasing Frequency of Non-severe Hypoglycemic Events in Patients with Type 1 and Type 2 Diabetes. Diabetes Ther. 2014 Dec;5(2):447-58. doi: 10.1007/s13300-014-0075-x. Epub 2014 Jul 15.

lead_sponsor: Novo Nordisk A/S

location_country:
Denmark
United Kingdom
Greece
Ireland
Italy
Finland
Czech Republic
Korea, Republic of
France
Israel
Turkey
Belgium
Sweden


type: Other Grant/Funding Number

title: Constitution of a National Cohort of Patients With Metastatic Melanoma Stage IV or Unresectable Stage III With the Objective of Setting up a Epidemiological Monitoring and a Clinico-biological Database, MELBASE

acronym: MelBase

summary:
Prevention of melanoma can be efficient but mortality remains unchanged and 15 to 20% of patients still die from melanoma. Indeed metastatic melanoma is a heterogeneous highly and multiple mutations driven cancer. Significant survival benefit was demonstrated since 2011 with anti-CTLA4, programmed death-1 (anti PD1) antibodies, B-Raf proto-oncogene, serine/threonine kinase (BRAF) and MAP-ERK kinase (MEK) inhibitors. Future improvement of advanced melanoma prognosis will rely on clinico-epidemiological studies and on biological studies aiming to validate and identify new prognostic and predictive factors based upon clinico-epidemiological and histological data, genomic host and tumor alterations, tumor microenvironment characteristics, individual immunological profile and functional imaging. In the context of marketing of costly innovative molecules prospective collection of economic data on treatment and toxicity are required. Large biobanks collecting data from cohorts of advanced melanoma are mandatory for such projects.

MELBASE is a French prospective national cohort enrolling advanced melanoma patients whose objectives are :

To provide an annual instrument panel with a descriptive and correlative analysis of patients with advanced melanoma in France including epidemiological, clinical and biological socio-economic characteristics
to validate and identify new clinical, epidemiological, and biological prognostic factors such as genomic host and tumor alterations, tumor microenvironment characteristics, individual immunological profile in advanced melanoma.
to evaluate the risk-benefit, the impact on treatment on patient quality of life, the management cost of patients treated with the validated and future treatments of metastatic melanoma. The project also aims to define predictive biomarkers of response and toxicity including pharmacogenetics and tumor genetics alterations, tumor microenvironment characteristics, individual immunological profile.

Patients with unresectable stage III or stage IV melanoma will be enrolled prospectively for 1 year with a 5 years follow-up (a total of 2000 patients will be enrolled) from 26 French centers A database of clinical monitoring of metastatic patients will be established and associated with a virtual tumor bank. This national database will be issued from the use of biological, clinical and imaging databases already available in the centers and optimized for this project; this database will also results from the interaction with the French national cancer institute (INCa) genotyping platform.

study_start_date_type: Actual

status: Unknown status

study_completion_date_type: Anticipated

study_type: Observational

time_perspective: Prospective

enrollment_type: Anticipated

ReferenceType: derived

ReferenceCitation: Plaschka M, Benboubker V, Grimont M, Berthet J, Tonon L, Lopez J, Le-Bouar M, Balme B, Tondeur G, de la Fouchardière A, Larue L, Puisieux A, Grinberg-Bleyer Y, Bendriss-Vermare N, Dubois B, Caux C, Dalle S, Caramel J. ZEB1 transcription factor promotes immune escape in melanoma. J Immunother Cancer. 2022 Mar;10(3). pii: e003484. doi: 10.1136/jitc-2021-003484.

ipd_sharing: No

lead_sponsor: Assistance Publique - Hôpitaux de Paris

location_facility: Assistance Publique - Hôpitaux de Paris (AP-HP), Hopital Saint-Louis, centre d'oncodermatologie

location_facility: Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Ambroise Paré

location_facility: Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Bichat

location_facility: Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Cochin

location_facility: Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Avicennes

intervention_type: Other

lead_sponsor_type: academique

status_simplified: Unknown


title: A Comparative, Dose-Escalating, Placebo-Controlled Study of the Efficacy and Safety of PAZ320, Ingested Together With a Standard Meal on Post-Prandial Glucose and Insulin Blood Levels in Type II Diabetic Patients Treated With Metformin

summary: The purpose of this study is to test the efficacy of PAZ320 in diabetic patients.

status: Withdrawn

study_type: Interventional

design_allocation: Randomized

primary_purpose: Treatment

enrollment_type: Actual

lead_sponsor: Boston Therapeutics

location_facility: Department of Internal Medicine, Infectious Diseases and Diabetology Hopital Robert Bisson (Lisieux)

lead_sponsor_type: industriel


title: Evaluation of Lung Clearance Index for Early Detection of Lung Disease in Young Children With Cystic Fibrosis

acronym: LCI

summary:
The purpose of this study is to determine the efficacy of a non invasive method of detecting the pulmonary disease in order to initiate treatment against cystic fibrosis as soon as possible.

Moreover this screening procedure permits to note the improvement following the treatment and to choose the optimal treatment in term of efficacy.

status: Completed

study_completion_date_type: Actual

primary_purpose: Screening

status_simplified: Completed


acronym: AntiTNF-SN

intervention_type: Drug

title: Phase II Clinical Trial Using Humira in Netherton Syndrome

type: EudraCT Number

source: euctr

summary:
The main objective of this studies therapeutic : to determine the effect of Adalimumab (HumiraR) on clinical inflammatory manifestations of patients with Netherton syndrome after 3 months of treatment , with a post treatment period follow-up of 3 months.

Second objectives are To evaluate the safety of Adalimumab in the context of NS To evaluate the improvement of the quality of life at 3 months To evaluate the improvement of pruritus and pain in the patients To study markers of inflammatory and allergy in NS prior and after treatment Benefit of the study An improvement by at least 20% of the cutaneous signs in these patients who suffer from a genetic incurable, chronic, painful and very afflicting disease would be of a great help for these patients. NS is a major source of social exclusion.

Risks They are inherent to the risks of biotherapies, especially for an anti-TNF therapy, they comprise a risk of infection. Cutaneous infections occur mainly during infancy, and we have therefore chosen to treat patients over 4 years of age in this study.

A close clinical surveillance will be set up (initially every week during the first month of treatment, then every month). This will represents a large number of visits but will provide a high level of security.

Benefits/risks ratio In the absence of curative treatment for these patients with a severe genetic skin disease, the benefits/risks ration clearly appears to be in favour of an expected benefit.


title: Influence of Sodium Intake on Left Ventricular-arterial Coupling in Hypertension: Biomechanical Assessment and Modelisation of Left Ventricular Function With Arterial Pressure

summary: The objective of the present study is to asses the effectiveness of the aorta-ventricular coupling according to low and high sodium intake in 28 controled hypertensive patients.

status: Terminated

lead_sponsor: University Hospital, Montpellier

location_facility: Lapeyronie University Hospital of Montpellier

intervention_type: Dietary Supplement


title: Assessment of βeta Blocker Interruption After Uncomplicated mYocardial Infarction on Safety and Symptomatic Cardiac Events Requiring Hospitalization: The AβYSS Study

acronym: AβYSS

summary: ABYSS is a national, multicenter, randomised, open label trial using the PROBE study design, that will evaluate the non-inferiority of the interruption of ΒB therapy after an uncomplicated MI after six months or more of follow-up compared to the continuation of βB evaluated by the primary endpoint or death, MI, Stroke and rehospitalization for others cardiovascular reasons.

status: Active, not recruiting

ipd_sharing_description: There is not a plan to make IPD available

location_facility: Institut de Cardiologie - USIC - Hôpital Pitié-Salpêtrière

status_simplified: Ongoing


primary_purpose: Other

acronym: IVIG

title: Efficacy of IntraVenous ImmunoGlobulins (IVIG) in Toxic Shock Syndromes (Staphylococcal and Streptococcal): a Paediatric Pilot Study.

lead_sponsor: Hospices Civils de Lyon

summary:
Staphylococcus aureus and Streptococcus pyogenes produce many virulence factors. Some of them are responsible for severe infections in humans. Superantigen toxins synthesized by S. aureus or by S. pyogenes, are responsible for toxic shock syndromes (TSS) which lethality can attain 25% in children with validated criteria of septic shock.

Previous studies, performed in vitro and in vivo in animals, have shown that Intravenous immunoglobulins [IVIG] contain antibodies [Ab] against these toxins and, when used at high concentration, IVIG are able to neutralize their toxicity. However, in all these studies, IVIG administration has been preventive and there is no reliable data demonstrating their therapeutic efficacy in vitro or in vivo in humans or in animals, once the disease is present.

The efficacy of IVIG is established in other pathologies for which the role of the superantigens [superAg] is suspected, like Kawasaki disease in children. The mechanism of action, although not perfectly known, involves at the same time a direct effect on superAg (Ag-Ab complex) and indirect effects like the neutralisation of superAg within the network of anti-idiotype Ab or the neutralisation of the T-cells receptors. Staphylococcal and streptococcal toxic shocks imply bacterial exotoxins that are superAg. It seems thus consistent to imagine a same type of treatment with IVIG. However, there is currently no evidence of the efficacy of IVIG in this indication. One of the explanations relies on the lack of statistical power of previous adult studies, which principal objective was to show a reduction of the mortality. Taking into account the low prevalence of TSS, it has been hard to recruit enough patients to have the required statistical power. Moreover, some works have been extracted from larger studies on septic shock and the definitions of the TSS were nor always very reliable. Lastly, if the investigators consider the definition of the TSS as mentioned by the " Centre for Disease Control " [CDC], for which any hypotension, even a simple orthostatic hypotension, serves the diagnosis of TSS as long as the other symptoms are present, it is obvious that many patients are likely to be recruited in a study although it is highly probable that their health will get better with a " standard " treatment. The definition of a " real " TSS can be refined, keeping the CDC criteria, but changing the hypotension criterion in a more accurate criterion as described in the " surviving sepsis campaign ", internationally accepted and based on norms adapted to the age for paediatric forms.

IVIG therapy is very expensive and TSS is not recognized as indication of IVIG according to their marketing authorization. The feasibility of a randomized controlled study with this treatment needs to be assessed as it would be hazardous to conduct a large prospective RCT without having first assessed this feasibility in terms of recruitment rates, consent rates or compliance rates. Inclusion, randomisation and collect of inform consent in the context of severe shock are challenging and require evaluation of feasibility. The sample size calculation of the large study on mortality required estimations of the event in the specific population of children with criteria of septic shock. Surrogates markers of outcome need to be better defined. For example it would be useful to determine the evolution of organ dysfunctions with and without IVIG treatment in this population.

Various organ failure scores, used upon admission and later on, have been validated in adults and in children. The absence of improvement of the Paediatric logistic organ dysfunction (Pelod) score over time is a good indicator of mortality in Paediatric intensive care unit (PICU). It could be used as surrogate marker to evaluate the efficacy of IVIG.


title: Inpatient Evaluation of an Automated Closed-Loop Control-to-Range System

acronym: CTR

summary:
The purpose of this study is to test an insulin management system ("Control-to-Range (CTR) system") in an inpatient setting to see if the system is safe and effective enough to test in a future at-home study. The system includes (1) a DexCom Seven Plus Continuous Glucose Monitoring (CGM) device that measures the blood sugar, (2) a laptop computer that determines how much insulin is needed, and (3) an Insulet OmniPod insulin pump that delivers the insulin.

The study will include two hospital stays consisting of meals and exercise scenarios. Both hospital stays will be for 24+ hours during the day and night. The study will include about 50 individuals at 7 clinical centers in the United States, France, Israel, and Italy.

ReferenceCitation: Chase HP, Doyle FJ 3rd, Zisser H, Renard E, Nimri R, Cobelli C, Buckingham BA, Maahs DM, Anderson S, Magni L, Lum J, Calhoun P, Kollman C, Beck RW; Control to Range Study Group. Multicenter closed-loop/hybrid meal bolus insulin delivery with type 1 diabetes. Diabetes Technol Ther. 2014 Oct;16(10):623-32. doi: 10.1089/dia.2014.0050. Epub 2014 Sep 4.

ReferenceCitation: Zisser H, Renard E, Kovatchev B, Cobelli C, Avogaro A, Nimri R, Magni L, Buckingham BA, Chase HP, Doyle FJ 3rd, Lum J, Calhoun P, Kollman C, Dassau E, Farret A, Place J, Breton M, Anderson SM, Dalla Man C, Del Favero S, Bruttomesso D, Filippi A, Scotton R, Phillip M, Atlas E, Muller I, Miller S, Toffanin C, Raimondo DM, De Nicolao G, Beck RW; Control to Range Study Group. Multicenter closed-loop insulin delivery study points to challenges for keeping blood glucose in a safe range by a control algorithm in adults and adolescents with type 1 diabetes from various sites. Diabetes Technol Ther. 2014 Oct;16(10):613-22. doi: 10.1089/dia.2014.0066. Epub 2014 Jul 8. Erratum in: Diabetes Technol Ther. 2015 Jan;17(1):68. Vistenin, Roberto [corrected to Visentin, Roberto].

lead_sponsor: Jaeb Center for Health Research

location_country:
United States
Italy
Israel
France

location_facility: Schneider Children's Medical Center of Israel

location_facility: University of Colorado Health Sciences Center- Barbara Davis

intervention_type: Device


title: Comprehensive Analysis of Regional Myocardial Function in Response to Dobutamine Stress in Metabolic Syndrome and Type 2 Diabetic Patients. Effect of Cardiac Adiposity, Inflammation and Hyperglycaemia

summary:
Summary.

Theoretical Rationale:

The left ventricular myocardial performance results from a complex interplay between linear deformations (longitudinal, circumferential and radial) and twist/ untwist mechanics. These components of myocardial mechanics can be assessed, at rest and during stress conditions, by high resolution echocardiography using the "2D-strain" technology and constitute good indexes of tissue intrinsic contractility / relaxation properties. Type 2 diabetes (T2DM) and metabolic syndrome (MS) are associated with an increased risk for cardiac diseases. While several clinical studies have reported, particularly in T2DM, a diastolic dysfunction (concept of "diabetic cardiomyopathy"), the existence of impaired regional myocardial function, with altered intrinsic contractility properties, remains largely unanswered, especially in the SM. Stress echocardiography is very interesting to reveal myocardial dysfunction, discrete or absent at rest. To the best of our knowledge, no scientific study is, however, today available on the kinetics of linear strains and twist/untwist dynamics in response to stress in T2DM as well as SM. The epicardial adipose tissue is the source of production of important pro-inflammatory cytokines that have the potential, through an exacerbation of oxidative stress, to impair coronary endothelial function, increase fibrosis, but also directly affect cardiomyocyte calcium homeostasis. An increase in epicardial adipose tissue is consensually reported in T2DM and SM and is clearly associated with coronary atherosclerosis. A link between cardiac adiposity and overall cardiac function, particularly diastolic, is now suggested but to our knowledge no study has challenged its association with myocardial dysfunction in T2DM as SM patients.

Objectives and Methodology: - To investigate regional myocardial linear deformations and torsion, at rest and in response to a dobutamine stress, in asymptomatic T2DM and SM patients without clinical complications, - to study the links between expected regional myocardial abnormalities and inflammation, hyperglycemia and cardiac adiposity. A control group of healthy individuals matched for sex and age will also be included.

All the subjects will benefit from a clinical, anthropometric and biological evaluation. In addition, conventional echocardiography (remodelling and global diastolic and systolic functions) complemented by a functional analysis by tissue Doppler imaging will be performed. Furthermore, 2D cine loops will be recorded in the apical 4, 3 and 2- chamber views for the objective assessment of myocardial longitudinal deformations as well as in the parasternal short axis (base and apex) for the evaluation of the circumferential deformations and basal and apical rotations and left ventricular torsion, at rest and under low dose of dobutamine (110 and 120 bpm).

design_allocation: Non-Randomized

primary_purpose: Diagnostic

lead_sponsor: University of Avignon


title: Integrated Management of Care Pathway in Oncology. Impact on the Delay of Therapeutic Management and the Satisfaction of Patients and Carers

acronym: PASSION

summary:
A centralized unit for integrated management of care pathway in Oncology has been created. This unit settles the patients' appointments (biopsy, intravenous device, chemotherapy, imaging, oncologist...).

The aim of this study is to assess the delay between the first appointment with the oncologist and the beginning of the antitumoral treatment, and therefore evaluate the efficacy of the care pathway unit.

The second aim is to assess the satisfaction of patients and health care teams.

time_perspective: Cross-Sectional

ipd_sharing: Yes

intervention_type: Behavioral


title: Community and Hospital Experiences for Patients Treated by Oral Chemotherapy at the University Hospital of Caen: Analysis of the Process and Its Dysfunctions

acronym: PARCOURS

summary:
PARCOURS is a non-interventional research study evaluating dysfunctions in the continuous city-hospital journey of a patients cohort treated by oral chemotherapy (60 patients followed for 3 months).

References used are the National Cancer Institute recommendations for the oral chemotherapy treated outpatients.

Parameters found are : information exchanged, ambulatory and hospital monitoring in case of adverse event and adherence to treatment. The study includes also a medico-economic evaluation (hospitalization and transport spending in case of dysfunction in the patient's journey). Deviations will be analyzed.

lead_sponsor: University Hospital, Caen


title: Improvement in the Detection of Aggressive Prostate Cancer by Targeted Biopsies Using Multiparametric MRI Findings

summary:
Background: Prostate cancer is difficult to detect using ultrasound. As a result, in case of suspicion of prostate cancer based on digital rectal examination (DRE) or Prostate Specific Antigen (PSA) level, it is currently recommended to perform "blinded" systematically distributed biopsies with 10-18 samples obtained from predefined locations in the gland.

These so-called systematic biopsies (SB) may lead to improper patient management by (i) missing clinically significant cancer, especially in the anterior half of the gland that tends to be undersampled, (ii) inducing chance detection of clinically insignificant cancer foci that may result in overtreatments, (iii) undersampling the tumor foci and thus underestimating their volume and aggressiveness.

Multiparametric Magnetic Resonance Imaging (mp-MRI) has yielded promising results in detecting aggressive (Gleason ≥7) prostate cancers. Several monocenter studies showed that targeted biopsies (TB) based on mp-MRI findings could detect significantly more aggressive cancers, reduce the diagnosis of clinically insignificant cancers, and better evaluate the aggressiveness of detected cancers than SB. However, these monocenter studies only provide low-level evidence and three recent independent reviews of literature concluded that there was a need for a robust multicenter trial evaluating the diagnostic yield of TB as compared to SB. This is particularly important since many academic and private centers in France already perform mp-MRI before prostate biopsy in daily routine. Therefore the risk is that this approach becomes the norm without being properly evaluated and it is crucial and urgent to perform a controlled multicentric study to provide high-level evidence as to whether mp-MRI should or should not be obtained before prostate biopsy.

One controlled multicentric study has been published recently in which SB and TB had been obtained by two different operators in 95 patients. TB yielded a significantly higher detection rate for all prostate cancers (69% vs 59%, p=0.033) and for clinically significant cancers (67% vs 52%, p=0.0011). However, this study was limited by the fact that patients with negative mp-MRI were not included.

Research hypotheses: There is currently no robust multicenter trial comparing prostate TB based on mp-MRI findings versus the current standard of care (SB). We propose a multicentre prospective trial comparing the results of SB and TB performed in the same patients by two independent operators. Our hypothesis is that TB detects aggressive (Gleason ≥7) cancers in a significantly higher percentage of patients than SB.

Main objective: To compare the percentage of patients with "clinically significant cancer" (using definition A, i.e. cancer with Gleason score ≥7) detected by SB versus TB.

ReferenceCitation: Rouvière O, Puech P, Renard-Penna R, Claudon M, Roy C, Mège-Lechevallier F, Decaussin-Petrucci M, Dubreuil-Chambardel M, Magaud L, Remontet L, Ruffion A, Colombel M, Crouzet S, Schott AM, Lemaitre L, Rabilloud M, Grenier N; MRI-FIRST Investigators. Use of prostate systematic and targeted biopsy on the basis of multiparametric MRI in biopsy-naive patients (MRI-FIRST): a prospective, multicentre, paired diagnostic study. Lancet Oncol. 2019 Jan;20(1):100-109. doi: 10.1016/S1470-2045(18)30569-2. Epub 2018 Nov 21.

location_facility: Groupe Hospitalier Pellegrin - CHU de Bordeaux

location_facility: Institut Universitaire du Cancer de Toulouse (IUCT) Oncopole - CHU de Toulouse

location_facility: CLIMAL (Centre Libéral Imagerie Médicale Agglomération Lille)

location_facility: Nouvel Hopital Civil - CHU de Strasbourg

intervention_type: Procedure


title: A French Prospective, Observational Cohort Study of Patients With Fabry Disease Treated With Migalastat - the MIGA-FAB Study

summary: This is a cohort study to evaluate the effects of migalastat, on long-term safety, effectiveness, and quality of life (QOL) in patients with Fabry disease.

lead_sponsor: Amicus Therapeutics France SAS

location_facility: CHU de Grenoble site Nord, Hôpital Albert Michallon


title: Treatment-related Benefit and Satisfaction in Fabry Patients. Insight in Patients Expectations and Preferences (SATIS-Fab)

summary:
In the shared decision-making process, patients should express their expectations and preferences regarding treatment to the physician. A specific questionnaire addressing needs and expectations of Fabry patients has been built at the initiative of Amicus. In addition, this questionnaire also evaluates the benefit of treatment from the patient's perspective. Nothing is known until now on patient's expectations, potential clustering of patients regarding their expectations and evaluation of treatment benefit from the patients perspective.

Study objectives are differentiated according to the study phase (inclusion and follow-up). At inclusion, the primary objective is to cluster patients according to their needs and expectations regarding treatment. During follow-up, the primary objective is to evaluate treatment benefit in relation with patients needs and expectations.

location_facility: Groupe hospitalier Diaconesses Croix Saint-Simon


title: The Ketogenic Diet for Alzheimer's Disease: a Randomized Controlled Feasibility Study.

acronym: CETOMA

summary:
The ketogenic diet (KD) is a metabolic shift, which stimulates the liver oxidation of fatty acids to produce ketone bodies. These ketone bodies represent an alternative fuel source for the brain. The benefits of KD in epilepsia have been demonstrated for decades. This diet may also provide benefits in Alzheimer's disease (AD) where neuronal glucose utilization declines from the early stage. Besides, the KD could decrease neuroinflammation, oxidative stress and enhance mitochondrial biogenesis. In murin models of AD, KD or Medium Chain Triglycerides consumption were associated with lower neuroinflammation but also with a diminution of neuropathologic features of AD (amyloid and tau lesions in the brain). Moreover, behavioural effets and improvements in memory and motor function have been highlighted. In humans, recent studies suggest cognitive benefits (memory, executive function) in AD, including in the Mild Cognitive Impairment (MCI) stage. The feasibility and the adherence to the diet proved to be correct, in small samples, in particular in MCI individuals over a short follow-up period (3 to 6 months).

This study aims at examining the feasibility of a KD followed-up for one year in participants with early AD (N=70). Change in brain metabolism will be assessed using PET scan after 12 months, comparing KD with control diet. The effects on cognition, quality of life and daily living functioning will be analysed. The safety, nutritional changes and adhesion to the diet will be monitored throughout the study.

study_start_date_type: Anticipated

status: Not yet recruiting

location_facility: Cognitive Neurology Center - Lariboisière Fernand Widal University Hospital (APHP)


title: Donepezil Use Versus Non-drug Approach in Treatment of Newly Diagnosed Alzheimer's Disease : a Multicentric, Randomized, Open Study : the CHOLINE-2 Study

summary:
Donepezil, as well as the other symptomatic drugs of Alzheimer's disease, is not any more reimbursed by the French healthcare system, due to a controversy about its efficiency. French health authorities currently preconize a non-rug approach based on cognitive remediation or stimulation.

The aim of this study is to compare the efficiency of the 2 approaches (non-drug versus donepezil) on the symptoms of Alzheimer's disease after 6 months of treatment.

status: Recruiting


type: Other Identifier

title: Nonverbal Communication in Aged People With and Without Neurodegenerative Disease: Study of Sensorimotor Synchronization to Music

acronym: MAMUS

summary: Musical interventions improve the emotional state of patients with Alzheimer's disease (AD) while having a positive impact on the caregiver's well-being. However, the factors that could be responsible for this positive effect remain unknown. Among these, the sensory-motor synchronization (SMS) of movements to the musical rhythm, frequently observed during musical activities and possible up to the advanced stages of AD, could modulate the emotional state. Several recent studies have shown that rhythmic training (or SMS) influences the organism at the motor, cognitive and social levels while activating the cerebral reward circuit. This action that generates pleasure also facilitates non-verbal emotional expression. However, the conditions that modulate SMS and their relationship to nonverbal communication, emotional, behavioral and cognitive state have not yet been studied in healthy or pathological elderly.

lead_sponsor: University Hospital, Lille


title: Treatment of Primary Plasma Cell Leukaemia in Subjects Under the Age of 70: Phase II Multicentre Study

acronym: LPP

summary:
Plasma cell leukaemia is a rare variety of multiple myeloma with a poor prognosis. Plasma cell leukaemia is defined as: at least 2,000 circulating plasma cells per µL for a blood leukocyte count higher than 10,000/µL or 20% of plasma cells for a leukocyte count less than 10,000/µL. Plasma cell leukaemia can be either primary, when it constitutes the first manifestation of the disease, or secondary in the setting of relapsed/refractory multiple myeloma. Primary plasma cell leukaemia (PPL) is a rare disease, representing only 1 to 2% of all cases of multiple myelomas at diagnosis. As the annual incidence of multiple myeloma in France is about 4,000 new cases, an estimated 40 to 80 new cases of PPL would be observed each year.

Few data are currently available in the literature concerning the pathophysiology and therapeutic management of PPL, and are derived from retrospective series based small numbers of patients. The prognosis of PPL in response to conventional chemotherapy remains poor with a median survival of 7 to 14 months. However, longer survivals have been obtained with intensive therapy and haematopoietic stem cell transplantation (allogeneic or autologous HSCT).

The investigators propose to perform a prospective study of the management of patients with PPL under the age of 70 years, in combination with a laboratory study: 12 weeks of induction chemotherapy by liposomal Bortezomib-Dexamethasone-Doxorubicin (PAD) alternating with Bortezomib-Dexamethasone-Cyclophosphamide (VCD) for a total of 4 cycles. Peripheral blood stem cell collection after mobilization by G-CSF will be performed after high-dose Cyclophosphamide chemotherapy. Autologous HSCT conditioned by high-dose Melphalan will be performed during the following month for all responding patients. During the 3 months after this first autologous HSCT, allogeneic HSCT with attenuated conditioning will be proposed in patients under the age of 66 years in complete remission with a suitable donor, and another systematic autologous HSCT will be proposed in all other patients. For all patients not treated by allogeneic HSCT, consolidation/maintenance therapy will be performed 3 months after the second autologous HSCT: 4 quarterly consolidations with Bortezomib-Lenalidomide-Dexamethasone (VRD) with maintenance by 2 months of Lenalidomide between these cycles, for a total duration of one year.

The laboratory assessment will consist of blood and bone marrow samples systematically obtained at diagnosis for plasma cell phenotyping by cytometry, cytogenetics, FISH, study of the gene expression profile and SNParray. A DNA bank and plasma bank will be constituted. The investigators also propose to study residual disease by cytometry (after the first autologous HSCT, before and at the end of the consolidation/maintenance phase), as it increasingly appears to have a major impact on survival in multiple myeloma.

lead_sponsor: Centre Hospitalier Universitaire, Amiens

location_facility:
CHU Besançon
CHU Nantes
CHU Tours
CH Pays d'Aix
CH Dunkerque
CHU Strasbourg
CHU Caen
CHU Clermont Ferrand
CHU Poitiers
CHU Rennes
CHU Toulouse
CHU Nancy
CHRU Lille
CHU Nice
Hospices Civils de Lyon
CHU Amiens
AP-HP
CHU Dijon


title: A Phase IIa Exploratory Study Evaluating the Anti-psoriatic Effect of Daivobet® Gel Applied Then Removed After 10 Minutes, Daivobet® Gel Applied Then Removed After 20 Minutes, Daivobet® Gel Applied for 24 Hours and Daivobet® Gel Vehicle Applied for 24 Hours

summary: The purpose of this study is to evaluate the anti-psoriatic effect of Daivobet® gel applied then removed after 10 minutes (+/- 2 minutes), Daivobet® gel applied then removed after 20 minutes (+/- 2 minutes) compared with Daivobet® gel and Daivobet® gel vehicle applied for 24 hours (+/- 2 hours), using the psoriasis plaque test modified from the method developed by KJ Dumas and JR Scholtz.

lead_sponsor: LEO Pharma

location_facility: Centre de Pharmacologie Clinique Appliquée à la Dermatologie (CPCAD)


title: A Plaque Test Study With LEO 35299 in Psoriasis Vulgaris

summary: The purpose of the study is to evaluate the anti-psoriatic effect of LEO 35299 in different formulations, compared to Daivonex® ointment and Daivonex® ointment vehicle, using the psoriasis plaque test modified from the method developed by KJ Dumas and JR Scholtz.

location_facility: Centre de Pharmacologie Clinique Appliquée à la Dermatologie (CPCAD) - Hôpital l'Archet 2, 151 route Saint-Antoine de Ginestière


title: A Multicenter Open Label Phase II Study of Pomalidomide and Cyclophosphamide and Dexamethasone in Relapse/Refractory Multiple Myeloma Patients Who Were First Treated Within the IFM/DFCI 2009 Trial

acronym: PCD

summary:
Imnovid in combination with dexamethasone is indicated in the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least two prior treatment regimens, including both lenalidomide (Revlimid) and bortezomib (Velcade), and have demonstrated disease progression on the last therapy.

Patients with relapsed and refractory multiple myeloma who have received bortezomib, lenalidomide, dexamethasone combination, considered to be the multiple myeloma optimal treatment, can access to pomalidomide under marketing authorization only as from third line of treatment.

In France this combination is not authorized for marketing for a first line treatment and only patient randomized in the IFM/DFCI 2009 trial received it.

This study concerns patients previously randomized in the IFM/DFCI 2009 trial who have received bortezomib, lenalidomide and Dexamethasone combination in first line, which at progression/relapse time therapeutic opportunities remained limited and who cannot access pomalidomide under marketing authorization.

This study is a multicentre, phase 2, open label, study testing the triple combination of pomalidomide and cyclophosphamide and dexamethasone (PCD) in multiple myeloma patients who are refractory or in first progression/relapse after a first line treatment with bortezomib and lenalidomide, an IMiDs (an Immuno Modulatory Drug and a proteasome inhibitor) according to the IFM/DFCI 2009 trial.

In the IFM/DFCI trial, patients in arm A received eight cycles of the Velcade-Revlimid-Dexamethasone combination followed by 1 year of lenalidomide maintenance, patients in arm B received 3 cycles of Velcade-Revlimid-Dexamethasone combination plus melphalan 200mg/m2 with an autologous transplantation followed by 2 cycles of Velcade-Revlimid-Dexamethasone combination consolidation and 1 year of lenalidomide maintenance.

This study will contain 3 treatment phases:

Study treatment phase:

All patients will receive 4 cycles (28 days) of pomalidomide-cyclophosphamide-dexamethasone combination.

Consolidation phase (depends on the initial randomization in the IFM/DFCI 2009 trial):

For patients previously randomized in IFM/DFCI 2009's arm A:

Melphalan 200 mg/m2 followed by Autologous Transplantation
Three months after, 2 cycles of pomalidomide-cyclophosphamide-dexamethasone combination

For patients previously randomized in IFM/DFCI 2009's arm B:

5 cycles of pomalidomide-cyclophosphamide-dexamethasone combination
Maintenance phase (identical to all patients) subsequent cycles of pomalidomide and Dexamethasone until progression / relapse or discontinuation for any other reason.

For arm B patients, in case relapse occurs at least 12 months after the end of the maintenance IFM/DFCI 2009 trial, they could proceed to a second autologous transplantation and therefore follow the arm A procedure. The decision to proceed to a second transplant will be made by the physician and the patient.

In order to have the same amount of patients enrolled in this trial in the initial Arm A and Arm B of the IFM/DFCI 2009 trial, once 50 patients have been included in either arm A or B, subsequent patients will be eligible if they have not been initially treated as the first 50 patients from either arm.

The primary endpoint is the response rate (Partial Response (PR) or better) after 4 cycles of the triple combination pomalidomide and cyclophosphamide and dexamethasone (PCD) in the studied population using International Myeloma Working Group (IMWG) response criteria.

ReferenceCitation: Garderet L, Kuhnowski F, Berge B, Roussel M, Escoffre-Barbe M, Lafon I, Facon T, Leleu X, Karlin L, Perrot A, Moreau P, Marit G, Stoppa AM, Royer B, Chaleteix C, Tiab M, Araujo C, Lenain P, Macro M, Voog E, Benboubker L, Allangba O, Jourdan E, Orsini-Piocelle F, Brechignac S, Eveillard JR, Belhadj K, Wetterwald M, Pegourie B, Jaccard A, Eisenmann JC, Glaisner S, Mohty M, Hulin C, Loiseau HA, Mathiot C, Attal M. Pomalidomide, cyclophosphamide, and dexamethasone for relapsed multiple myeloma. Blood. 2018 Dec 13;132(24):2555-2563. doi: 10.1182/blood-2018-07-863829. Epub 2018 Oct 3.

lead_sponsor: Institut Curie

location_facility: Institut Universitaire du Cancer Toulouse-Oncopôle (IUCT-O)

location_facility: Centre Hospitalier départemental de Vendée

location_facility: Institut d'Hématologie de Basse Normandie - IHBN


title: Study Comparing the Role of the Laparoscopy Surgical Staging in the Peritoneal Carcinomatosis to Laparotomic Approach

acronym: COELIOCHIP

summary: The peritoneum is the second most common site of recurrence in patients with colorectal cancer. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy improve the prognosis of these patients and incorporates surgical removal of all visible disease followed by chemical destruction of microscopic disease through chemoperfusion. The most validated predictors of outcome are preoperative tumor burden measured in terms of the peritoneal carcinomatosis index (PCI) and completeness of cytoreduction (CC score). Diagnostic laparoscopy prior to resection is widely used in hepatopancreaticobiliary and colorectal cancer and has been shown to be effective in excluding unnecessary laparotomy associated with higher morbidity.

location_facility: Hospices Civils de Lyon - Centre Hospitalier Lyon Sud Service de Chirurgie Générale et Digestive - 165 chemin du grand Revoyet


title: Clinical and Biological Digestive Peritoneal Carcinomatosis Data Base From the French National Network of Peritoneal Surface Malignancies

acronym: BIG-RENAPE

summary:
To access to good quality biological samples is a prerequisite for high level translational research. The BIG-RENAPE study has been established by the French hyperthermic intraperitoneal chemotherapy centers involved in the management of peritoneal surface malignancies.

The main BIG-RENAPE study aim is to create a large multicentric and prospective repository for biological and tissue samples, which will provide a source of materials for a wide array of health related research studies - BIG-RENAPE Biobank-based research: i) validating known and promising biomarkers; ii) identifying new predictive and prognostic factors; iii) evaluating the impact of current health care strategies; iv) standardizing diagnostic and therapeutic management through guidelines; v) developing new drugs.

The BIG-RENAPE Biobank is certified according to NFS 96-900 as a service of processing, storage and transfer of high quality biological (plasma, serum, buffy coat) and tissue (formalin-fixed-paraffin-embedded) samples. Biospecimens are collected at each stage of diagnostic and therapeutic care. The patient and his derivates are anonymized and registered in a national web database reporting disease status, treatments, surgical procedures, pathological diagnosis, quality of life's assessment and long term follow-up. All participants have given their informed consent before any sample. The BIG-RENAPE study was approved by the local Ethical Committee, based on the assessed compliance to French regulatory rules.

primary_purpose: Health Services Research

ReferenceCitation: Bonnefoy I, Mohamed F, Bonnot PE, Benzerdjeb N, Isaac S, Cotte E, Glehen O, Passot G. Risk of Omental Metastases in Patients Undergoing Cytoreductive Surgery for Colorectal Peritoneal Metastases. Dis Colon Rectum. 2020 Sep;63(9):1251-1256. doi: 10.1097/DCR.0000000000001670.

ReferenceCitation: Péron J, Mercier F, Tuech JJ, Younan R, Sideris L, Gelli M, Dumont F, Le Roy B, Sgarbura O, Lo Dico R, Bibeau F, Glehen O, Passot G; on behalf BIG-RENAPE working groups. The location of the primary colon cancer has no impact on outcomes in patients undergoing cytoreductive surgery for peritoneal metastasis. Surgery. 2019 Feb;165(2):476-484. doi: 10.1016/j.surg.2018.07.027. Epub 2018 Sep 7.


title: Assessment of the Safety and Performance of a Lumbar Belt

summary:
Decathlon has developed the Lumbar belt Soft 300 and Mid 500 products which are medical devices designed to reduce pain and improve function during sport practice for athletes with a common subacute or chronic low back pain.

The objective of this multicentre study is to collect data on the related clinical complications and clinical outcomes of market-approved Decathlon Lumbar belt range of products to demonstrate safety and performance of these devices in a real-world setting.

Outcome data collected from this study will provide the basis for Post-Market Surveillance (PMS) reporting, Clinical Study Report (CSR), Clinical Evaluation Report (CER) on Decathlon lumbar belt Soft 300/ Mid 500 devices and support peer-reviewed publications on products performance and safety.

lead_sponsor: Decathlon SE

location_facility: Centre de rééducation et de balnéothérapie Kinés Faches


title: Assessment of the Safety and Performance of a Compression Knee Support in the Prevention of Injuries During Sports Practice

summary: Decathlon has developed kneeSOFT100 product which is medical device designed to reduce pain and joint instability during sport practice. The objective of this multicentre study is to collect data on the related clinical complications and clinical outcomes of market-approved Decathlon kneeSOFT100 product to demonstrate safety and performance of this device in a real-world setting.

location_facility: Centre Hospitalier Universitaire de Lille


title: Assessment of the Safety and Performance of Knee Ligament Supports in the Context of a Return to Sport After Sprain

summary:
Decathlon has developed kneeMID500-STRONG700 products which are two medical devices designed to be used for sport resumption after mild (kneeMID500) or moderate (KneeSTRONG100) knee sprain or after an Anterior Cruciate Ligament surgery.

The difference between these devices is based on the strength of compression and the knee maintain.

The objective of this multicentre study is to collect data on the related clinical complications and clinical outcomes of market-approved Decathlon kneeMID500-STRONG700 products to demonstrate safety and performance of these devices in a real-world setting.


title: Silent Brain Infarction After Endovascular Arch Procedures: Preliminary Results From the STEP Registry

summary: This is the largest study to evaluate incidence and distribution of silent cerebral infarction (SBI) following endovascular repair for disease of the aortic arch. Also, it is the first cohort to include total endovascular arch repair and devices flushed with carbon dioxide (CO2) to prevent gaseous cerebral embolization.

time_perspective: Other

ReferenceCitation: Charbonneau P, Kölbel T, Rohlffs F, Eilenberg W, Planche O, Bechstein M, Ristl R, Greenhalgh R, Haulon S; STEP collaborators. Silent Brain Infarction After Endovascular Arch Procedures: Preliminary Results from the STEP Registry. Eur J Vasc Endovasc Surg. 2021 Feb;61(2):239-245. doi: 10.1016/j.ejvs.2020.11.021. Epub 2020 Dec 22.

lead_sponsor: Medical University of Vienna

location_country: Germany France

location_facility: University Hospital Hamburg-Eppendorf (Hamburg, Germany)

location_facility: Marie Lannelongue Hospital (Paris, France)


title: Efficiency of Ursodesoxycholic Acid in the Treatment of Duodenal Adenomas in Familial Adenomatous Polyposis Patients. URSOPAF

summary: Malignant transformation of adenomas of the duodenum is now the leading cause of death in familial adenomatous polyposis (FAP) patients who had a restorative proctocolectomy. Ursodeoxycholic acid (UDCA) modifies the biliary acid profile and could reduce the severity of duodenal adenomas and prevent such transformation.

ReferenceType: background

ReferenceCitation: Spigelman AD, Williams CB, Talbot IC, Domizio P, Phillips RK. Upper gastrointestinal cancer in patients with familial adenomatous polyposis. Lancet. 1989 Sep 30;2(8666):783-5.

ReferenceCitation: Nugent KP, Farmer KC, Spigelman AD, Williams CB, Phillips RK. Randomized controlled trial of the effect of sulindac on duodenal and rectal polyposis and cell proliferation in patients with familial adenomatous polyposis. Br J Surg. 1993 Dec;80(12):1618-9.

ReferenceCitation: Järvinen HJ, Nyberg M, Peltokallio P. Biliary involvement in familial adenomatosis coli. Dis Colon Rectum. 1983 Aug;26(8):525-8.

ReferenceCitation: Spigelman AD, Owen RW, Hill MJ, Phillips RK. Biliary bile acid profiles in familial adenomatous polyposis. Br J Surg. 1991 Mar;78(3):321-5.

ReferenceCitation: Mower HF, Ray RM, Shoff R, Stemmermann GN, Nomura A, Glober GA, Kamiyama S, Shimada A, Yamakawa H. Fecal bile acids in two Japanese populations with different colon cancer risks. Cancer Res. 1979 Feb;39(2 Pt 1):328-31.

ReferenceCitation: Hill MJ, Drasar BS, Williams RE, Meade TW, Cox AG, Simpson JE, Morson BC. Faecal bile-acids and clostridia in patients with cancer of the large bowel. Lancet. 1975 Mar 8;1(7906):535-9.

ReferenceCitation: Tanida N, Hikasa Y, Shimoyama T, Setchell KD. Comparison of faecal bile acid profiles between patients with adenomatous polyps of the large bowel and healthy subjects in Japan. Gut. 1984 Aug;25(8):824-32.

ReferenceCitation: van der Werf SD, Nagengast FM, van Berge Henegouwen GP, Huijbregts AW, van Tongeren JH. Colonic absorption of secondary bile-acids in patients with adenomatous polyps and in matched controls. Lancet. 1982 Apr 3;1(8275):759-62.

ReferenceCitation: Wilpart M, Mainguet P, Maskens A, Roberfroid M. Structure-activity relationship amongst biliary acids showing comutagenic activity towards 1,2-dimethylhydrazine. Carcinogenesis. 1983 Oct;4(10):1239-41.

ReferenceCitation: Earnest DL, Holubec H, Wali RK, Jolley CS, Bissonette M, Bhattacharyya AK, Roy H, Khare S, Brasitus TA. Chemoprevention of azoxymethane-induced colonic carcinogenesis by supplemental dietary ursodeoxycholic acid. Cancer Res. 1994 Oct 1;54(19):5071-4.

ReferenceCitation: Serfaty L, De Leusse A, Rosmorduc O, Desaint B, Flejou JF, Chazouilleres O, Poupon RE, Poupon R. Ursodeoxycholic acid therapy and the risk of colorectal adenoma in patients with primary biliary cirrhosis: an observational study. Hepatology. 2003 Jul;38(1):203-9.

ReferenceCitation: Parc Y, Piquard A, Dozois RR, Parc R, Tiret E. Long-term outcome of familial adenomatous polyposis patients after restorative coloproctectomy. Ann Surg. 2004 Mar;239(3):378-82.

ReferenceCitation: Parc Y, Desaint B, Fléjou JF, Lefèvre JH, Serfaty L, Vienne A, Kotti S, Simon T, Tiret E. The effect of ursodesoxycholic acid on duodenal adenomas in familial adenomatous polyposis: a prospective randomized placebo-control trial. Colorectal Dis. 2012 Jul;14(7):854-60. doi: 10.1111/j.1463-1318.2011.02816.x.


title: Experience of Relatives and Caregivers of Death in ICU After the Withdrawal of Life-sustaining Therapies, Associated With an Organ Procurement Procedure (Controlled Donation After Circulatory Death).

summary:
Controlled donation after circulatory death (cDCD) refers to organ donation (OD) from patients whose death is defined using circulatory criteria and from whom circulatory death occurs after a planned withdrawal of life-sustaining therapies (WLST) in intensive care units (ICUs). During cDCD, the patient is still alive while OD process is being discussed and organized. Caregivers can be particularly uncomfortable in this scenario. In the specific context of cDCD, developing knowledge on the perceptions and experiences of relatives and ICU caregivers regarding OD is crucial but remains poorly investigated.

Investigators propose to conduct a prospective multicentric observational research to better understand relatives' and ICU caregivers' experience of cDCD. Better understanding their perceptions and experiences will enable to develop interventions to support and guide them throughout this practice.

location_facility: APHP - Lariboisière hospital - réanimation chirurgicale


title: Anatomical Clinical Correlations. Neuropsychological and Brain Medical Imaging Study in Brain Damage Subjects 2 (CORAC2)

summary:
Two groups of subjects will be constitute: (i) patients with circumscribed brain injury (including stroke, vascular malformations, tumor or circumscribed infectious lesions) or degenerative/developmental disorders and selective cognitive disorders; (ii) healthy control subjects.

The objective of this project is to evaluate specific neuropsychological deficits and apply current brain imaging techniques (anatomical, diffusion, functional, magnetic stimulation) to patients suffering from these cognitive deficits due to brain damage, in order to elucidate the brain mechanisms underlying these deficits.


title: Are Bone, Nutritional and Cardiovascular Status of French Children and Adolescents, Correlated With Their Vitamin D Status?

acronym: VITADOS

summary:
Vitamin D is not seen anymore only as a phosphocalcic hormone, but also as having an effect on global health (anti-infective, anti-inflammatory, anti-tumour roles and cardiovascular protection).

The link between vitamin D deficiency and osteomalacia lesions is well-known. In paediatrics, systematic vitamin D supplementation of infants and toddlers, associated with milk enrichment, has allowed an almost total disappearance of rickets. Vitamin D repletion was defined as the minimal concentration that enables the prevention of rickets in children and osteomalacia in adults, that is approximately 8 ng/mL (20 nmol/L). However, in 2010, most of the international experts agreed to set minimal threshold of 25 OH vitamin D serum concentration, higher than the one previously admitted, with a limit of 20 ng/mL (50 nmol/L) to define a vitamin D deficiency and a limit of 30 ng/mL (75 nmol/L) to define vitamin D insufficiency in adults. In the paediatric population, the consensus is less obvious and we consider that a serum concentration of minimum 20 ng/mL is necessary.

A study on more than 200 children from Lyon, followed in the paediatric nephrology unit and having a renal function normal or sub-normal, demonstrated an important prevalence of vitamin D deficiency (75%) in adolescents and pre-adolescents.

Concurrently, the appearance of new bone imaging techniques (especially high-resolution peripheral quantitative computed tomography HR-pQCT) improved bone status evaluation in a non-invasive manner.

Given the new pathophysiological data on pleiotropic role of vitamin D (bone, cardiovascular system, adipose tissue) and given the proportion of French children possibly suffering from vitamin D deficiency, it seems urgent to actualize current recommendations regarding systematic supplementation in vitamin D. This transversal study on 200 healthy children and adolescents will allow to have an overview of vitamin D status in French healthy children and adolescents, studying with non-invasive, safe, reliable and innovative tools, the theoretical targets of vitamin D (bones, cardiovascular system and nutritional status); and then to lay the foundations of therapeutic trials aiming to evaluate the mode of vitamin D supplementation for healthy children and adolescents; while having a cohort for HR-pQCT measurements, that will allow us to have French reference range in a 10-17 year-old population, for this innovative, non-invasive and low radiation exposure technique.


title: Construction of a Composite Clinical-echo Score Predictive of a Risk of Short-term Aggravation of Respiratory Impairment in Patients Suspected of Covid-19

acronym: VIRUS

summary:
With the influx of patients suspected of Covid-19 and the limited number of hospital beds, there is a need for sensitive triage to detect patients at risk of pulmonary complications and therefore requiring hospitalization, but also specific triage to safely discharge patients without risk factors or signs of clinical or ultrasound severity. The use of pulmonary ultrasound in addition to clinical assessment seems appropriate. Indeed, it allows early detection of signs of pneumopathy which, in the current context, most often correspond to Covid-19. These signs include B-lines, which indicate interstitial pulmonary oedema, and an anfractuous and thickened pleural line, or even centimetric parenchymal condensations with a low level of pleural effusion. Conversely, the presence of a medium to large pleural effusion is not very suggestive of the diagnosis of Covid-19. In addition, a lung ultrasound score has been developed and validated to assess the severity of acute respiratory distress and predict the occurrence of acute respiratory distress syndrome. It is based on the performance of a 12-point (6 per hemi-thorax) pulmonary ultrasound with the collection of the presence of B-lines, condensation or pleural effusion. In the hands of a trained operator, this examination takes only a few minutes.

The aim of the study is to develop a score based on clinical and ultrasound evidence to allow early and safer referral than that based on clinical evidence alone. To do this, the study will retrospectively collect clinical and lung ultrasound data from departments that use this technique on a daily basis.

time_perspective: Retrospective

lead_sponsor: Nantes University Hospital


title: Use of Selincro and Impact on Usual Practice

acronym: USE-PACT

summary: USE-PACT is a cohort study of patients initiating Selincro® with one-year follow-up, performed using a random sample of prescribers. The aim of the study is to evaluate the use of Selincro in real-life and its impact on alcohol consumption at one year.

lead_sponsor: University of Bordeaux


title: Echocardiography and PEA Measurements in CRT Therapy

summary: This study used an external endocardial acceleration sensor (sonR sensor), placed on the patient's chest, to time the closure of aortic and mitral valves, and compared its performance with echocardiography.

lead_sponsor: LivaNova

location_facility:
Nouvelles Cliniques Nantaises
CHU Rennes
CHU Pontchaillou
Clinique Bizet


title: Efficacy, Safety and Cost of Comprehensive Versus Standard Remote Monitoring of Patients With Cardiac Resynchronization Therapy

acronym: ECOST-CRT

summary: The primary objective is to determine whether comprehensive remote follow-up in HF patients with CRT will reduce the combined endpoint of all-cause mortality or worsening heart failure hospitalizations, whichever comes first, when compared to basic remote monitoring, over a 27-month follow-up.

primary_purpose: Prevention


title: Study of Intra-monocytic Imiglucerase Kinetic and Its Correlation With Clinical and Biological Gaucher Disease

acronym: CIMI

summary:
Rational: Imiglucerase has been used to treat Gaucher disease since 1997 but data about its pharmacokinetics have been partial; investigators know that imiglucerase undergoes a quick clearance from plasma compartment following the infusion (1/2 life: 1-6 min, from tissue: <24h), an observation apparently contradictory with usual infusion rhythm (one infusion every two weeks). Furthermore, by going by GD response, the rhythm of Infusion is sometimes diminished (for example, every 3 or 4 wks) without pharmacological rational ; In parallel, investigators demonstrated that monocytes represent a satisfactory surrogate of GD target cells and that enzyme activity into monocytes varies between individuals.

Our hypothesis is that enzyme activity into monocyte compartment could be different and could be related to GD response.

Primary purpose: to evaluate the pharmacokinetics of Imiglucerase activity into target cellular compartment depending on dose and frequency of infusions.

Secondary purposes : 1) to establish a possible relationship between the intra-monocytic activity of glucocerebrosidase and the clinical and biological activity of Gaucher disease and to define a possible threshold value of enzyme activity; 2) to establish a better correlation with known biomarkers of disease (routine markers and markers recently identified), which would better predict and / or monitor response to treatment ; 3) to compare the residual and natural rate of activity enzyme intra-monocytic for untreated patients (low severity disease).

lead_sponsor: University Hospital, Clermont-Ferrand


title: Development of a New Non-radioactive Test for Measuring Glomerular Filtration Rate Using the Tetrapeptide N-acetyl-Ser-Asp-Lys-Pro-amide (AcSDKP-NH2)

summary: The purpose of the study is to validate a new reference marker for evaluation of renal function (glomerular filtration rate).

ReferenceType: result

ReferenceCitation: Mesmin C, Cholet S, Blanchard A, Chambon Y, Azizi M, Ezan E. Mass spectrometric quantification of AcSDKP-NH2 in human plasma and urine and comparison with an immunoassay. Rapid Commun Mass Spectrom. 2012 Jan 30;26(2):163-72. doi: 10.1002/rcm.5326.

lead_sponsor: Assistance Publique - Hôpitaux de Paris

location_facility: Clinical Investigation Center, European George Pompidou Hospital


title: Evaluation of the Impact of Personalized Pharmaceutical Collaborative Care Integrated to a Multidisciplinary Psychosocial Program on the Burden Felt by Caregivers of Elderly Patients With Alzheimer's Disease and Related Disorders and Evaluated at 18-month Follow-up

acronym: PHARMAID

summary:
Caring for patients with Alzheimer Disease or Related Disorders (ADRD) is accompanied with a caregiver burden that increases with the progression of the disease. This burden can have physical, psychological, emotional, social and financial issue on the informal caregivers who are often represented as hidden secondary patients. They frequently have a higher risk of developing mood disorders as depression, anxiety, stress, sleep disorders and a lower quality of life associated with a greater use of psychotropic drugs. They also incur higher risk of heart disease and mortality. The embrittlement of the caregiver is a major factor of early institutionalization of patient. In the PIXEL study, the mean age of the men caregivers was 73.9 years and 64.8 for the women caregivers. Elderly themselves, especially spouses, the informal caregivers are also exposed to common chronic diseases and associated polypharmacy with a higher risk of developing drug-related problems due to aging and negligence of their own health care. These risks are increased mainly in the elderly because of changes in pharmacokinetic and pharmacodynamic parameters related to aging, acute or chronic diseases and the potentially inappropriate prescription (PIP). Previous studies have shown the effectiveness and positive impact of optimization of the therapeutics by a clinical pharmacist on the reduction of drug-related problems, length of hospital stay, readmission rates, quality of life and mortality. The patient's medication management is usually delegated to the informal caregiver, who must also manage his own treatment. The caregiver may face difficulties with therapeutics (e.g., inappropriate dosage form, adverse effects and patient refusal) that could impact on its compliance with treatment or that of his relative. No previous study has evaluated the impact of pharmaceutical collaborative care including personalized interview with a clinical pharmacist and optimization of drug prescribing among patients with ADRD and their caregivers.

However, many studies have assessed the effectiveness of non-pharmacological interventions on caregiver burden, mood disorders and the patient institutionalization. Meta-analysis showed a moderate improvement of the caregiver burden.

The main objective of the PHARMAID study is to measure the impact of personalized pharmaceutical collaborative care integrated to a multidisciplinary psychosocial program on the burden of ADRD caregivers and assessed at 18-month follow-up.

ReferenceCitation: Novais T, Moutet C, Delphin-Combe F, Dauphinot V, Colin C, Krolak-Salmon P, Mouchoux C; PHARMAID study group. PHARMAID study protocol: Randomized controlled trial to assess the impact of integrated pharmaceutical care at a psychosocial intervention on caregiver's burden in Alzheimer's disease or related diseases. Contemp Clin Trials. 2017 Feb;53:137-142. doi: 10.1016/j.cct.2016.12.020. Epub 2016 Dec 19.

location_facility: Pharmacy unit and Clinical Research Center VCF (" Aging Brain Frailty ") University hospital of Lyon, Charpennes Hospital / University Lyon / INSERM, U1028; CNRS, UMR5292; Lyon Neuroscience Research Center


title: Comparison of the Analgesic Effect of a New Paracetamol Formulation (Paracetamol UNIFLASH) for Buccal Use and Two Different Doses of an Oral Paracetamol Form Controlled Versus Placebo in Patients Suffering From Moderate Pain Due to a Tooth Extraction.

summary: This study aims to evaluate the analgesic efficacy of single dose of a new paracetamol formulation (paracetamol UNIFLASH) for buccal use in comparison to two different doses of an oral paracetamol form controlled versus placebo.

ipd_sharing_description: At this stage, IPD sharing plan has to been discussed and finalised

lead_sponsor: Unither Pharmaceuticals, France

location_country: Poland France Spain Italy

location_facility: Hospital Odontológico Universitat Barcelona

location_facility: Oral surgery Medical University of Lublin

location_facility: NZOZ Akademicka Poliklinika Stomatologiczna

location_facility: Oral Surgery Department, Central Clinical Hospital

location_facility: Hospitalario Universitario de Santiago (CHUS)

location_facility: Department of maxilla facial Surgery -University of Udine

location_facility: Centro Médico Teknon - Grupo Quironsalud

location_facility: Faculty of Medicine of the UNIVERSITY OF MURCIA

location_facility: Facultad de Odontología de la Universidad de Granada


title: Phase II Randomized Double Blind Clinical Trial of'Imatinib Mesylate STI571 (Glivec®) Versus Placebo in Patients With Severe Cutaneous Scleroderma or Systemic Sclerosis With Severe Cutaneous Involvement.

acronym: SCLEROGLIVEC

summary: In vitro studies have shown that imatinib 1mM inhibits strongly the growth of cutaneous fibroblasts. The hypothesis is that imatinib inhibits PDGFR which is known to be a potential target for the molecule, as recently also proposed after the discovery of autoantibodies activating the PDGF receptors. Recent data indicate that TGFb is also a potential target of imatinib. Cutaneous scleroderma is characterized by progressive cutaneous fibrosis caused by hyperactive dermal fibroblasts. Since no established treatment for skin sclerosis in scleroderma is currently available. This study will test the safety and efficacy of imatinib in the treatment of patients with scleroderma and severe cutaneous involvement.

lead_sponsor: University Hospital, Bordeaux

location_facility: Service de Médecin interne - Hôpital central

location_facility: Service de Dermatologie - service de médecine interne et vasculaire - hopital haut Lévêque - av.de magellan

location_facility: Néphrologie et Médecine interne - CH de Valenciennes

location_facility: Service de Rhumatologie - CHU de Strasbourg

location_facility: Service de dermatologie - CHU de Limoges

location_facility: Service de Médecine interne - CHU de Tours

location_facility: Service de Dermatologie - CHU de Toulouse - Hopital Purpan

location_facility: Service de Dermatologie et services de médecine interne et vasculaire - Hôpital St André - CHU de Bordeaux

location_facility: Service de Rhumatologie, Hôpital Pellegrin-Tondu CHU de Bordeaux

location_facility: Service de Médecine interne - Hôpital Saint Louis


title: Genetic Decryption of Leber Congenital Amaurosis (LCA) in a Large Cohort of Independent Families: Establishment of Genotype-phenotype Correlations and Updating the Clinical Definition of This Retinal Dystrophy

acronym: GENPHENACL

summary:
The main objectives of this study are:

Improve genetic counseling by establishment of prevalences of each of genetic subtypes within a expanded population of patients with LCA taking into account ethnicity of families.
Confirm, refine or modify the genotype-phenotype correlations.

Edit important recommendations for:

The clinical and paraclinical exploration of a new patient based on genotype, especially for extraocular explorations, to book at certain genetic subtypes
Prenatal care of a couple.
Directing families to a therapeutic protocol in progress or in development.
Individualize a panel of families without a mutation in the known genes and identify new genes responsible.


title: Evaluation of Diaphragmatic Function in Mechanically Ventilated Patients With Transient Shear Wave Elastography

acronym: Elasto-ICU

summary:
Mechanical ventilation is a life-saving treatment that can be associated with diaphragm dysfunction, a potentially deleterious acquired disability. It may be the consequence of disuse - under mechanical ventilation, respiratory muscles are unloaded - or the consequence of muscle overuse because of insufficient unloading. Evaluating diaphragm function is therefore crucial to optimally tailor the ventilator assistance. Measurement of transdiaphragmatic pressure (Pdi) is the reference method to assess diaphragm function but it invasiveness hinders the generalization of its use. Previous studies have reported that ultrasound can quantify diaphragm thickening and that diaphragm thickening fraction (TFdi) is a good marker of diaphragm function. Since diaphragm becomes stiffer when it contracts, the investigators aim at exploring whether the measurement of diaphragm stiffness by transient shear wave elastography would improve the evaluation of diaphragm function with ultrasound.

Therefore, the objectives of the study are to evaluate the performance of transient shear wave elastography applied to the diaphragm to estimate Pdi in mechanically ventilated patients as compared to TFdi and to correlate the changes in elastography derived indices, in TFdi and in Pdi into different ventilatory conditions and during a spontaneous breathing trial. Pdi will be obtained using catheters positioned in patients' stomachs and esophagus and diaphragm stiffness will be assessed by measuring the shear modulus of the diaphragm with a dedicated ultrasound machine (Aixplorer, Ultrasonic). TFdi will be also measured as previously reported. Pdi, TFdi and shear modulus will be measured at the end of each four following 10 minutes-conditions: 1) baseline with initial ventilator settings (set by the physician in charge of patient); 2) 25%-increase in pressure support and initial PEEP; 3) 25%-decrease in pressure support and initial PEEP and 4) initial level of pressure support and ZEEP. Finally, the same measurements will be done at the beginning of a 30 minutes spontaneous breathing trial.

ReferenceCitation: Fossé Q, Poulard T, Niérat MC, Virolle S, Morawiec E, Hogrel JY, Similowski T, Demoule A, Gennisson JL, Bachasson D, Dres M. Ultrasound shear wave elastography for assessing diaphragm function in mechanically ventilated patients: a breath-by-breath analysis. Crit Care. 2020 Nov 27;24(1):669. doi: 10.1186/s13054-020-03338-y.


title: A Phase I - II Study to Assess Safety and Efficacy of the Combination of Ponatinib With High or Intermediate-Dose Cytarabine as Consolidation Therapy for Patients With Intermediate-Risk Cytogenetic FLT3-ITD AML iIn First Complete Remission

acronym: PONATINIB-AML

summary:
This project is part of a joint ALFA and GOELAM strategy aiming to improve the survival of patients with newly diagnosed Acute Myeloid Leukemia (AML) aged 18-70 years. The basis of this strategy is to evaluate intensified conventional chemotherapy and targeted drugs in selected disease-risk subgroups of adult patients with non promyelocytic AML. Participation will be proposed to almost all adult patients in France aged 18-70 years and diagnosed with AML.

FLT3 genetic alterations include FLT3 somatic point mutations within the second tyrosine kinase domain and internal duplications of the juxta-membrane domain. This alteration is refered to as FLT3-ITD. The FLT3-ITD mutation is found in around 30% of patients with cytogenetically normal AML. Patients with the FLT3-ITD genotype have been reported to have a poor outcome when treated with conventional chemotherapy with an estimated 4-year relapse-free survival of 25% (Schlenk et al. N Engl J Med 2008). More recently, the prognostic relevance of FLT3-ITD has been studied in the context of integrated genetic profiling. This confirmed the genetic complexity of AML and also that FLT3-ITD was associated with reduced overall survival in intermediate-risk AML. A multivariate analysis of several genetic alterations revealed that FLT3-ITD was the primary predictor of patient outcome. FLT3-ITD mutations were classified in 3 categories: 1) FLT3-ITD with +8, TET2, DNMT3A or MLL-PTD mutations (3-year OS 14.5%); 2) FLT3-ITD with wild type CEBPA, TET2, DNMT3 and MLL-PTD (3-year OS 35.2%) and 3) FLT3-ITD with CEBPA mutations (3-year OS 42%) (Patel JP et al. N Engl J Med 2012). However, FLT3-ITD was not a predictor of response to induction therapy, allowing the introduction of targeted therapies after the induction course.

Several FLT3 inhibitors have been evaluated or are currently being tested in the setting of relapsing AML. In most trials to date, patients were only eligible if the FLT3-ITD mutation was present. Disappointing results were reported with the first generation of FLT3 inhibitors, including lestaurtinib (CEP-701), midostaurin (PKC-412) and sorafenib. Second generation FLT3 inhibitors such as quizartinib (AC220) are currently under investigation with promising results. However, the hematologic toxicity of AC220 will likely present a major limitation in evaluating AC220 combined with standard or high-dose chemotherapy.

Ponatinib (AP24534) is a third generation tyrosine kinase inhibitor targeting the BCR-ABL tyrosine kinase domain. Ponatinib was rationally designed with an extensive network of optimized molecular contacts and triple bonds to accommodate the T315I mutation, a major cause of resistance to tyrosine kinase inhibitors in chronic and advanced phase chronic myelogenous leukemia (CML). Ponatinib also inhibits SRC (IC50: 5.4 nM) and members of the VEGFR, FGFR, and PDGFR families of receptor tyrosine kinases (O'Hare T, Cancer Cell 2009). Despite low activity against FLT3 based on the IC50 value (FLT3 IC50: 12.6 nM compared to BCR IC50: 0.37 nM), ponatinib has recently been reported to have significant cellular activity against the MV4-11 cell line which harbors an FLT3-ITD activating mutation. Ponatinib-induced apoptosis was maximal at 10 nM in vitro and a single dose of 5 and 10 mg/kg had a strong inhibitory effect in vivo in mice bearing MV4-11 xenografts. Primary blast cells from 4 FLT3-ITD AML patients were also tested and ponatinib reduced their viability (IC50: 4 nM) whereas no activity was shown on FLT3-ITD-negative blast cells (Gozgit JM et al. Mol Cancer Ther 2011).

Preliminary data from the phase I clinical trial showed that 15 mg ponatinib was associated with a Cmax of 51.1 nM. Cmax was increased to 111 nM and 149 nM in the 30 mg and 45 mg cohorts respectively. The trough concentrations were 55.3 nM and 61.9 nM for the 30 mg and 45 mg doses respectively (Ariad clinical investigator's brochure, version 3). Results from the ongoing phase II trial in CML patients suggest that the hematological toxicity profile of ponatinib is comparable with that of nilotinib or dasatinib, both of which have been successfully combined with conventional chemotherapy.

Investigators thus aim to combine ponatinib with cytarabine in FLT3-ITD AML patients in first complete remission.

lead_sponsor: Versailles Hospital

location_facility:
Dr Abdelaziz CHAIB
Hôpital Edouard Herriot
Centre Hospitalier de Valenciennes
Dr Christian RECHER
Institut de Cancérologie de la Loire
Centre Hospitalier de Meaux
Centre hospitalier de Versailles
Dr Jacques DELAUNAY
Chu Amiens
Dr Mario OJEDA-URIBE
Dr Edouard RANDIAMALALA
Dr Thorsten BRAUN
CHU Boulogne Sur Mer
Hôpital Claude Huriez
Dr Laurence SANHES
Hôpital La Pitié Salpêtrière
Centre Hospitalier René Dubos
Hôpital Saint Antoine
Dr Stéphanie HAÏAT
Hôpital VICTOR DUPOUY
CHU Nice, Hôpital Archet 1
Marc BERNARD
Hôpital Saint Louis
Centre Hospitalier René Huguenin
Dr Regis COSTELLO
CHU de Besançon
Hôpital Necker Enfants Malades
CHRU Dupuytren
Dr Arnaud PIGNEUX
Dr Emilie LEMASLE
CHU d'Angers
CHU de Dijon
Dr Réda GARIDI
Hôpital d'Instruction des Armées PERCY
CHU de Nîmes
Chr Clemenceau
Hôpital Henri Mondor


title: Granulomatous-Lymphocytic Interstitial Lung Disease (GLILD) Diagnosed in Children and Young Adults With Common Variable Immunodeficiency

acronym: pGLILD

summary: 8 to 22% of patients with common variable immunodeficiency (CVID) will develop Granulomatous Lymphocytic Interstitial Lung Disease (GLILD), which has emerged as a major cause of mortality. Little is known about GLILD in children and young adults. The aim of this study was to describe the clinical, functional, radiological and pathological features of children and young adults diagnosed with GLILD.

ReferenceCitation: Bates CA, Ellison MC, Lynch DA, Cool CD, Brown KK, Routes JM. Granulomatous-lymphocytic lung disease shortens survival in common variable immunodeficiency. J Allergy Clin Immunol. 2004 Aug;114(2):415-21.

ReferenceCitation: Park JH, Levinson AI. Granulomatous-lymphocytic interstitial lung disease (GLILD) in common variable immunodeficiency (CVID). Clin Immunol. 2010 Feb;134(2):97-103. doi: 10.1016/j.clim.2009.10.002. Epub 2009 Nov 8. Review.

lead_sponsor: Central Hospital, Nancy, France

location_facility:
Chu Besancon
Chru Dijon Bourgogne
Hôpital Necker Enfants Malades
CHRU Nancy
CHU Montpellier
CHRU Bordeaux


title: Anti-tumor Specific Immune Response in Head and Neck Cancers

acronym: CORISAT

summary:
The purpose is the description of anti-tumor immune responses in general and according to clinical stage and disease free survival (DFS: survival without recurrence (local or distant)) in patients with Head & Neck Squamous Cell Carcinoma

Secondary purposes are:

Study of relationship between anti-tumor immune response and qualitative (yes/no) and quantitative (number) presence of circulating tumor cells (CTCs);
Study of relationship between qualitative (yes/no) and quantitative (number) presence of CTCs and clinical stage as well as DFS
Study of relationship between anti-tumor immune response and clinical stage as well as DFS.

location_facility: Service ORL - Institut Louis Mathieu - CHRU NANCY


title: Aging,Sleep and Cognitive Process

acronym: SOMVIE

summary: The aim of the study is to determine the impact of aging, circadian rhythms and sleep deprivation on executive performances. Volunteers will complete a 40-hour extended wakefulness period in constant condition (semi-recumbent posture in bed, constant dim light levels < 10 lux, food and liquid intake at regular intervals) in order to control the circadian system. The volunteers will not be allowed to sleep in the sleep deprivation protocol ("high sleep pressure protocol") and will adopt a short wakefulness/sleep cycle (150/75 minutes) in the multiple nap protocol ("low sleep pressure protocol"). Tests and scales will be repeated every 3H45

primary_purpose: Basic Science

location_facility:
Genpphass
Uh Purpan
Medes-Imps


acronym:
DURIGAST

 DURIGAST

title: A Randomized Phase II Study Evaluating FOLFIRI + Durvalumab vs FOLFIRI + Durvalumab and Tremelimumab in Second-line Treatment of Patients With Advanced Gastric or Gastro-oesophageal Junction Adenocarcinoma

lead_sponsor: Federation Francophone de Cancerologie Digestive

location_facility:
Privé - Clinique Maurice Tubiana
Privé - Clinique Saint Côme
Ch - Centre Hospitalier de Cholet
Privé - Infirmerie Protestante
Privé - Clinique Des Cèdres
Privé - Clinique Capio Belharra
Privé - Polyclinique Bordeaux Nord
Chu - Hôpital La Miletrie
Privé - Hôpital Privé Paul D'Egine
Chu - Hôpital Estaing
Chu - Hôpital Morvan
Ch - Centre Hospitalier de Carcassonne
Ch - Centre Hospitalier de Bézier
Chu - Hôpital Côte de Nacre
Privé - Clinique Sainte Catherine
Chu - Hôpital Jean Minjoz
Ch - Hôpital Côte Basque
Prive - Institut Montsouris
Privé - Hôpital Privé D'Antony
Chu - Hôpital Robert Debré
Ch - Hopitaux Civils de Colmar
Ch - Hôpital Victor Dupouy
Chu - Hôpital Sud
Ch - Hôpital Duchenne
Chu - Hôpital Hôtel Dieu
Ch - Centre Hospitalier
Ch - Hôpital Germon Et Gauthier
Ch - Hôpital Claude Bernard
Ch - Hôpital Henri Duffaut
Privé - Pôle Santé Léonard de Vinci
Ch - Chp Du Cotentin
Prive - Clinique Jean Mermoz
Privé - Clinique de L'Europe
Chu - Aphp - Hôpital Saint Louis
Privé - Clinique Tivoli

summary:
Gastric adenocarcinoma is the 4th most frequent cancer and the 2nd leading cause of cancer mortality. Most of the patients have metastatic, locally advanced or recurrent unresectable disease. So, systemic treatment remains an important issue especially since chemotherapy improves survival and quality of life (compared to best supportive care alone).

Second-line chemotherapy-based treatment improves overall survival (OS) as compared to best supportive care alone in patients with an acceptable general condition (performance status 0-2). Indeed, with docetaxel monotherapy there was a significant difference in overall survival for the chemotherapy arm with a median of 5.2 versus 3.6 months in best supportive care alone arm (HR=0.67, p=0.01). Irinotecan monotherapy also significantly improves overall survival compared to supportive care alone in a phase III study (4.0 versus 2.4 months; HR=0.48, 95%CI 0.25-0.92; p=0.012).

Based on a phase III trial FOLFIRI (5-FU plus irinotecan) is one most used regimen in second-line in European countries, especially in France. FFCD 0307 trial, a phase III comparing FOLFIRI-ECX (epirubicin-cisplatin-capecitabine) to the reverse sequence (ECX-FOLFIRI), showed that both sequences are possible.

Preliminary results in metastatic gastric cancer with anti-PD1 mAbs are highly promising. In a trial with pembrolizumab, only PD-L1 positive tumors were eligible to the treatment with a cut off at 1%. Thirty-nine patients were enrolled and 67% had received at least two prior chemotherapy regimens. The overall response rate was 22%. The median PFS and OS were 1.9 months and 11.4 months, respectively. KEYNOTE-059 Phase 2 multicohort study with pembrolizumab monotherapy in advanced gastric cancer treatment has been presented at ASCO 2017 meeting. Among 259 patients included in the trial response rate was 11.6%. OS was 5.6 months. Response rates were 15.5% in PDL1+ tumors versus 6.4% in PDL1- tumors and 57.1% in MSI tumors versus 9% in MSS tumors. Up until now, overlap between microsatellite instability and PD-L1 expression is unknown in gastric cancer. An anti-PD-L1 mAb (avelumab) was evaluated in a phase Ib expansion study (n=20, Japanese patients), with 15% of objective response rate and 11.9 weeks for progression-free survival. A second cohort with avelumab included 55 patients for maintenance therapy after first-line chemotherapy, with 7.3% of objective response rate and 14 weeks of PFS. Phase I/II CheckMate-032 evaluated nivolumab (anti-PD-1) ± ipilimumab (anti-CTLA4) at different doses in advanced gastric cancer (17). The overall response rate was between 8% to 24% and the median OS between 4.8 to 6.9 months according to treatment arm.

Others anti-PD1/anti-PD-L1/anti-CTLA4 mAbs are also currently under investigation in gastric cancer alone or in combination with chemotherapy. Nevertheless, up until now there is no published data concerning ICI plus chemotherapy in gastric cancer. The present randomized multicentric non-comparative phase II study aimed to assess the rate of patients alive and without progression at 4 months with advanced gastric or gastro-oesophageal junction (GEJ) adenocarcinoma, pre-treated with fluoropyrimidine + platinum +/- taxane, with two arms Folfiri plus durvalumab versus Folfiri plus durvalumab plus tremelimumab. Indeed, most patients in the French multicentric first-line GASTFOX trial (506 patients planned between 2017 and 2020) can be included in the second-line setting in the DURIGAST trial. Due to the lack of data concerning Folfiri plus durvalumab plus tremelimumab combination, a safety run-in phase will be performed at the beginning of the DURIGAST trial.


title: A Comparative, Randomized, Double-blind, 3-arm Parallel, Phase III Study to Evaluate the Efficacy and Safety of a Fixed Dose Combination of Nefopam/Paracetamol Taken Orally in Moderate to Severe Pain After Impacted Third Molar Extraction

summary: This study aims to evaluate the analgesic efficacy of single and multiple doses of a new fixed dose combination of nefopam hydrochloride 30 mg and paracetamol 500mg taken orally in comparison to each single component.

location_country:
United Kingdom
Russian Federation
Hungary
France
Belgium

location_facility: BARTS HEALTH NHS TRUST Royal London Hospital

location_facility: LLC Center for interdisciplinary dentistry & neuro

location_facility: State Medico-stomato Univ., by A.I. Evdokimov

location_facility: Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi Oktatókórház,

intervention_type: Combination Product


title: Treatment of Anemia With Epoetin Beta in Low Risk Myelodysplastic Syndrome With Analysis of the Impact on Quality of Life and Functional Capacity of Patients

acronym: EPO-QoL

summary:
Chronic anemia is the symptom most frequently found at diagnosis in low risk myelodysplastic syndrome. It generates an increased rate of morbidity and mortality in this population of patients whose median age is high and the rate of co-mobidities important. The historical treatment is limited to transfusion support with a significant impact on quality of life and the incidence of secondary haemosiderosis, which contributes to the emergence of co-morbidities, especially cardiovascular. Treatment with rHuEPO allows for overall erythroid response in 40-60% of patients treated.

In this trial, the investigators intend to study the interest of a treatment with epoetin beta in patients with anemia <10 g / dL in the context of a myelodysplastic syndrome with IPSS score <1.

In addition to studying the erythroid response, the investigators will measure the impact on quality of life and functional performance.

Patients will receive epoetin beta (60 000UI/week). Response will be assessed after 12 and 24 weeks of treatment.

lead_sponsor: Groupe Francophone des Myelodysplasies

location_facility: Centre Hospitalier de la région d'Annecy

location_facility: Centre Hospitalier Universitaire de STRASBOURG


acronym: TIME

title: Randomized Phase II Study of First-line FOLFIRI Plus Cetuximab for 8 Cycles Followed by Either Single-agent Cetuximab as Maintenance Therapy or Observation in Patients With Wild-type KRAS and NRAS Metastatic Colorectal Cancer

lead_sponsor: UNICANCER

location_facility: Centre Hospitalier Intercommunal de Toulon

location_facility: Centre Hospitalier Universitaire d'Angers

location_facility: Centre hospitalier Départemental de Vendée - Les Oudairies

location_facility: Centre de Cancérologie du Grand Montpellier - Clinique Clementville

location_facility: Centre Hospitalier Intercommunal Cote Basque

summary: National multicentric phase II trial evaluating whether single agent cetuximab is effective as maintenance therapy after 8 cycles of first line FOLFIRI plus cetuximab in mCRC patients with KRAS and NRAS wild-type genes, assessed by progression-free survival at 6 months after start of maintenance therapy.


title: A Phase II Study of Decitabine in Patients With Chronic Myelomonocytic Leukemia

summary: The aim of this study is to determine the therapeutic efficacy of Decitabine in patients with chronic myelomonocytic leukemia (CMML) diagnosis according to WHO criteria either untreated or previously treated with Hydrea or Etoposide (given orally), non intensive chemotherapy or intensive chemotherapy given more than 3 months before inclusion.

ReferenceCitation: Itzykson R, Kosmider O, Renneville A, Gelsi-Boyer V, Meggendorfer M, Morabito M, Berthon C, Adès L, Fenaux P, Beyne-Rauzy O, Vey N, Braun T, Haferlach T, Dreyfus F, Cross NC, Preudhomme C, Bernard OA, Fontenay M, Vainchenker W, Schnittger S, Birnbaum D, Droin N, Solary E. Prognostic score including gene mutations in chronic myelomonocytic leukemia. J Clin Oncol. 2013 Jul 1;31(19):2428-36. doi: 10.1200/JCO.2012.47.3314. Epub 2013 May 20.

ReferenceCitation: Braun T, Itzykson R, Renneville A, de Renzis B, Dreyfus F, Laribi K, Bouabdallah K, Vey N, Toma A, Recher C, Royer B, Joly B, Vekhoff A, Lafon I, Sanhes L, Meurice G, Oréar C, Preudhomme C, Gardin C, Ades L, Fontenay M, Fenaux P, Droin N, Solary E; Groupe Francophone des Myélodysplasies. Molecular predictors of response to decitabine in advanced chronic myelomonocytic leukemia: a phase 2 trial. Blood. 2011 Oct 6;118(14):3824-31. doi: 10.1182/blood-2011-05-352039. Epub 2011 Aug 9.

location_facility:
Hôpital Boulogne Sur Mer
CHU de Bicêtre
Centre Hospitalier Joffre
Hôpital Versailles
Hôpital Avicenne
CHU de
Hopital Hotel Dieu
Hopital d'Instruction des Armées Percy
Hematology Dpt, Hopital Purpan
CHR La Source orléans
Hoiptal St Louis
Hôpital Saint-Antoine.
CHU Bretoneau
Hôpital Avignon
Centre Hospitalier du Mans
Centre Hospitalier Sud-Francilien
CHU de Reims
CHU de nantes
CHU Haut-Lévèque
Institut gustave Roussy
CH Angers
CHU d'Amiens
Hopital Henri Mondor
Hôpital Archet1
Hopital Cochin
Institut Paoli Calmettes
CHU de Dijon
Hopital de la Cote Basque
Hopital Necker
Centre Henri Becquerel
CHU Caremeau


title: CAlcified Lesion Intervention Planning Steered by OCT.

acronym: CALIPSO

summary:
Calcified lesions are very frequent among coronary artery disease stenotic lesions.

The prevalence of calcifications ranges from 30 to 40% (by angiography evaluation) but is higher when analyzed by intra coronary imaging.

Calcified lesions are very frequent among coronary artery disease stenotic lesions. The prevalence of calcifications ranges from 30 to 40% (by angiography evaluation) but is higher when analyzed by intra coronary imaging.

The presence of calcifications increases the risk of adverse evolution after PCI , including stent restenosis, thrombosis and need for repeat revascularisation. Specific and appropriate tools can be used for calcified lesions management , including high pressure non compliant balloons, intravascular lithotripsy and rotablator. Intra vascular OCT has a high sensitivity and specificity for calcium detection among coronary artery lesions. Compared to IVUS, OCT allows a better quantification of calcium sheets (depth extension ) . Several intra coronary imaging based calcified lesions management algorithms have been proposed , but none have been validated in clinical practice.

lead_sponsor: Institut Mutualiste Montsouris

location_facility:
Clinique Saint Augustin
L'Hôpital Privé du Confluent
Hôpital Louis Pasteur
Ch de Bastia
Polyclinique les Fleurs
Clinique Saint-Hilaire
CHU de Poitiers
CHU de Clermont-Ferrand
CHU Nîmes
Institut Arnaud Tzanck,
CHU de Bordeaux
Clinique Pasteur
Institut Mutualiste montsouris
CHU de Besançon


title: NEoadjuvant Dose-dense MVAC In cOmbination With Durvalumab (MEDI4736) and Tremelimumab in Muscle-invasive Urothelial Carcinoma

acronym: NEMIO

summary: This is an open label, phase I/II clinical trial to evaluate the efficacy and safety of 2 cycles of durvalumab without (Arm A) or with (Arm B) tremelimumab in association with ddMVAC as neoadjuvant therapy in patients with MIUC.

ReferenceCitation: Thibault C, Elaidi R, Vano YA, Rouabah M, Braychenko E, Helali I, Audenet F, Oudard S. Open-label phase II to evaluate the efficacy of NEoadjuvant dose-dense MVAC In cOmbination with durvalumab and tremelimumab in muscle-invasive urothelial carcinoma: NEMIO. Bull Cancer. 2020 Jun;107(5S):eS8-eS15. doi: 10.1016/S0007-4551(20)30281-2.

ipd_sharing_description: No plan to share

lead_sponsor: Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie

location_facility:
Hôpital Saint André, CHU de Bordeaux
Institut Claudius Regaud
Sasu Roc37
Institut Paoli Calmettes
Centre Antoine Lacassagne
Hia Begin
Hôpitaux universitaires de Strasbourg
Centre Eugene Marquis
Hôpital Européen Georges Pompidou
Groupe Hospitalier Pitié-Salpetrière
Hôpital Cochin
Institut Gustave Roussy
CHU Henri-Mondor
Centre Leon Berard
Institut Mutualiste Montsouris


title: Triple Site Ventricular Stimulation for CRT Candidates

acronym: TRIV

summary:
Despite technological progresses the rate of non-responders to cardiac resynchronization therapy (CRT) remains close to 30%. This inconsistent effect of CRT might be due to incomplete resynchronization as dyssynchrony can persist in 25% to 30% of patients during CRT.

One might hypothesize that stimulating the ventricles at a single site is suboptimal and that stimulating multiple left ventricular (LV) or right ventricular (RV) sites may improve ventricular resynchronization and, consequently, its hemodynamic and clinical effects. First studies have suggested that 1 RV + 2 LV pacing sites configurations increased significantly dP/dt, pulse pressure, LV end-diastolic pressure, and is associated with more LV remodeling and better responder rate compared with pacing a single LV site. First studies with 2 RV+LV pacing sites configuration demonstrated increased dP/dt and cardiac output and a decrease of the cardiac dyssynchrony.

The present pilot trial was designed to examine the 6-month safety of biventricular stimulation with 2 right ventricular (RV) and 1 left ventricular (LV) leads - main objective- and to assess its clinical benefit.

ReferenceCitation: Anselme F, Bordachar P, Pasquié JL, Klug D, Leclercq C, Milhem A, Alonso C, Deharo JC, Gras D, Probst V, Piot O, Savouré A. Safety, feasibility, and outcome results of cardiac resynchronization with triple-site ventricular stimulation compared to conventional cardiac resynchronization. Heart Rhythm. 2016 Jan;13(1):183-9. doi: 10.1016/j.hrthm.2015.08.036. Epub 2015 Sep 26.

lead_sponsor: Medtronic Cardiac Rhythm and Heart Failure

location_facility:
University hospital of Bordeaux
University hospital of Nantes
Centre Cardiologique du Nord
University Hospital of Rennes
University hospital of Rouen
Hôpital Saint Louis
Clinique Bizet
Nouvelles Cliniques Nantaises
University hospital La Timone
University hospital of Nancy
University hospital of Lille
University hospital of Montpellier


title: Evaluation of the Efficacy of 3-month Continuous Extended Treatment With Azithromycin in Idiopathic Purulent Oedematous Sinusitis in Adults: a Multicentre Randomised Controlled Trial

acronym: SOPAZITHRO

summary:
Purulent Oedematous Sinusitis (POS) is a particular form of chronic rhinosinusitis observed in 2% of the general population. In spite of its heavy impact on the quality of life, There is no established recommendation for the treatment of primary POS. Long-term low-dose macrolides are currently proposed for these forms of chronic rhinosinusitis when conventional treatments (local corticosteroids, saline rinsing, iterative short courses of antibiotics targeted on pathogens, and surgical opening and drainage) have failed. This treatment with macrolides is currently applied off-label.

This study aims to assess the efficacy of macrolides in POS. An extensive workup is fulfilled to exclude other forms of chronic rhinosinusitis (Th2 biased inflammatory diseases, allergic diseases) (allergy, nasosinusal polyposis) or those due to cystic fibrosis or immune deficiency.

lead_sponsor: Centre Hospitalier Intercommunal Creteil

location_facility: Centre Hospitalier Universitaire De Nantes

location_facility: Hôpitaux Universitaires de Marseille Conception