title: Effects of Regular and Consequent Citrus Fruit Consumption on Vascular Protection Specific Role of the Component Phytomicronutrients

acronym: AGRUVASC

summary:
Epidemiological studies definitively show that fruit and vegetable consumption is positive for health and more specifically for cardiovascular diseases (CVD) prevention. In France, among fruits, those which are the most frequently consumed are citrus fruits essentially as juices and more specifically as orange juices. However, their health effects have been poorly studied so far. Citrus fruits contain vitamin C associated with various phytomicronutrients i.e. carotenoids (essentially -cryptoxanthin) and polyphenols. Each fruit contains specific compounds: hesperetin in orange, naringenin in grapefruit, eriodyctiol in lemon. Some scientific studies performed either in vitro or in animal models demonstrated properties of these micronutrients which could contribute to a positive health effect of citrus fruits on vascular protection. However data are still missing.

The main goal of this project is to characterize the effect of orange juice consumption on vascular disease risk factors and to evaluate the specific role of their micronutrient compounds (polyphenols and carotenoids) in this protection. To reach this goal, a randomized "cross-over" clinical study will be performed on volunteers presenting a mild hypercholesterolemia. They will consume for 4 weeks an orange juice or a reconstituted drink similar to the orange juice for its composition in carbohydrates, minerals, vitamin C and folates but without phytomicronutrients. The effect of the juice consumption on the vascular function will be monitored exploring lipid abnormalities in plasma, measuring endothelial vasoreactivity (FMD) (Flow Mediated Dilatation), as well as endothelial dysfunction, thrombosis, inflammation and oxidative stress biomarkers in plasma. Comparison of urinary metabolomes after orange juice consumption or that of the reconstituted drink will lead to the identification of the metabolic pathways modulated by the orange juice micronutrients.

Moreover ELISA tests for the two major flavanones from citrus fruits (hesperetin and naringenin) will be developed. They will be used to determine the plasma levels of these molecules in order to analyze the relation "ingested quantity - bioavailable quantity - physiological effect".

The results obtained in this project will allow clarifying citrus fruit effects, and particularly orange juice, in vascular protection.

ReferenceCitation: Hertog MG, Feskens EJ, Hollman PC, Katan MB, Kromhout D. Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study. Lancet. 1993 Oct 23;342(8878):1007-11.

ReferenceCitation: Hertog MG, Kromhout D, Aravanis C, Blackburn H, Buzina R, Fidanza F, Giampaoli S, Jansen A, Menotti A, Nedeljkovic S, et al. Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study. Arch Intern Med. 1995 Feb 27;155(4):381-6. Erratum in: Arch Intern Med 1995 Jun 12;155(11):1184.

ReferenceCitation: Knekt P, Jarvinen R, Reunanen A, Maatela J. Flavonoid intake and coronary mortality in Finland: a cohort study. BMJ. 1996 Feb 24;312(7029):478-81.

ReferenceCitation: Yochum L, Kushi LH, Meyer K, Folsom AR. Dietary flavonoid intake and risk of cardiovascular disease in postmenopausal women. Am J Epidemiol. 1999 May 15;149(10):943-9. Erratum in: Am J Epidemiol 1999 Aug 15;150(4):432.

ReferenceCitation: Geleijnse JM, Launer LJ, Van der Kuip DA, Hofman A, Witteman JC. Inverse association of tea and flavonoid intakes with incident myocardial infarction: the Rotterdam Study. Am J Clin Nutr. 2002 May;75(5):880-6.

ReferenceCitation: Leuzzi U, Caristi C, Panzera V, Licandro G. Flavonoids in pigmented orange juice and second-pressure extracts. J Agric Food Chem. 2000 Nov;48(11):5501-6.

ReferenceCitation: Jung HA, Jung MJ, Kim JY, Chung HY, Choi JS. Inhibitory activity of flavonoids from Prunus davidiana and other flavonoids on total ROS and hydroxyl radical generation. Arch Pharm Res. 2003 Oct;26(10):809-15.

ReferenceCitation: Franke AA, Cooney RV, Henning SM, Custer LJ. Bioavailability and antioxidant effects of orange juice components in humans. J Agric Food Chem. 2005 Jun 29;53(13):5170-8.

ReferenceCitation: Lee DH, Gross MD, Jacobs DR Jr; Cardiovascular Risk Development in Young Adults Study. Association of serum carotenoids and tocopherols with gamma-glutamyltransferase: the Cardiovascular Risk Development in Young Adults (CARDIA) Study. Clin Chem. 2004 Mar;50(3):582-8. Epub 2004 Jan 15.

ReferenceCitation: Dwyer JH, Paul-Labrador MJ, Fan J, Shircore AM, Merz CN, Dwyer KM. Progression of carotid intima-media thickness and plasma antioxidants: the Los Angeles Atherosclerosis Study. Arterioscler Thromb Vasc Biol. 2004 Feb;24(2):313-9. Epub 2003 Dec 1.

ReferenceCitation: Aneja R, Hake PW, Burroughs TJ, Denenberg AG, Wong HR, Zingarelli B. Epigallocatechin, a green tea polyphenol, attenuates myocardial ischemia reperfusion injury in rats. Mol Med. 2004 Jan-Jun;10(1-6):55-62.

ReferenceCitation: Hadjadj S, Paul JL, Meyer L, Durlach V, Vergès B, Ziegler O, Drouin P, Guerci B. Delayed changes in postprandial lipid in young normolipidemic men after a nocturnal vitamin A oral fat load test. J Nutr. 1999 Sep;129(9):1649-55.

ReferenceCitation: Constans J, Conri C. Circulating markers of endothelial function in cardiovascular disease. Clin Chim Acta. 2006 Jun;368(1-2):33-47. Epub 2006 Mar 10. Review.

ReferenceCitation: Gorinstein S, Caspi A, Libman I, Lerner HT, Huang D, Leontowicz H, Leontowicz M, Tashma Z, Katrich E, Feng S, Trakhtenberg S. Red grapefruit positively influences serum triglyceride level in patients suffering from coronary atherosclerosis: studies in vitro and in humans. J Agric Food Chem. 2006 Mar 8;54(5):1887-92.

ReferenceCitation: Gorinstein S, Leontowicz H, Leontowicz M, Drzewiecki J, Jastrzebski Z, Tapia MS, Katrich E, Trakhtenberg S. Red Star Ruby (Sunrise) and blond qualities of Jaffa grapefruits and their influence on plasma lipid levels and plasma antioxidant activity in rats fed with cholesterol-containing and cholesterol-free diets. Life Sci. 2005 Sep 23;77(19):2384-97.

ReferenceCitation: Gorinstein S, Leontowicz H, Leontowicz M, Krzeminski R, Gralak M, Delgado-Licon E, Martinez Ayala AL, Katrich E, Trakhtenberg S. Changes in plasma lipid and antioxidant activity in rats as a result of naringin and red grapefruit supplementation. J Agric Food Chem. 2005 Apr 20;53(8):3223-8.

ReferenceCitation: Constans J, Bennetau-Pelissero C, Martin JF, Rock E, Mazur A, Bedel A, Morand C, Bérard AM. Marked antioxidant effect of orange juice intake and its phytomicronutrients in a preliminary randomized cross-over trial on mild hypercholesterolemic men. Clin Nutr. 2015 Dec;34(6):1093-100. doi: 10.1016/j.clnu.2014.12.016. Epub 2014 Dec 26.

lead_sponsor: University Hospital, Bordeaux

location_facility: Hopital Saint André - Service de Médecine Interne - Pathologie Vasculaire

intervention_type: Behavioral


title: Real-world Study on Safety, Effectiveness and Quality of Life of Trastuzumab Deruxtecan in Patients With Metastatic or Unresectable HER2-positive Breast Cancer: a French Ambispective Multicentre 2 Year-follow-up Cohort Study

summary: Collection of data in real life conditions on satefy, effectiveness and quality of life of trastuzumab deruxtecan in patients with metastatic or unresectable HER2-positive breast cancer.

study_start_date_type: Actual

status: Recruiting

study_completion_date_type: Anticipated

study_type: Observational

time_perspective: Other

enrollment_type: Anticipated

lead_sponsor: Daiichi Sankyo France

lead_sponsor_type: industriel

status_simplified: Ongoing


title: Immunotherapy by Nivolumab in Neoadjuvant and Adjuvant Setting in Patients With Advanced HCC Treated by Electroporation in Curative Intent: French Multicenter Phase 2 Therapeutic Trial.

acronym: NIVOLEP

summary:
Percutaneous ablation (PA) is the only non-surgical curative treatment of hepatocellular carcinoma (HCC). Due to its excellent tolerance, particularly in patients with portal hypertension or bearing comorbidities, it now represents in France nearly 70% of the first-line curative treatment of "in Milan" tumours. For HCC less than 3 cm, ideal indication for percutaneous ablations, results of monopolar radiofrequency ablation (mRFA), are excellent with only 5% of reported non-tumoral control after a first procedure .

In addition to mRFA the arsenal of ablations has grown considerably with the emergence of new techniques. They allow the expansion of indications for PA, especially in patients with poor prognostic tumors or relatively advanced beyond the Milan criteria . In this setting, multibipolar mode using no touch technique (mbpRFAnt) increases the tumour volume that can be ablated, allowing the removal of large tumors> 5 cm . Furthermore, electroporation (EP) is a new PA technique that does not promote thermoablation but induce tumoral cells apoptosis and is particularly interesting for difficult-to-treat lesions located near vascular or biliary trunks . Inadequate tumour control is then de facto greater in these situations, around 20% at one year.

The idea of optimizing HCC curative treatments using neoadjuvant or adjuvant biotherapy, particularly in patients with advanced tumors in curative intent, is particularly attractive. One trial in adjuvant setting was conducted, the STORM trial, that tested the benefit of sorafenib in curative intent of in Milan HCC. This negative trial included patients with in Milan HCC, with an expected low rate of recurrence with only few patients treated by PA.

In parallel, the development of new molecules for HCC treatment, especially immunotherapy, seems to give promising results in palliative setting . Furthermore, PA procedures and most likely electroporation induce T-cell recruitement that may foster immunomodulation .

Neoadjuvant and adjuvant trials using these new molecules must now be cautiously designed based on the rigorous selection of special populations and therapeutic indications.

This project proposes a Phase 2 trial testing the safety and efficacy of treatment with Nivolumab in neoadjuvant and adjuvant setting in patients with advanced HCC treated by electroporation in curative intent.

status: Active, not recruiting

study_type: Interventional

primary_purpose: Treatment

enrollment_type: Actual

ReferenceType: background

ReferenceCitation: Sutter O, Calvo J, N'Kontchou G, Nault JC, Ourabia R, Nahon P, Ganne-Carrié N, Bourcier V, Zentar N, Bouhafs F, Sellier N, Diallo A, Seror O. Safety and Efficacy of Irreversible Electroporation for the Treatment of Hepatocellular Carcinoma Not Amenable to Thermal Ablation Techniques: A Retrospective Single-Center Case Series. Radiology. 2017 Sep;284(3):877-886. doi: 10.1148/radiol.2017161413. Epub 2017 Apr 28.

ReferenceCitation: Bruix J, Takayama T, Mazzaferro V, Chau GY, Yang J, Kudo M, Cai J, Poon RT, Han KH, Tak WY, Lee HC, Song T, Roayaie S, Bolondi L, Lee KS, Makuuchi M, Souza F, Berre MA, Meinhardt G, Llovet JM; STORM investigators. Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2015 Oct;16(13):1344-54. doi: 10.1016/S1470-2045(15)00198-9. Epub 2015 Sep 8.

ReferenceCitation: El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, Kim TY, Choo SP, Trojan J, Welling TH Rd, Meyer T, Kang YK, Yeo W, Chopra A, Anderson J, Dela Cruz C, Lang L, Neely J, Tang H, Dastani HB, Melero I. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017 Jun 24;389(10088):2492-2502. doi: 10.1016/S0140-6736(17)31046-2. Epub 2017 Apr 20.

ipd_sharing: No

lead_sponsor: Assistance Publique - Hôpitaux de Paris

intervention_type: Drug

lead_sponsor_type: academique


title: Additive Value of Biological and Electrocardiographic Biomarkers for Risk Stratification in Hypertension

summary:
Risk stratification of hypertensive patients includes assessment of traditional cardiovascular risk factors and subclinical target organ damages particularly left ventricular hypertrophy (LVH).

LVH may routinely screened by transthoracic echocardiography by measuring the left ventricular mass (LVM).

However, transthoracic echocardiography suffers from several pitfalls: poor reproducibility, technical limitations and unavailability at a first evaluation by general practitioners.

Other biomarkers may be particularly helpful in hypertension risk stratification. The amplitude of the R wave in aVL lead is a simple validated ECG parameters of LVH and a strong predictor of cardiovascular events and mortality.

Plasma N-terminal pro Brain Natriuretic Peptide (NT-proBNP) is also strongly related to LVM and is an independent predictor of all-cause mortality in hypertension.

The main objective of our study is to determine the additive prognostic value of R wave in aVL and NT proBNP on all-cause and cardiovascular mortality.

Secondary objectives are to determine the addition prognostic value of NT-proBNP and R wave in aVL combined in comparison to each marker taken into account

This study will include 1600 patients who had a work-up of their hypertension in the Cardiology Department of Croix-Rousse Hospital (Hospices Civils de Lyon, Lyon, France) from January 1997 to January 2014.

Their data will be collected in an Access database; their vital status will be obtained by the INSEE unit CépiDC.

status: Completed

study_completion_date_type: Actual

time_perspective: Retrospective

lead_sponsor: Hospices Civils de Lyon

location_facility: Hospices Civils de Lyon - Hopital de la Croix Rousse

status_simplified: Completed


title: Study of Biomarkers That Predict the Evolution of Huntington's Disease

acronym: BIOHD

summary:
Huntington's disease (HD) is a rare, autosomal dominant, progressive neurodegenerative disorder typically becoming noticeable in middle age. It is clinically characterized by progressive involuntary movements (bradykinesia and hyperkinesia), neuropsychiatric disturbances (depression, irritability), and cognitive impairments progressing to dementia.

The striatum (caudate and putamen) is the primary area of neuronal degeneration in HD. Today, there is no validated curative treatment. HD affects approximately 6 000 patients in France and more than 30 000 individuals are considered at risk for this disease.

While the disease gene is discovered and we are capable to do a predictive genetic diagnosis for asymptomatic patients, there is no clinical or biological way to predict the age of onset or the progressive profile of patients.

One of the fundamental characteristics of this disease is its extreme variability from one patient to other both in terms of their evolution and their onset of action. Thus, this inter-individual variability severely limits the genetic counselling and complicating the neurological assessment.

Increasingly, it has been assumed that modifier genes may be the source of this inter-individual variability and that their identification could help the understanding and prediction of disease progression.

Given that the mutant protein is ubiquitous, the molecular dysfunction of neurons could be found in peripheral cells from the bloodstream and will be more accessible to investigation.

status: Unknown status

time_perspective: Prospective

intervention_type: Other

status_simplified: Unknown


type: Other Identifier

title: Pilot Study: Comparison of Patients' Knowledge of Direct Oral Anticoagulants in Post-hospitalization Between 2 Cardiology Departments Offering or Not a Pharmaceutical Interview During Hospitalization

acronym: EDUC-AOD

summary:
Direct oral anticoagulants (Rivaroxaban, Apixaban and Dabigatran) are an alternative to anti-vitamin K drugs and low molecular weight heparins in many cardiovascular diseases.

This new class of anticoagulants represents a particular and very promising advance: they are administered orally, their mechanism of action is rapid and direct on coagulation and their predictable pharmacological action allows for administration at fixed doses. In contrast to anti-vitamin K, there is no need for routine biological monitoring.

However, their therapeutic range is narrow and there is no routine biological monitoring. Rigorous compliance is therefore necessary. In addition, there are no official validated recommendations either for the measurement of anticoagulant activity in certain emergency situations, or for the management of severe bleeding (except recently for Pradaxa®).

Their correct use requires the training and involvement of health professionals as well as information and support for patients.

Pharmaceutical interviews are one of the main ways in which pharmacists can ensure this security through personalized and optimal patient care.

The purpose of these interviews is to:

Reinforce the pharmacist's advisory, educational and preventive roles with patients;
To enhance the pharmacist's expertise in the area of medication;
To evaluate the patient's knowledge of his or her treatment;
To assess the patient's knowledge of his or her treatment; To seek the patient's therapeutic adherence and help him or her to take ownership of his or her treatment;
To evaluate, in the long term, the patient's appropriation of his or her treatment.

In this way, they enable involvement with patients while providing a link between healthcare professionals, which is essential for optimal patient care.

In recent years, numerous studies have been conducted on pharmaceutical interviews in the United Kingdom and the Netherlands.

On the other hand, few studies have been conducted in France to evaluate the clinical impact of pharmaceutical interviewing in medical services.

The aim of this study is to compare patients' knowledge of direct oral anticoagulants between 2 cardiology departments offering or not a pharmaceutical interview.

ipd_sharing: Undecided

lead_sponsor: Direction Centrale du Service de Santé des Armées

location_facility: Centre Hospitalier Intercommunal de Montreuil


title: Environment and Lung Cancer

acronym: PPE

summary:
Cannabis is the most consumed drug in the world and the French are the main consumers in Europe. The most recognized effects of cannabis on human health are of a neuro-psychic nature. The medical literature on the effects of cannabis on the lung in general, and on lung carcinogenesis in particular, is most often reassuring (Tashkin, Chest 2018; Zhang, Int J Cancer 2015; Ghasemiesfe JAMA Netw. Open. 2019), despite the fact that the concentration of carcinogens in cannabis smoke is higher than that contained in tobacco smoke (Moir, Chem. Res. Toxicol. 2008), and that cannabis smoking has been implicated in the occurrence of ENT cancers. Rather, research focuses on the therapeutic effects of cannabis, especially analgesics, and even on its possible anti-tumor virtues (Abrams, Jama Oncol. 2020). These reassuring data should, however, be viewed with a great deal of caution. On the one hand, the illegal nature of cannabis in most countries and its frequent association with tobacco consumption make studies on the subject difficult and often biased. On the other hand, the daily practice of oncologists, who observe numerous cases of advanced and rapidly progressive lung cancer occurring in young patients who are heavy users of cannabis, raises suspicion of an unrecognized role of cannabis in lung carcinogenesis.

In a preliminary multicenter study on French patients under 50 years of age operated for primary lung cancer (Betser, ERJ 2021), we demonstrated that cannabis consumption was extremely frequent, concerning 43% of patients, but mentioned in patients' medical records only in 4 out of 10 cases, while the smoking status was always noted.

In addition, by comparing people who smoke cannabis (always here associated with tobacco) to patients who only smoke tobacco or to non-smokers, we identified a different profile of lung cancers, with more poorly differentiated tumors, presenting at a more advanced stage (more T3-T4 versus T1-T2) requiring more complex surgery, and mostly located in the upper lobes of the lung.

Similar research work is currently underway at Gustave Roussy (Dr Pradere-Dr Planchard, Villejuif, France) on patients with metastatic lung cancer, with a focus on overall survival and molecular profile.

design_allocation: Non-Randomized

primary_purpose: Health Services Research

lead_sponsor: Centre Chirurgical Marie Lannelongue

location_facility:
Centre Chirurgical Marie Lannelongue
Institut Gustave Roussy


title: Randomized Study Evaluating the Cost Impact and Effectiveness of Systematic Liver Fast-MRI Surveillance for Early-stage Hepatocellular Carcinoma in High-risk Patients Included in Ultrasound Surveillance Programs

acronym: FASTRAK

summary:
Intro: Hepatocellular carcinoma (HCC) is the 6th leading cause of cancer worldwide. In France, more than 10,000 new cases are identified each year. The latter occur in 85% of cases in cirrhosis, the most frequent causes of which are excessive alcohol consumption, metabolic syndrome or HBV/HCV infection. Patients with cirrhosis justify being included in monitoring programs involving the performance of a semi-annual liver ultrasound (US) in order to detect HCC eligible for curative treatment (liver resection or percutaneous ablation). This practice is considered to be cost-effective in the event of an annual incidence of HCC> 1.5%. US in this context has a low sensitivity for the detection of HCC at the very early stage and the following observations have been made in the last 20 years:

The rate of patients detected at early stage BCLC 0 is around 30% by ultrasound
The rate of patients included in surveillance programs detected with advanced HCC eligible for palliative treatment is around 20%
Reducing the periodicity of liver ultrasounds from 6 to 3 months does not improve these results.

In parallel, liver MRI has been evaluated as a tool for the early detection of HCC. Its performance for the detection of HCC at the very early stage exceeds 80%. However, due to the higher cost compared to US, it was estimated that its use in screening context would only be cost effective in the event of an annual incidence> 3%. In addition, the practice of these expensive and long-lasting MRIs (30 to 45 minutes) can be optimized by carrying out abbreviated MRI protocols" or Fast-MRI: short protocols (<10 minutes), based on the sequences with the better detection sensitivities (Se> 83%).

The hypothesis is that Fast-MRI used as a screening examination in patients at high risk of HCC (> 3% per year) could increase the rates of patients detected at an early stage accessible to curative treatment and demonstrate its cost-effectiveness in this population.

Hypothesis/Objective: The main objective is to assess the cost / QALY and / patient detected with an early HCC BCLC 0 (single tumor <2cm) by semi-annual monitoring by liver US and Fast-MRI, compared to conventional semi-annual monitoring by liver US alone in patients with cirrhosis and an anticipated HCC incidence>3%.

Conclusion: If positive, this trial could modify international practice guidelines and set MRI as the optimal tool for early HCC detection in high-risk patients.

study_start_date_type: Anticipated

status: Not yet recruiting

design_allocation: Randomized

primary_purpose: Screening

location_facility: Assistance Publique Hôpitaux de Paris - Hôpital Avicenne


title: The Experiences of Family Caregivers of Stroke Patients: A Cross-sectional Study of a French Cohort

acronym: AVCAIDE

summary:
Stroke is the most common cause of non-traumatic disability in adults and ranks second among causes of dementia and third among causes of death. In France, stroke affects around 140,000 patients each year and entails enormous economic costs. Given the average age of onset of stroke, its prevalence is expected to increase with increasing life expectancy and the advancing age of the population.

Clinically, depending on the region of the brain affected, stroke results in a sudden and abrupt onset of sensorimotor, cognitive, emotional and / or behavioral manifestations, associated with variable recovery from patient to patient. Stroke has psychological, social and family consequences. Indeed, its occurrence could affect patients on a physical and psychological level (direct physical and cognitive sequelae of stroke, decrease or even absence of autonomy and dependence of the entourage, associated psychological changes) and generate repercussions on the dynamics. family or that of the couple (ie, changes in activities, redistribution of tasks, changes or even inversion of roles, alteration of the intimate sphere), as well as professional and social life. This could hamper the quality of life of patients and their loved ones and cause collateral damage to their social or family environment.

After discharge from the hospital, the patient's relatives will play a major role in taking charge of home care (e.g. household activities and personal care around hygiene, food, mobility and administration. treatments) as well as in the community (eg purchase of clothes or food, accompaniment to medical visits), although these helpers do not have the professional knowledge and skills in care. Despite the positive effects that caregivers can have in connection with the care they provide (ie, feeling of accomplishment and usefulness, development of a sense linked to this helping role, better self-esteem, improvement of personal skills), their continued investment in their sick relatives could deprive them of their resources, making them "hidden or invisible patients / victims". In addition, the gap between caregiver capacities to provide care and the health needs of patients could result in caregiver burden (i.e., caregiving burden). Caregivers of stroke patients experience an impaired quality of life, neglect of their own health, reduced work and leisure activities, as well as psychological suffering involving feelings of abandonment, loneliness and helplessness. uncertainty. In the context of a stroke, caregivers may be overwhelmed by the emotions of their ill loved ones as well as their own emotions. Emotional regulation is essential in such a context rich in emotional experience; it is the set of strategies that enables individuals to influence the emotions they feel, when they appear, and how they experience and express them.

Reviews of the literature have highlighted the lack of studies addressing the burden on caregivers and the need for research to identify those at risk and implement appropriate interventions.

No French study has specifically addressed the notion of the burden of caregivers of stroke patients, their coping strategies, their experiences or emotional regulations. This type of study would however constitute a step towards the design and implementation of personalized care (eg: psychotherapies), by strengthening effective / adaptive strategies and modifying those which are less effective / poorly adaptive. This could improve the well-being of caregivers and their sick relatives, and direct health policies to reduce the economic impact of this aid.

ReferenceType: result

ReferenceCitation: Blake H, Lincoln NB. Factors associated with strain in co-resident spouses of patients following stroke. Clin Rehabil. 2000 Jun;14(3):307-14.

ReferenceCitation: Blake H, Lincoln NB, Clarke DD. Caregiver strain in spouses of stroke patients. Clin Rehabil. 2003 May;17(3):312-7.

lead_sponsor: Groupe Hospitalier Paris Saint Joseph

location_facility: Institut de Psychologie, Université de Paris


title: Role of Fluorodeoxyglucose (FDG) PET-CT in the Initial Staging of Breast Cancer (ASAINT 1) and in the Early Assessment of Response to Neoadjuvant Chemotherapy (ASAINT 2)

acronym: ASAINT

summary:
The two main objectives of this prospective study are:

to identify those patients for whom pre-treatment FDG (Fluorodeoxyglucose) PET (positron emission tomography) CT-scan (Computed tomography scan) provides useful information for the treatment of breast cancer (ASAINT 1),
to improve FDG PET-CT-scan imaging criteria for assessing response to neoadjuvant therapy early, in M0-patients (ASAINT 2).

The secondary objective is to better understand the interactions between the imaging parameters of FDG PET-CT-scan and biological and histological features of breast cancer .

This is a non-interventional study. Two PET-CT-scans are performed, one before starting treatment, and the other after 2 cycles of neoadjuvant chemotherapy. The two PET-CT-scans are prescribed by oncologists from the center of breast diseases Unit at St. Louis hospital, in Paris, France. Oncologists provide clear information to the patients on the purpose of the examination. The examinations are performed in the nuclear medicine department at St. Louis hospital. PET-CT-scans data, tumor characteristics, results of other imaging and biological tests, results of surgery and patient's follow-up are summarized in a "de-identified" file. This file has been declared to the National Commission on Informatics and Liberties (CNIL). The data in this file are established prospectively and secondary analyzed to assess the precise role of PET-CT-scans in the initial staging of breast cancer and to determine the optimal PET-CT-scans criteria to evaluate response to neoadjuvant treatment early.


type: EudraCT Number

title: A Randomized, Placebo Controlled, Double Blind, Double Dummy, Multicenter Trial Comparing Electronic Cigarettes With Nicotine to Varenicline and to Electronic Cigarettes Without Nicotine.

acronym: ECSMOKE

summary:
Background:

Electronic cigarettes (EC) mainly containing nicotine (88-95 % of users) are widely and growingly used worldwide. It is estimated that there were 1.7 million daily users in France in 2016. Although the number of publications about its use is increasing exponentially, there are no evidence based, unbiased, head-to-head comparison data about its efficacy as an aid to smoking cessation. As of today, only two head-to-head randomized studies have been published, both reported negative results at the main endpoint but they used first and second generation EC delivering nicotine with low or unknown bioavailability. Recent EC deliver nicotine with largely improved bioavailability.

One of the randomized studies compared EC with and without nicotine to nicotine patch and reported similar smoking cessation rate at main outcome. However, there is no published, double blind study comparing EC use with a well-studied, licensed smoking cessation medication.

Superiority of EC with nicotine compared to EC without nicotine and to a reference smoking cessation medication while collecting also straightforward information about safety, would allow proposing EC with nicotine to the large population of smokers who intend to quit and situate it among the approved smoking cessation treatments.

The clinical study's hypothesis:

EC containing nicotine can be considered as a nicotine replacement therapy having, probably, a better bioavailability of nicotine than the marketed pharmaceutical NRTs, first line medications of smoking cessation. It is therefore of interest to compare EC containing nicotine to EC without nicotine but also to a reference medication with demonstrated efficacy in smoking cessation. We hypothesize that EC with nicotine provides a higher smoking abstinence rate than EC without nicotine and may be as good as varenicline, our reference medication.

ReferenceType: derived

ReferenceCitation: Berlin I, Dautzenberg B, Lehmann B, Palmyre J, Liégey E, De Rycke Y, Tubach F. Randomised, placebo-controlled, double-blind, double-dummy, multicentre trial comparing electronic cigarettes with nicotine to varenicline and to electronic cigarettes without nicotine: the ECSMOKE trial protocol. BMJ Open. 2019 May 24;9(5):e028832. doi: 10.1136/bmjopen-2018-028832.


title: Analysis of Non-vaccination Factors Against Hepatitis B Virus (HBV) in Drug Users Consulting at the Croix-rousse Drug Addict Care Center (Annuaire Centres de Soins, d'Accompagnement et de prévention en Addictologie (CSAPA))

acronym: ANOVAC B

summary:
Hepatitis B is one of the major public health problems in the world. According to World Health Organization (WHO) data, about 2 billion people have been in contact with the hepatitis B virus (HBV), and 257 million have chronic HBV infection.

Although France is a low endemic country, with just over 280,000 people with chronic infection, hepatitis B remains a public health problem due to its morbidity and mortality.

Drug users are a population at risk by their consumption practices (injection or sniffing), but also by other high-risk behaviours, particularly sexual behaviours.

Prevention therefore involves securing consumption practices (sterile and single-use equipment) and protection of sexual intercourse, but also by vaccination (protecting more than 90%).

Since 1982, HAS has recommended to systematically vaccinate drug users. However, according to the Marmottan study published in 2003, immunization coverage among drug addicts was already insufficient in 1999 (45.3%) and decreased again in 2000 and 2001 (15.6 and 21.7%).

This decrease can be explained by the controversy around the potential link, now refuted, between vaccine against HBV and demyelination, which has stopped the mass vaccination campaign launched by the French health authorities in 1995.

A study conducted between 2009 and 2012 on injecting drug users in Alsace, estimated vaccination coverage at 28%.

The hypothesize is that despite the recommendations in a population at high risk of contamination, and a balance of benefits and risks in favor of vaccination, vaccination coverage against the hepatitis B virus remains insufficient among drug users because of poor vaccination acquaintance, and hepatitis B in general, in this population.

Principal objective of this study is to identify non-vaccination factors against hepatitis B virus among drug users consulting at the Croix-Rousse CSAPA.

location_facility: Hôpital de la Croix-Rousse, 103 grande rue de la Croix-Rousse


title: Identification and Validation of Addictology Expert Patients' Fields of Intervention With Inpatients for Addictive Disorders

acronym: HAPEX

summary:
Although there are many publications concerning the benefit of the interventions of the self-help movements and peer health mediators in psychiatry, no studies have described the intervention specific to patients with expertise in addictology (EP), nor evaluated their effectiveness.

The objective of this study is twofold: identify and define the fields of intervention of EPs adapted to the specific needs of addictology patients. And validate, through a pilot study, the intermediate effectiveness of EP intervention. This EP intervention will be built on the areas of expertise defined in the first step. Intermediate effectiveness will be measured by patients' ability to manage their addiction. The first part of the study will consist of a preliminary qualitative patient-centered study to clarify patients' needs and expectations regarding the content of the EPs' intervention into a one addictology service of the university hospital of Bichat, Paris, France. This will make it possible to translate these needs into fields of expertise to address during the EPs' intervention and will result in the creation of a hetero-questionnaire. The second part of the study will consist of a before-and-after comparative study on inpatients who are their own controls based on the hetero-questionnaire constructed through the qualitative study.

This study will identify the main EP's intervention fields in addictology in which EP are more relevant to patients. Thus, their inpatient interventions can be validated and improved, and better carried by addiction professionals.

location_facility: Département psychiatrie et addictologie Bichat Claude Bernard


title: EFFICACY OF THE SLEEVE GASTROPLASTY WITH THE ENDOSCOPIC SYSTEM OVERSTICH SX ON WEIGHT LOSS AND REDUCTION OF CO-MORBIDITY FOR OBESE PATIENTS

acronym: SLEEVE

summary:
The OverStitch ™ Sx System (Apollo Endosurgery Inc., Austin, Tx, Usa) is a new generation of endoscopic suturing device. It is inserted into an endoscope allowing the approximation of Luc Karsentys soft tissue by placement of sutures. It is as effective a suture system as a surgical system. The OverStitch ™ Sx allows suturing in the upper and lower GI with a flexible single channel endoscope. Previously, the ™ Overstich was only compatible with an Olympus dual channel endoscope.

Thus, a wide range of interventions are possible, including gastric endoplastic sleeve (ESG), RYGB revision, anastomotic fistula repair and / or sleeve revision. In each of these indications, the OverStitch (OverStitch) ™ system has shown its effectiveness and safety.

The OverStitch Endoscopic ™ Suture System allows the entire digestive wall to be sutured through a flexible endoscope. Thus, a wide range of interventions are possible, including gastric pocket repair after gastric bypass surgery, anastomotic fistula repair, endoscopic treatment of digestive perforation, and endoscopic sleeve surgery. In each of these indications, the OverStitch system has demonstrated its effectiveness and safety. But this technique is recent, especially in France. In addition, no data has yet been released regarding the new Overstitch ™ Sx device compatible with all single channel endoscopes.

An observational study including patients in French centers that are experts in therapeutic endoscopy seems essential to us to better assess this new device and this new technique in practice

primary_purpose: Other

lead_sponsor: Clinique du Trocadéro

intervention_type: Procedure


title: Quantification of Dopamine Active Transporter (DAT) in Humans: Validation of a New Radiophamaceutical, the [18F] LBT-999

acronym: LBT 999

summary:
Idiopathic Parkinson's disease (IPD) is a degenerative disease affecting the dopaminergic system. Clinical symptoms of IPD commonly begin after the loss of at least 40 to 50% of striatal dopaminergic terminals (specially putaminal terminals).

The Dopamine neuronal transporter (DAT) is a highly expressed protein in the membrane of presynaptic nigrostriatal dopaminergic terminals. The use of a DAT's radioligand in the initial stages of the disease would lead to an early detection of nigral cell loss.

Currently, only one DAT's radioligand has obtained marketing authorization in France, the 123I-FPCIT, for use in Single Photon Emission Computed Tomography (SPECT).

Otherwise, the Positron Emission Tomography (PET), a more sensitive technology than SPECT with higher resolution has become for a few years the new gold standard for visual analysis and quantification of neurotransmission systems (including the dopaminergic system).

A DAT tracer labelled with Carbon 11 ([11C] PE2l) have been developed and is currently used as a reference in various research centers.

However, in order to enable a clinical use of this tracer (which currently can't be because of the too short period of Carbon 11), the unit INSERM U930 "Imaging and Brain" in collaboration with the CERRP (Center for Studies and Research on Radiopharmaceuticals) developed a new version of this tracer, labelled with 18-fluor: the [18F] LBT-999.

The main goal of this study is to compare the [18F] LBT-999 uptake between a group of patients suffering from a Parkinsonien syndrome to a group healthy volunteers.

status: Terminated

primary_purpose: Diagnostic

ReferenceCitation: Agid Y. Parkinson's disease: pathophysiology. Lancet. 1991 Jun 1;337(8753):1321-4. Review.

ReferenceCitation: Brooks DJ, Pavese N. Imaging biomarkers in Parkinson's disease. Prog Neurobiol. 2011 Dec;95(4):614-28. doi: 10.1016/j.pneurobio.2011.08.009. Epub 2011 Aug 30. Review.

ReferenceCitation: Brooks DJ. Imaging dopamine transporters in Parkinson's disease. Biomark Med. 2010 Oct;4(5):651-60. doi: 10.2217/bmm.10.86. Review.

ReferenceCitation: Chalon S, Hall H, Saba W, Garreau L, Dollé F, Halldin C, Emond P, Bottlaender M, Deloye JB, Helfenbein J, Madelmont JC, Bodard S, Mincheva Z, Besnard JC, Guilloteau D. Pharmacological characterization of (E)-N-(4-fluorobut-2-enyl)-2beta-carbomethoxy-3beta-(4'-tolyl)nortropane (LBT-999) as a highly promising fluorinated ligand for the dopamine transporter. J Pharmacol Exp Ther. 2006 Apr;317(1):147-52. Epub 2005 Dec 9.

ReferenceCitation: de Rijk MC, Tzourio C, Breteler MM, Dartigues JF, Amaducci L, Lopez-Pousa S, Manubens-Bertran JM, Alpérovitch A, Rocca WA. Prevalence of parkinsonism and Parkinson's disease in Europe: the EUROPARKINSON Collaborative Study. European Community Concerted Action on the Epidemiology of Parkinson's disease. J Neurol Neurosurg Psychiatry. 1997 Jan;62(1):10-5.

ReferenceCitation: Fernagut PO, Li Q, Dovero S, Chan P, Wu T, Ravenscroft P, Hill M, Chen Z, Bezard E. Dopamine transporter binding is unaffected by L-DOPA administration in normal and MPTP-treated monkeys. PLoS One. 2010 Nov 22;5(11):e14053. doi: 10.1371/journal.pone.0014053.

ReferenceCitation: Hsiao IT, Weng YH, Lin WY, Hsieh CJ, Wey SP, Yen TC, Kung MP, Lu CS, Lin KJ. Comparison of 99mTc-TRODAT-1 SPECT and 18 F-AV-133 PET imaging in healthy controls and Parkinson's disease patients. Nucl Med Biol. 2014 Apr;41(4):322-9. doi: 10.1016/j.nucmedbio.2013.12.017. Epub 2014 Jan 10.

ReferenceCitation: Sérrière S, Tauber C, Vercouillie J, Guilloteau D, Deloye JB, Garreau L, Galineau L, Chalon S. In vivo PET quantification of the dopamine transporter in rat brain with [¹⁸F]LBT-999. Nucl Med Biol. 2014 Jan;41(1):106-13. doi: 10.1016/j.nucmedbio.2013.09.007. Epub 2013 Oct 8.

ReferenceCitation: Schillaci O, Pierantozzi M, Filippi L, Manni C, Brusa L, Danieli R, Bernardi G, Simonetti G, Stanzione P. The effect of levodopa therapy on dopamine transporter SPECT imaging with( 123)I-FP-CIT in patients with Parkinson's disease. Eur J Nucl Med Mol Imaging. 2005 Dec;32(12):1452-6. Epub 2005 Sep 8.

ReferenceCitation: Sharma S, Moon CS, Khogali A, Haidous A, Chabenne A, Ojo C, Jelebinkov M, Kurdi Y, Ebadi M. Biomarkers in Parkinson's disease (recent update). Neurochem Int. 2013 Sep;63(3):201-29. doi: 10.1016/j.neuint.2013.06.005. Epub 2013 Jun 19. Review.

ReferenceCitation: Snow BJ, Tooyama I, McGeer EG, Yamada T, Calne DB, Takahashi H, Kimura H. Human positron emission tomographic [18F]fluorodopa studies correlate with dopamine cell counts and levels. Ann Neurol. 1993 Sep;34(3):324-30.

ReferenceCitation: Varrone A, Stepanov V, Nakao R, Tóth M, Gulyás B, Emond P, Deloye JB, Vercouillie J, Stabin MG, Jonsson C, Guilloteau D, Halldin C. Imaging of the striatal and extrastriatal dopamine transporter with (18)F-LBT-999: quantification, biodistribution, and radiation dosimetry in nonhuman primates. J Nucl Med. 2011 Aug;52(8):1313-21. doi: 10.2967/jnumed.111.089953. Epub 2011 Jul 15.

lead_sponsor: University Hospital, Tours


title: Comparison of the Efficacy and Tolerance of Triple Therapy Guided by the PCR Detection of Clarithromycin Resistance WITH Empiric Concomitant Quadruple Therapy for Helicobacter Pylori Infection: a Randomised Multicentre Trial

acronym: Hepysé

summary:
The H pylori infection remains a public health problem. The eradication rate with the first line triple therapy (PPI-amoxicillin-clarithromycin) is insufficient (estimated at 70%) due to the frequency of resistance to clarithromycin, which reaches 21% in France. Until now,European and French consensus recomended tofavor sequential therapy (5 days PPI-amoxicillin and 5 days PPI-clarithromycin-metronidazole) or quadruple bismuth therapy ( 10 days PPI-tetracyclin,-metronidazole- bismuth). Studies in countries with low prevalence of clarithromycin resistance reported eradication rate of 85% with sequential therapy and reported a low impact of clarithromycin resistance on the effectiveness of this treatment. However, recent studies suggest a greater impact of clarithromycin resistance. Recent meta-analysis shows that empiric sequential therapy is less efficacious than concomitant quadruple therapy. Therefore, recent Maastricht V / Florence meeting October 7-8 2015) recommended to abandon sequential therapy and to favor 14 days concomitant therapy in first line in order to reach an eradication rate >90%.

In a multicenter randomized clinical trial (HELICOSTIC 2010-2011 AO ICST 2009), we compared a triple therapy guided by the results of a PCR test that detects resistance to clarithromycin and levofloxacin (HelicoDR ®) to empirical triple therapy (PPI-amoxicillin-clarithromycin). 1384 patients and among them 526 infected patients were enrolled in 10 centers. The results in 415 patients were 73.1% for the empirical treatment versus 85.5% (p <0.001) for the treatment guided by PCR HelicoDR®. This study also demonstrated the limits of the test HelicoDR®: onerous, possibility of contamination, little practical contribution of the determination of resistance to quinolones.

Moreover, it has been shown that triple therapy efficiency could be optimized by increasing duration up to 14 days and increasing dose of PPI to 40mg b.d;.and eradications rates > 90% were reported with susceptible to clarithromycin strains.

Adverse events are less common with optimized triple therapy than with concomitant quadruple therapy.

The main objective is to compare the efficacy of optimized triple therapy guided by the results of a PCR test (eradication rates 90% hypothesized) with quadruple concomitant therapy (eradication rate 90% hypothesized).

The secondary objective is to determine side effects of optimized guided triple therapy as well as the quadruple concomitant therapy in France.


title: Impact of a Telemonitoring Program on the Rate of Hospitalizations for Worsening of Cardio-respiratory Symptoms in COPD Patients Treated at Home by Long-term Non-invasive Ventilation (NIV): a Randomized Controlled Trial

summary:
COPD is characterized by non-reversible chronic airway obstruction. Its evolution is punctuated by successive exacerbations precipitating the progression of the disease and its co-morbidities. The most severe exacerbations are the source of frequent hospitalizations that strongly affect the patient's quality of life and are associated with increased mortality. The diagnosis of exacerbation is mainly clinical but patients frequently consult their doctor too late which may lead to delays in care. However, the early detection and management of these exacerbations can reduce their impact and in particular avoid hospitalization or shorten their duration.

In France, long term Non-Invasive Ventilation (NIV) is a widely used treatment modality in COPD patients with chronic alveolar hypoventilation who have frequent exacerbations. The investigators have demonstrated in a previous study that the analysis of parameters from software embedded in the NIV device can reliably predict the occurrence of an exacerbation. The investigators hypothesize that the daily transmission via a telemonitoring platform of the ventilation parameters of patients, together with an ad hoc warning system, would reduce the rate of hospitalization for COPD patients treated at home with NIV thanks to the early detection and early treatment of these exacerbations.

The purpose of the study is to compare if a program of telemonitoring using the parameters stored by the NIV impact the rate of hospitalization for worsening of cardiorespiratory symptoms in COPD patients versus standard care over a one year period.

primary_purpose: Prevention

lead_sponsor: University Hospital, Grenoble


title: The CINSARC Genomic Signature as a Predictor of Resectability of High Grade Serous Ovarian Adenocarcinomas

acronym: OVASARC

summary:
The majority of primary cancers of the ovary or peritoneum are represented by high-grade serous adenocarcinomas. These are rare pathologies, the incidence of which is estimated at 7.1 per 100,000, representing approximately 4,500 new cases per year in France (INCA 2017). In the absence of effective screening, nearly 85% of patients have an advanced disease at diagnosis (corresponding to the FIGO III or IVA stage, characterized by diffuse peritoneal involvement). Despite multidisciplinary care, the majority of patients (80%) will recur within a median of 18 to 24 months.

It is therefore necessary to develop new tools, in particular molecular, in order to allow :

to better select patients accessible to full interval surgery
to exclude patients who would not benefit from this surgery in terms of survival

In 2010, Chibon et al. identified, from a cohort of patients with soft tissue sarcoma (STM), a molecular signature (called CINSARC), based on the expression profile of 67 genes involved in mitotic control and chromosomal integrity. The team showed that this transcriptomic signature is an independent prognostic factor in different types of STM, but also a prognostic factor more discriminating than the histological grade (FNCLCC), historical and major prognostic factor of STM.

Being initially made from frozen material and on a DNA biochip (Affymetrix), this signature was unusable outside the field of fundamental research. This is why CINSARC has been gradually optimized, first by the RNA sequencing technique on frozen tissue fixed in formalin (FFPE), and recently on FFPE tissue by the NanoString® technique. This very sensitive and inexpensive technique requires only small amounts of total RNA, making it compatible with use on "routine" diagnostic samples, microbiopsy or surgical biopsy, opening the door to real clinical application. Several clinical studies using this latest CINSARC optimization (called NanoCind®) to determine the treatment of patients with STM will also begin soon.

As a result of this work, necessary in order to more precisely support the potential of CINSARC in this pathology, the investigators hope to be able to assess from the diagnosis the evolutionary potential of the patients, which could make it possible to evaluate therapeutic strategies adapted to the profiles of each subpopulation: the investigators can for example imagine in theory a therapeutic de-escalation for low-risk patients, or else, for very high-risk patients, an intensified strategy.

lead_sponsor: Institut Claudius Regaud

location_facility: Institut Claudius Regaud Institut Universitaire du cancer Toulouse Oncopole


title: Mobility and Quality of Life in Community Ambulators With Knee Locking Deficiency Using a Microprocessor Controlled Knee Ankle Foot Orthosis and a Stance Control Orthosis: Randomized Crossover Trial

summary: The purpose of this multicentric study is to assess the impact of C-BRACE on mobility, endurance, confidence, participation, satisfaction, psychosocial adjustment and quality of life in community ambulators using a Stance Control Orthosis.

ReferenceCitation: Deems-Dluhy S, Hoppe-Ludwig S, Mummidisetty CK, Semik P, Heinemann AW, Jayaraman A. Microprocessor Controlled Knee Ankle Foot Orthosis (KAFO) vs Stance Control vs Locked KAFO: A Randomized Controlled Trial. Arch Phys Med Rehabil. 2021 Feb;102(2):233-244. doi: 10.1016/j.apmr.2020.08.013. Epub 2020 Sep 22.

ReferenceCitation: Karatzios C, Loiret I, Luthi F, Leger B, Le Carre J, Saubade M, Muff G, Benaim C. Transcultural adaptation and validation of a French version of the Prosthetic Limb Users Survey of Mobility 12-item Short-Form (PLUS-M/FC-12) in active amputees. Ann Phys Rehabil Med. 2019 May;62(3):142-148. doi: 10.1016/j.rehab.2019.02.006. Epub 2019 Apr 6.

ReferenceCitation: Chatman AB, Hyams SP, Neel JM, Binkley JM, Stratford PW, Schomberg A, Stabler M. The Patient-Specific Functional Scale: measurement properties in patients with knee dysfunction. Phys Ther. 1997 Aug;77(8):820-9.

ReferenceCitation: Demers L, Monette M, Descent M, Jutai J, Wolfson C. The Psychosocial Impact of Assistive Devices Scale (PIADS): translation and preliminary psychometric evaluation of a Canadian-French version. Qual Life Res. 2002 Sep;11(6):583-92.

ReferenceCitation: Middleton A, Fritz SL, Lusardi M. Walking speed: the functional vital sign. J Aging Phys Act. 2015 Apr;23(2):314-22. doi: 10.1123/japa.2013-0236. Epub 2014 May 2. Review.

ReferenceCitation: Probsting E, Kannenberg A, Zacharias B. Safety and walking ability of KAFO users with the C-Brace(R) Orthotronic Mobility System, a new microprocessor stance and swing control orthosis. Prosthet Orthot Int. 2017 Feb;41(1):65-77. doi: 10.1177/0309364616637954. Epub 2016 Jul 10.

ReferenceCitation: Schmalz T, Probsting E, Auberger R, Siewert G. A functional comparison of conventional knee-ankle-foot orthoses and a microprocessor-controlled leg orthosis system based on biomechanical parameters. Prosthet Orthot Int. 2016 Apr;40(2):277-86. doi: 10.1177/0309364614546524. Epub 2014 Sep 23.

ReferenceCitation: Filiatrault J, Gauvin L, Fournier M, Parisien M, Robitaille Y, Laforest S, Corriveau H, Richard L. Evidence of the psychometric qualities of a simplified version of the Activities-specific Balance Confidence scale for community-dwelling seniors. Arch Phys Med Rehabil. 2007 May;88(5):664-72.

ReferenceCitation: Andrade LF, Ludwig K, Goni JMR, Oppe M, de Pouvourville G. A French Value Set for the EQ-5D-5L. Pharmacoeconomics. 2020 Apr;38(4):413-425. doi: 10.1007/s40273-019-00876-4.

lead_sponsor: Otto Bock France SNC

location_country: Germany France

location_facility:
Chu Rangueil
CRRF La Tourmaline
CRRF Léopold Bellan
Centre Jacques Calvé Fondation Hopale
HIA Percy
Katholisches Klinikum Koblenz-Montabaur
PFH Private Hochschule Göttingen
CRF Korian Le Mont Veyrier
IRR Louis Pierquin
CRRF La Chataigneraie
Centre Bouffard Vercelli
Pôle de Réadaptation de Cornouaille
Hia Laveran
Hôpital Raymond-Poincaré
IRMA Institut Robert Merle d'Aubigné
Centre Hospitalier Dieppe
CRF Salies de Béarn
LADAPT Thionis

intervention_type: Device


title: Multi-centre Prospective Cohort of Childhood Leukaemia: Determinants of Health and Quality of Life of the Patients After Treatment for an Acute Leukaemia During Childhood or Adolescence - LEA

summary: Regular advances in cancer treatment have dramatically improved the prognosis of children and adolescents with acute leukemia (AL), raising with a great acuity the problem of the late physical side effects, social integration, quality of life of the patients and their family as well as identification of the determinants of these outcomes. Large nationwide and international cohorts developed in general population (I4C, EPIC ELF…) are restricted to the study of childhood cancers occurrence. In addition, the national registries (French, European) of childhood cancers are designed to evaluate incidence and mortality, but not to produce individual detailed data on the follow-up and outcome of these children. Answering these questions supposes a comprehensive multidisciplinary approach resting on prospective cohorts of cancer survivors, specifically exploring the outcome of these children. These cohorts allow to identify prognostic factors of the health condition and social integration, and to propose adapted strategies of follow-up. The Childhood Cancer Survivor Study (CCSS), which remains the most important study, only concerns the North-American populations and rests on a self-reported follow-up assessment. In France, the LEA study, initiated in 2004 could answer some of these questions, but the representativeness and the size of the population (study initially limited to two areas PACA-Corsica and Lorraine) remain insufficient to study uncommon events. Similar approaches are conducted in Europe trough the broad collaborative Pancare network, to which the LEA program is associated.

ReferenceCitation: Oudin C, Berbis J, Bertrand Y, Vercasson C, Thomas F, Chastagner P, Ducassou S, Kanold J, Tabone MD, Paillard C, Poirée M, Plantaz D, Dalle JH, Gandemer V, Thouvenin S, Sirvent N, Saultier P, Béliard S, Leverger G, Baruchel A, Auquier P, Pannier B, Michel G. Prevalence and characteristics of metabolic syndrome in adults from the French childhood leukemia survivors' cohort: a comparison with controls from the French population. Haematologica. 2018 Apr;103(4):645-654. doi: 10.3324/haematol.2017.176123. Epub 2018 Jan 19.

ReferenceCitation: Saultier P, Auquier P, Bertrand Y, Vercasson C, Oudin C, Contet A, Plantaz D, Poirée M, Ducassou S, Kanold J, Tabone MD, Dalle JH, Lutz P, Gandemer V, Sirvent N, Thouvenin S, Berbis J, Chambost H, Baruchel A, Leverger G, Michel G. Metabolic syndrome in long-term survivors of childhood acute leukemia treated without hematopoietic stem cell transplantation: an L.E.A. study. Haematologica. 2016 Dec;101(12):1603-1610. Epub 2016 Aug 11.

ReferenceCitation: Oudin C, Auquier P, Bertrand Y, Chastagner P, Kanold J, Poirée M, Thouvenin S, Ducassou S, Plantaz D, Tabone MD, Dalle JH, Gandemer V, Lutz P, Sirvent A, Villes V, Barlogis V, Baruchel A, Leverger G, Berbis J, Michel G. Late thyroid complications in survivors of childhood acute leukemia. An L.E.A. study. Haematologica. 2016 Jun;101(6):747-56. doi: 10.3324/haematol.2015.140053. Epub 2016 Mar 11.

lead_sponsor: Assistance Publique Hopitaux De Marseille

location_facility: Assistance Publique Hopitaux de Marseille

intervention_type: Biological


title: Efficacy and Tolerance of RHEOpheresis in the Treatment of Peripheral Artery Disease in Hemodialysis Patients: a Prospective Randomized Single-blind Trial

acronym: RHEO-PAD

summary:
Peripheral arterial disease (PAD) with limb-threatening ischemia (PAD-LTI) involves both macrocirculation and microcirculation. Macrocirculatory abnormalities are accessible to revascularization techniques (endovascular or surgical) contrary to microcirculatory abnormalities. Conservative treatments have limited efficacy in patients with end-stage renal disease (ESRD). There is no alternative treatment for patients with PAD-LTI in hemodialysis.

Rheopheresis is an apheresis technique specifically designed for the treatment of microcirculatory disorders in which anomalies of rheology are at the center of physiopathology. This double cascade plasma filtration technique reduces plasma viscosity and eliminates inflammation mediators which play an essential role in PAD. This technique has already shown its effectiveness in a randomized trial in dry Age-related macular degeneration (AMD), another pathology of microcirculation. The effectiveness of rheopheresis in PAD-LTI has only been reported in a small number of cases.

This Hypothesis is that the treatment of microcirculation by rheopheresis would improve wound healing of the ischemic lesion and/or reduce major amputation and thus the prognosis of the affected limb of the patient with PAD-LTI in hemodialysis. This objective is to demonstrate the efficacy of rheopheresis, (twelve sessions), to avoid major amputation and reaches complete wound healing of ischemic lesion in the dialysis patient population with PAD-LTI. This study is prospective, Controlled, Parallel, Randomized, Single blind and Multicentric in France (12 French centers).

location_facility: Assistance Publique Hôpitaux de Marseille


title: Added Value of Supersonic Shear Imaging in the Diagnosis of White Matter Damage in Preterm Infants

acronym: BELUGA

summary:
Preterm birth and perinatal events related can interrupt microscopic maturation of the developing white matter leading to diffuse injury and subsequent neurocognitive impairments. Brain maturation can be studied using diffusion tensor imaging but is difficult to assess early after birth, repeatedly and at the bedside. Supersonic Shear wave Imaging (SSI) could be of interest in this clinical setting. This technique, already investigated in adults (breast, thyroid or liver fibrosis staging), has not been yet evaluated in neonates.

Objective:

To describe the feasibility and reproducibility of quantitative elasticity mapping in preterm infants and to correlate to gestational age.

Methods:

SSI is a quantitative stiffness imaging technique based on the combination of a remote palpation induced into tissues by the radiation force a focused ultrasonic beam and an ultrafast ultrasound imaging sequence. Such ultrafast frame rates permit to track in real time the displacements induced by the propagation of the resulting shear waves. For each pixel, the shear wave speed can be estimated locally and enables quantitative mapping of the local shear elasticity (characterizing the stiffness in kPa). In this study, we will use a new generation of ultrafast ultrasound scanners (Aixplorer®, Supersonic Imagine, Aix en Provence, France) with a linear L10-2 probe (256 elements, 6 MHz) in neonates born between 25 and 40 weeks' gestation (n=100). Three separate acquisitions will be obtained for each area of interest both on right and left sides and stiffness was measured using a unique ROI of 2.5 cm².


title: Randomized Trial Comparing the Efficacy of Chlorambucil to Fludarabine in Patients With Advanced Waldenström Macroglobulinemia,Lymphoplasmacytic Lymphoma or Splenic Marginal Zone Lymphoma

summary:
Waldenström's macroglobulinaemia (WM) is a lymphoproliferative disorder characterized by a monoclonal IgM paraprotein and morphological evidence of lymphoplasmacytic lymphoma: the cells are IgM+, IgD+, CD19+ and CD20+ but usually CD5-, CD10- and CD23-. The treatment efficacy is difficult to assess because of the lack of clear diagnostic criteria , good response criteria, and of randomized trials.

The actual treatment is Chlorambucil, an alkylating agent. A purine analogue such as Fludarabine has proven its efficacy on 30 % to 80 % as first line therapy

This study is a phase II b open, prospective, international multicenter trial (England, Dr Johnson, Dr Catovsky, Australia: Dr Seymour) promoted by the French Cooperative Group on Chronic Lymphoid Leukemia in untreated WM, or closely related disorders ( Lymphoplasmacytic lymphoma or splenic marginal zone lymphoma). 366 patients must be included, among them 180 patients in France. Patients will be stratified according to the lymphoproliferative disorder.

The patients will receive Chlorambucil by oral route for 10 days every 28 days (12 cycles) (8 MG/M², 6 MG/M² if patient is more than 75 years old) or Fludarabine by oral route for 5 days every 28 days (6 cycles) (40MG/M², 30 MG/M² if patient is more than 75 years old).

The primary objective is to compare the efficacy (response rate) of Chlorambucil to Fludarabine in previously untreated patients. The secondary objectives are the duration of response, the improvement of hematological parameters, the toxicity, the quality of life, the event free survival and the overall survival.

ReferenceCitation: Leblond V, Johnson S, Chevret S, Copplestone A, Rule S, Tournilhac O, Seymour JF, Patmore RD, Wright D, Morel P, Dilhuydy MS, Willoughby S, Dartigeas C, Malphettes M, Royer B, Ewings M, Pratt G, Lejeune J, Nguyen-Khac F, Choquet S, Owen RG. Results of a randomized trial of chlorambucil versus fludarabine for patients with untreated Waldenström macroglobulinemia, marginal zone lymphoma, or lymphoplasmacytic lymphoma. J Clin Oncol. 2013 Jan 20;31(3):301-7. doi: 10.1200/JCO.2012.44.7920. Epub 2012 Dec 10.

ReferenceCitation: Nguyen-Khac F, Lambert J, Chapiro E, Grelier A, Mould S, Barin C, Daudignon A, Gachard N, Struski S, Henry C, Penther D, Mossafa H, Andrieux J, Eclache V, Bilhou-Nabera C, Luquet I, Terre C, Baranger L, Mugneret F, Chiesa J, Mozziconacci MJ, Callet-Bauchu E, Veronese L, Blons H, Owen R, Lejeune J, Chevret S, Merle-Beral H, Leblondon V; Groupe Français d'Etude de la Leucémie Lymphoïde Chronique et Maladie de Waldenström (GFCLL/MW); Groupe Ouest-Est d'étude des Leucémie Aiguës et Autres Maladies du Sang (GOELAMS); Groupe d'Etude des Lymphomes de l'Adulte (GELA). Chromosomal aberrations and their prognostic value in a series of 174 untreated patients with Waldenström's macroglobulinemia. Haematologica. 2013 Apr;98(4):649-54. doi: 10.3324/haematol.2012.070458. Epub 2012 Oct 12.

lead_sponsor: French Study Group on Chronic Lymphoid Leukemia

location_facility: Hôpital La Pitié-Salpêtrière. 47-83 Bd de l'hôpital


title: Impact of Iron Infusion in Anemic Patients on Their Postoperative Outcome After Colorectal Surgery

summary:
In 2005, colorectal surgery in France represented nearly 40,000 procedures per year, of which 80% were scheduled and 70% were for carcinological purposes. Overall postoperative mortality was estimated at 3.4%, morbidity at 35% and average length of stay at 18 days. In addition, the number of newly diagnosed cases of colorectal cancer was 44,872 in 2017, making it the second leading cause of cancer in women and the third in men. The implementation of colorectal Enhanced Rehabilitation After Surgery (EARS) programs has resulted in a significant reduction in length of stay due to an approximately 50% decrease in postoperative complication rates and a faster return of patients to independence. However, despite the integration of RASC into routine practice, morbidity remains high with an estimated complication rate of 15-20%. The persistence of a high complication rate despite the rehabilitation measures can be explained in part by factors present preoperatively that impair postoperative recovery, such as the existence of comorbidities, low functional capacity, the presence of martial or nutritional deficiencies or glycemic imbalance. Links between the presence of these different "deficits", which may coexist, and postoperative morbidity and mortality have already been shown.

Anemia is common in preoperative colorectal surgery and affects approximately one in two patients with cancer. In case of preoperative anemia, the frequency of postoperative complications and the length of stay are increased. Under these conditions, preoperative correction of anemia could facilitate postoperative recovery and reduce the incidence of postoperative complications. In colorectal cancer, anemia is the consequence of an absolute martial deficiency due to iron losses from bleeding and a functional martial deficiency due to decreased availability of iron for erythropoiesis due to inflammation. Correction of preoperative anemia is usually based on 2 types of molecules: iron and erythropoiesis stimulating agents. Erythropoiesis-stimulating agents are not recommended to correct anemia in cancer patients not receiving chemotherapy. Iron can be given orally or intravenously. Intravenous administration is more effective than oral administration in patients with colorectal cancer to correct preoperative anemia. In patients undergoing colon cancer surgery outside of a RAAC program, preoperative iron infusion appears to decrease the incidence of postoperative complications, improve the quality of postoperative recovery, and reduce length of stay. These gains do not appear to be related to correction of preoperative anemia, since preoperative intravenous iron increases hemoglobin levels by only 0.8 g/dl, on average. And, insufficiently to reduce the rate of postoperative transfusion in abdominal or general surgery. Also, the benefits observed with preoperative iron infusion seem to be more related to the direct effects of iron on cardiac and skeletal muscle than by correction of anemia. Since 2016, all patients undergoing scheduled colorectal surgery at the Paris Saint Joseph Hospital Group benefit from the application of a RAAC program. If we do not take into account patients who die during hospitalization (≈ 2%) and patients transferred to Follow-up and Rehabilitation Care (SSR) (≈15%), the impact of the application of a RAAC program is easily measured with the length of stay. Indeed, reducing the frequency of postoperative complications and improving the speed of postoperative recovery translates into reduced lengths of stay. Today, the average length of stay for all patients undergoing colorectal surgery at Saint Joseph Hospital is 7.5 days. The length of stay is longer (8.7 days) in patients with anemia preoperatively compared to those without anemia (7 days). Since 2017, anemic patients scheduled for colorectal surgery, have received intravenous iron infusion preoperatively at Paris Saint Joseph Hospital.

ReferenceCitation: Greco M, Capretti G, Beretta L, Gemma M, Pecorelli N, Braga M. Enhanced recovery program in colorectal surgery: a meta-analysis of randomized controlled trials. World J Surg. 2014 Jun;38(6):1531-41. doi: 10.1007/s00268-013-2416-8. Review.

ReferenceCitation: Muñoz M, Laso-Morales MJ, Gómez-Ramírez S, Cadellas M, Núñez-Matas MJ, García-Erce JA. Pre-operative haemoglobin levels and iron status in a large multicentre cohort of patients undergoing major elective surgery. Anaesthesia. 2017 Jul;72(7):826-834. doi: 10.1111/anae.13840. Epub 2017 Apr 6.


acronym: PARTOSURE-OI

summary:
Prematurity is the leading cause of mortality and perinatal morbidity. Despite the many preventive measures and use of tocolytic therapy, the incidence of premature births has not decreased in recent decades. In 2010 the preterm birth rate (single child, born alive) was still 5.5% in France and 11% in the population of Reunion. In 50% of cases, premature birth is related to spontaneous premature labor layout without rupture of amniotic membranes, called threat of premature birth.The threat of premature birth, defined by the combination of cervical modifications and regular and painful uterine contractions from 22 weeks of amenorrhea and 36 weeks of amenorrhea + 6days, is the major cause of hospitalization in pathological pregnancies services. But all threat of premature delivery situations do not cause premature delivery. In our service, only 30% of patients hospitalized for threat of premature delivery give birth prematurely in accordance with published international data. The diagnosis of threat of premature delivery is difficult and it is still not possible to differentiate a "false labour" of a "real labour".

Currently the diagnosis of threat of premature delivery in routine is based on the combination of vaginal examination, the ultrasound, cervical length, but this strategy lacks specificity.

In absence of prognostic tool for predicting more reliably the risk of premature delivery in situation of threat of premature delivery, the medical cares are maximalist.: hospitalization, conducting paraclinical investigations, prescription of tocolytics treatments and conducting antenatal corticotherapy. it seems particularly necessary to identify more efficient prognostic criteria that the clinic and ultrasound for judging the severity of threat of premature delivery in other words to predict the risk of premature delivery to adapt and adjust the care of patients after diagnosis of threat of premature delivery.

lead_sponsor: Centre Hospitalier Universitaire de la Réunion


title: Clinical Phenotyping and Characterization of Neural Networks and Cognitive Processes Involved in Mental Retardation X-linked

acronym: XLMR

summary:
X-linked Mental retardation (XLMR) represent 10% of the causes of mental retardation with a prevalence in both sexes around 1/296, i.e. 3.3 / 1000 births (Opitz et al., 1986). This heterogeneous group of XLMR includes dozens of rare diseases, some of them affecting only a few patients. Molecular diagnosis is currently available in France for 25 XLMR genes, within the national network of XLMR molecular diagnosis. However, whereas some syndromes such as Fragile X syndrome, are now well clinically defined, this is not the case for recently identified syndromes for which very few data is available, preventing clinicians to focus molecular diagnosis on a specific gene.

Therefore, this study aims to :

Achieve a description of the clinical phenotype specific to each XLMR gene (Phase 1 of the study, n=200)
Characterize the cognitive learning mechanisms and dysfunctional neural networks involved (Phase 2 of the study, n=75, i.e. 5 groups of 15 patients with a mutation in the same gene). These two elements constitute key steps to develop appropriate rehabilitation strategies and targeted pharmacological therapies.

Moreover, the impact of mental retardation on the primary caregiver within the family and the induced burden in terms of psycho-social, organizational and economic burden will also be assessed. These elements, directly related to the patient's environment, are very important to characterize in order to better understand the consequences of each gene mutation (Phase 3 of the study, n=283). For example, it is necessary to better understand the impact of Fragile X syndrome in terms of capacity and behavior, lifestyle, and health care needs of the patients While advancing knowledge allows to consider innovative therapeutics, the implementation of these therapeutics and assessment of their impact on the patients' life trajectory, require precise characterization of the population to be treated in medico socioeconomic terms.

location_facility: Groupement Hospitalier Est - Hôpital Femme Mère Enfant - Service de neurologie pédiatrique


title: Toward a Real-time Access to Sleepers' Mental Content

acronym: SleepDance

summary:
Sleep is crucial for global cognitive functioning, but its exact functions and mechanisms are still poorly understood. Cognitive studies of sleep typically rely on linking electrophysiological changes measured during sleep with behavioral and neural changes collected in tasks performed during wakefulness. What concomitantly happens in the mind of sleeping subjects is often ignored, certainly because it is virtually inaccessible. Yet, major advances in the understanding of human behaviors have resulted from an integrated approach that combines both neural and cognitive measures of their ongoing mental processes. The goal of this study is to provide real-time measures of the cognitive processes occurring within sleep.

To prompt real-time access to the sleeping mind, investigators will use auditory stimulation in people with unique sleep peculiarities: sleepwalkers whose overt behaviours may enable to objectively visualize ongoing cognitive processes during non-REM (NREM) sleep.

location_facility: Service des Pathologies du Sommeil, Hôpital Pitié-Salpétrière


acronym: TRAAP

title: Tranexamic Acid for Preventing Postpartum Haemorrhage Following a Vaginal Delivery: a Multicenter Randomised Double Blind Placebo Controlled Trial

lead_sponsor: University Hospital, Angers

source: euctr

ReferenceCitation: Novikova N, Hofmeyr GJ. Tranexamic acid for preventing postpartum haemorrhage. Cochrane Database Syst Rev. 2010 Jul 7;(7):CD007872. doi: 10.1002/14651858.CD007872.pub2. Review. Update in: Cochrane Database Syst Rev. 2015;6:CD007872.

ReferenceCitation: Peitsidis P, Kadir RA. Antifibrinolytic therapy with tranexamic acid in pregnancy and postpartum. Expert Opin Pharmacother. 2011 Mar;12(4):503-16. doi: 10.1517/14656566.2011.545818. Epub 2011 Feb 4. Review.

ReferenceCitation: Sentilhes L, Daniel V, Darsonval A, Deruelle P, Vardon D, Perrotin F, Le Ray C, Senat MV, Winer N, Maillard F, Deneux-Tharaux C. Study protocol. TRAAP - TRAnexamic Acid for Preventing postpartum hemorrhage after vaginal delivery: a multicenter randomized, double-blind, placebo-controlled trial. BMC Pregnancy Childbirth. 2015 Jun 14;15:135. doi: 10.1186/s12884-015-0573-5.

ReferenceCitation: Sentilhes L, Lasocki S, Ducloy-Bouthors AS, Deruelle P, Dreyfus M, Perrotin F, Goffinet F, Deneux-Tharaux C. Tranexamic acid for the prevention and treatment of postpartum haemorrhage. Br J Anaesth. 2015 Apr;114(4):576-87. doi: 10.1093/bja/aeu448. Epub 2015 Jan 8. Review.

ReferenceCitation: Sentilhes L, Winer N, Azria E, Sénat MV, Le Ray C, Vardon D, Perrotin F, Desbrière R, Fuchs F, Kayem G, Ducarme G, Doret-Dion M, Huissoud C, Bohec C, Deruelle P, Darsonval A, Chrétien JM, Seco A, Daniel V, Deneux-Tharaux C; Groupe de Recherche en Obstétrique et Gynécologie. Tranexamic Acid for the Prevention of Blood Loss after Vaginal Delivery. N Engl J Med. 2018 Aug 23;379(8):731-742. doi: 10.1056/NEJMoa1800942.

summary: The purpose of this study is to assess whether the administration of a low dose of tranexamic acid just after vaginal delivery can reduce the incidence of immediate postpartum hemorrhage, in women who receive a prophylactic administration of oxytocin.


title: Assessment of the Efficacy of Early Intrauterine Tamponade With a Belfort-Dildy Balloon Obstetric Tamponade System in the Treatment of Immediate Postpartum Hemorrhage

acronym: TUB

summary: The purpose of this study is to evaluate the impact of early intrauterine tamponade with a Belfort-Dildy balloon catheter in immediate postpartum hemorrhage(IPPH) after vaginal delivery and refractory to first-line uterotonic treatment, ie performed at the same time as second line uterotonic treatment, as compared tolate intrauterine tamponade performed in case of failure of second line uterotonic treatment, on the final severity of PPH. ).

ReferenceCitation: Laas E, Bui C, Popowski T, Mbaku OM, Rozenberg P. Trends in the rate of invasive procedures after the addition of the intrauterine tamponade test to a protocol for management of severe postpartum hemorrhage. Am J Obstet Gynecol. 2012 Oct;207(4):281.e1-7. doi: 10.1016/j.ajog.2012.08.028. Epub 2012 Aug 17.

ReferenceCitation: Georgiou C. Balloon tamponade in the management of postpartum haemorrhage: a review. BJOG. 2009 May;116(6):748-57. doi: 10.1111/j.1471-0528.2009.02113.x. Review.

ReferenceCitation: Tindell K, Garfinkel R, Abu-Haydar E, Ahn R, Burke TF, Conn K, Eckardt M. Uterine balloon tamponade for the treatment of postpartum haemorrhage in resource-poor settings: a systematic review. BJOG. 2013 Jan;120(1):5-14. doi: 10.1111/j.1471-0528.2012.03454.x. Epub 2012 Aug 13. Review.

ReferenceCitation: Revert M, Cottenet J, Raynal P, Cibot E, Quantin C, Rozenberg P. Intrauterine balloon tamponade for management of severe postpartum haemorrhage in a perinatal network: a prospective cohort study. BJOG. 2017 Jul;124(8):1255-1262. doi: 10.1111/1471-0528.14382. Epub 2016 Oct 25.

ReferenceCitation: Kellie FJ, Wandabwa JN, Mousa HA, Weeks AD. Mechanical and surgical interventions for treating primary postpartum haemorrhage. Cochrane Database Syst Rev. 2020 Jul 1;7:CD013663. doi: 10.1002/14651858.CD013663.


title: Time to Surgery and Survival Outcomes for Patients With Resected Colorectal Carcinoma: Multicenter Study (BIG RENAPE)

acronym: DELARC

summary:
Colorectal cancer (CRC) is diagnosed in one million patients each year worldwide and is the 2nd leading cause of cancer death. Peritoneal metastasis (MP) is seen in 10% of CRC patients and is the metastatic site with the worst prognosis.

Complete cytoreduction surgery (CCS) is the only treatment that allows for prolonged survivals. Five-year overall survival (OS) after CCS ranges from 30% to 60% compared with 0 to 5% with exclusive medical treatment.

Chemotherapy (CT) with fluoropyrimidine and oxaliplatin and/or irinotecan 3 months pre-operatively and 3 months adjuvant is widely used. The benefits of perioperative CT have been demonstrated in another resectable metastatic site, the liver and has become by extension a therapeutic standard in France for CRC MPs. However, the impact of delay in the initiation of surgery and adjuvant or neoadjuvant CT is unknown for CRC MPs.

Several deleterious oncologic effects are related to a long period without treatment between

Neoadjuvant chemotherapy and surgery:
Surgery and adjuvant chemotherapy.

Several meta-analyses have demonstrated, for at least 13 different cancers, a continuous association between delays in treatment (CT, radiotherapy, or surgery) and cancer mortality. For CRC, Hanna's meta-analysis showed that for every 4-week delay in adjuvant surgery or CT, the risk of cancer death increased by 6 and 13%, respectively.

These long delays between CT and excisional surgery also decrease survival in patients with liver metastases from colorectal origins and MPs from ovarian origins but this has never been evaluated in patients with MPs from colorectal origins.

Demonstrating an oncologic impact of therapeutic delays would have several strategic practical impacts such as:

Promoting pre- and post-operative rehabilitation programs to facilitate recovery and reduce time to retreatment.
To use more easily techniques (protective stoma, multi-stage surgery) limiting the risk of complications and therefore the delays in treatment.
Propose clinical research protocols aimed at reducing these delays with knowledge of plausible statistical hypotheses.

A therapeutic strategy of shortening the time between each treatment therefore deserves to be evaluated in metastatic forms of colorectal cancer.

The investigators would like to evaluate the hypothesis that shortened time between treatments could have a prognostic impact on recurrence-free survival.

lead_sponsor: Institut Cancerologie de l'Ouest

location_facility:
CHU LYON
Institut de Cancerologie de L'Ouest


title: Lung Transplantation for Pleuroparenchymal Fibroelastosis : a French Multicentric Retrospective Study

summary: This retrospective observational study will evaluate the outcomes of lung transplantation for a rare cause of interstitial lung disease called pleuroparenchymal fibroelastosis. Data will be collected from all transplantation center in France.

location_facility:
Bichat Claude Bernard Hospital, APHP
Marie Lannelongue Hospital
Hopital Louis Pradel
Foch Hospital


type: Registry Identifier

title: Comparison of Prevention Bacterial Inhalation of Patients on Mechanical Ventilation by Using Endotracheal Tube Balloon Polyvinyl Chloride or Polyurethane

acronym: Top-cuff

summary: A number of techniques have been recommended for the prevention of ventilator acquired pneumonia (VAP). These techniques - such as patient positioning, continuous sub-glottic suction of the secretions, selective decontamination of the digestive tract etc… - aim at prevent the inhalation of oro-pharyngeal contaminated secretions around the cuff of the tracheal tube used for connecting the patient to the machine. Their efficacy has been regularly challenged and they are still unable to suppress totally the occurrence of VAP. The cuff of the tracheal tube used for long-term MV in the ICU is most often a low pressure high volume polyvinyl chloride (PVC) cuff in order to adhere to a large surface of the tracheal wall without inducing ischemic lesions. Recent advances allowed industrial companies to provide us with 1) polyurethane cuffs and 2) cuffs with a conic shape, both potentially offering a better tightness against inhalation at least in VITRO and in animal models. The effect on the reduction of VAP incidence has been suggested by several pilot series. The aim of the present project is to assess the efficacy of four types of cuffs (PVC with a conic or a cylinder shape and polyurethane with a conic or a cylinder shape) to prevent tracheal colonisation. We shall measure both oro-pharyngeal and tracheal colonisation during the hours and days following intubation. This will be done in 600 ICU patients of four university affiliated centres from France and Tunisia divided in 64 cluster randomized groups. The results of this research will confirm (or not) the rationale to perform a larger study designed specifically to address the impact on VAP.

ReferenceCitation: Misset B, Timsit JF, Dumay MF, Garrouste M, Chalfine A, Flouriot I, Goldstein F, Carlet J. A continuous quality-improvement program reduces nosocomial infection rates in the ICU. Intensive Care Med. 2004 Mar;30(3):395-400. Epub 2003 Dec 12.

ReferenceCitation: Koenig SM, Truwit JD. Ventilator-associated pneumonia: diagnosis, treatment, and prevention. Clin Microbiol Rev. 2006 Oct;19(4):637-57.

ReferenceCitation: Garrouste-Orgeas M, Chevret S, Arlet G, Marie O, Rouveau M, Popoff N, Schlemmer B. Oropharyngeal or gastric colonization and nosocomial pneumonia in adult intensive care unit patients. A prospective study based on genomic DNA analysis. Am J Respir Crit Care Med. 1997 Nov;156(5):1647-55.

ReferenceCitation: Dullenkopf A, Schmitz A, Frei M, Gerber AC, Weiss M. Air leakage around endotracheal tube cuffs. Eur J Anaesthesiol. 2004 Jun;21(6):448-53.

ReferenceCitation: Lucangelo U, Zin WA, Antonaglia V, Petrucci L, Viviani M, Buscema G, Borelli M, Berlot G. Effect of positive expiratory pressure and type of tracheal cuff on the incidence of aspiration in mechanically ventilated patients in an intensive care unit. Crit Care Med. 2008 Feb;36(2):409-13.

ReferenceCitation: Philippart F, Gaudry S, Quinquis L, Lau N, Ouanes I, Touati S, Nguyen JC, Branger C, Faibis F, Mastouri M, Forceville X, Abroug F, Ricard JD, Grabar S, Misset B; TOP-Cuff Study Group. Randomized intubation with polyurethane or conical cuffs to prevent pneumonia in ventilated patients. Am J Respir Crit Care Med. 2015 Mar 15;191(6):637-45. doi: 10.1164/rccm.201408-1398OC.


title: Assessment of Nephrotoxicity Associated to Parenchymal Clamping During Partial Nephrectomy Using a Microdialysis Technique: NECPAR Study

acronym: NECPAR

summary:
Surgery plays a central role in kidney cancer management being the only therapy that offers the possibility of healing the patients. Currently, the partial nephrectomy is a standard technique because it meets the principle of nephron sparing surgery. A partial nephrectomy requires a control of the renal blood flow using a clamp, which can be parenchymal or vascular (pedicular). In France, most of the centers use pedicular clamping. It is well established that this technique results in warm ischemia of the entire healthy parenchyma and can lead to permanent kidney damages. Currently, no study evaluated the impact of parenchymal clamping on the healthy parenchyma.

The aim of the investigators study is to evaluate the nephrotoxicity of the healthy parenchyma due to parenchymal clamping during partial nephrectomy. This assessment will be done through a microdialysis technique. The microdialysis probe is directly implanted in the healthy unclamped parenchyma and will allow us to measure in real time, during the surgery, the biological changes related to anaerobic metabolism of renal interstitial space. All those measures will be completed by urinary and plasmatic assessments. Oxidative stress will be assessed using four markers of tubular viability : Interleukin 18 (IL18), Kidney Injury Molecule-1 (KIM-1), Neutrophil Gelatinase-Associated Lipocalin (NGAL) and cystatin C and four parameters of anaerobic metabolism : lactate, pyruvate, glycerol and glucose.

This is a prospective pilot study limited to 10 patients included over 12 months. Depending on the results, it will be further developed by a second study comparing parenchymal with pedicle clamping.

lead_sponsor: Centre Hospitalier Universitaire de Saint Etienne


title: Effet du Mepolizumab Sur la décroissance de la corticothérapie systémique Chez Des Patients Avec un Asthme éosinophilique sévère Etude Observationnelle, Suivi de Cohorte Via Une ATU Nominative

acronym: Mepolizumab

summary:
The primary objective of the study is to measure the effect of mepolizumab on declines in oral corticosteroid therapy (prednisolone or prednisone) in patients with severe eosinophilic asthma.

Asthma is a chronic inflammatory disease of the airways that affects 5 to 10% of adults and children. Despite current treatments that are often effective, 10% of patients are not controlled by inhaled therapies. These severe asthma require regular use of systemic corticosteroids in 30 to 40% of cases. In this context, the use of glucocorticoids is associated with many more or less serious adverse effects, but still affecting the patient's quality of life. Several treatments have already been proven to save systemic steroids (theophylline, anti-leukotrienes, golimumab ...). On the other hand, none is currently recommended because of a risk / benefit ratio that is too high.

Mepolizumab is a human monoclonal antibody that binds to and inactivates interleukin 5. It has recently been shown to be effective in reducing the daily dose of oral corticosteroids and in reducing exacerbations in these patients with severe eosinophilic asthma. It also reduces the number of eosinophils in the blood and sputum and improves the quality of life.

Patients will receive a subcutaneous injection of 100mg mepolizumab every 4 weeks for one year, for a total of 12 injections.

In France, this treatment was subject to a Temporary Authorization for Nominative Use in severe eosinophilic asthma and is reserved for hospital use.

The injections will be done in HDJ Pneumology CHU Grenoble Alpes and patients will be followed monthly during injections and one month after the end of injections.

ReferenceCitation: Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON, Yancey SW, Ortega HG, Pavord ID; SIRIUS Investigators. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014 Sep 25;371(13):1189-97. doi: 10.1056/NEJMoa1403291. Epub 2014 Sep 8.

ReferenceCitation: Ortega HG, Liu MC, Pavord ID, Brusselle GG, FitzGerald JM, Chetta A, Humbert M, Katz LE, Keene ON, Yancey SW, Chanez P; MENSA Investigators. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014 Sep 25;371(13):1198-207. doi: 10.1056/NEJMoa1403290. Epub 2014 Sep 8. Erratum in: N Engl J Med. 2015 Apr 30;372(18):1777.


title: Study of the Academic and Professional Course of Narcoleptic Patients (NARCOSCOL-NARCOVITAE)

summary:
Narcolepsy is a chronic, disabling, and rare sleep disorder (prevalence 1/2500) characterized by excessive daytime sleepiness and, in some patients, falls in muscle tone related to emotions (cataplexies). It often begins in childhood or in young adults. Symptoms of narcolepsy are responsible for an important handicap in everyday life, and are often misunderstood by the family and professional environment. In addition, many comorbidities are associated with narcolepsy, such as depression, anxiety, or obesity.

Few studies have investigated the impact of narcolepsy on patients' academic background, socio-professional integration, and quality of life.

Narcoleptic patients may experience more difficulties in their academic and professional path than non-narcoleptic people. These difficulties would be multifactorial (related to the disease itself, comorbidities, external factors ...).

As a better understanding of these determinants could help to inform patients and guide them in their choices, this study propose to establish a comprehensive inventory of educational and professional trajectories of narcoleptic patients in France in order assess the specificity of the difficulties encountered by the people concerned in their life course and to appreciate the attitude of the academic and professional circle with respect to the disease.

This category 3 study (according to the French law "Loi Jardé") is based on the case-control model and will be conducted in all National Reference and Competence Centers for Narcolepsy and Hypersomnia. It will include a population of adult and paediatric patients. It will answer questions about work and schooling in these patients.

time_perspective: Cross-Sectional

location_facility: Centre de Médecine du Sommeil et des Maladies respiratoires - Centre Hospitalier de la Croix Rousse - Hospices Civils de Lyon


title: The State of Play in Picardy of the Knowledge of the Elderly at Risk of Falling at Home in Terms of Prevention and Evaluation.

acronym: Epic-SaPE

summary:
In 2010, the French population over 75 years of age was 9%; It will be 13% in 2030 and 19% in 2050 according to estimates. The incidence of falls is high in the elderly population, with at least one fall per year for one-third of the over-65s and for half of the over-80s. These data are consistent with the international medical literature, particularly in Japan, the United States and France, with a high rate of recurrence from the first fall. Falling is a complex phenomenon that is of great importance in terms of morbidity and mortality since it can be followed by serious complications: failure to recover, recurrences, trauma (fractures, hematomas, wounds), complications of decubitus and ulcers, Immobilization, loss of autonomy, hospitalization, institutionalization, psychological complications (post-fall syndrome, depressive syndrome), death.

Fall risk factors are well known and described and relayed by learned societies of geriatrics and medical literature. In addition, HAS reported on this issue in 2009.

The French Society of Geriatrics and Gerontology (SFGG) defines fragility as a clinical syndrome that reflects a decrease in reserve physiological capacities that alters the coping mechanisms of stress. Its clinical expression is modulated by comorbidities and psychological, social, economic and behavioral factors. Frailty syndrome is a risk marker for mortality and pejorative events, including disability, falls, hospitalization and institutionalization. The fall and its complications are closely related to the fragility syndrome. The very fragile patient must take an active part in his own care. He is the first advocate of fall prevention.

On the other hand medical desertification and the low number of geriatricians makes this implication problematic even more so if the person is isolated or has cognitive impairment. Nevertheless, it is important to make the patient actor of his own prevention. This is the first study to describe the knowledge of older adults about their own risk of falling.

lead_sponsor: Centre Hospitalier Universitaire, Amiens


title: Impact of M184V on the Virological Efficacy to Lamivudine/Dolutegravir

acronym: LAMRES

summary:
In view of the prolongation of patients living with HIV's life expectancy, the question of optimization of ART, which is still a life-long treatment, becomes central. While most patients achieve virological success, their treatments often need to be optimized in order to limit adverse events, drugs interactions and to improve adherence. The switch to dual regimen strategies represent one of the approaches for treatment optimization. Indeed, dual therapy regimens have shown non-inferior efficacy vs triple therapy as simplification therapy and more recently also as first line therapy. From the real-life data it emerges that today in simplification strategies, the dual regimen therapies are prescribed even in patients with a history of virological failure. Circulating HIV-1 resistant variants can be archived in viral reservoirs, where they can persist for years and can reemerge in case of therapeutic selective pressure. In particular, previous selection of M184V may have an impact on virological response to 3TC/DTG. There are few data on a direct comparison of 3TC/DTG efficacy in patients harboring or not harboring the M184V. So, there is a need to assess the efficacy of 3TC/DTG in patients with past M184V mutation in a large set of patients followed in clinical setting.

Thus, the investigators propose a retrospective study of patients with HIV-RNA ≤50 copies/mL who were switched to 3TC/DTG in order to compare the virological efficacy of 3TC/DTG in patients with and without a history of M184V detection in a previous resistance genotype. This study aimed to analyze 800 patients switched to DTG/3TC in clinical real setting in large European (France, Italy, Spain) database.

lead_sponsor: Association de Recherche en Virologie et Dermatologie


title: Central Control of Breathing in Patients With Chronic Obstructive Pulmonary Disease: Identification and Dynamics With Cerebral Functional Magnetic Resonance Imaging

acronym: CHAOSBOLD

summary: Chronic obstructive pulmonary disease (COPD) is a chronicle inflammatory disease with a non reversible diminution of the airway flow. COPD is caused most commonly from tobacco smoking, which triggers an abnormal inflammatory response in the lung. Worldwide, COPD ranked as the sixth leading cause of death in 1990. It is projected to be the fourth leading cause of death worldwide by 2030 due to an increase in smoking rates and demographic changes in many countries. COPD is responsible for 16000 deaths per year in France, 100 000 hospitalizations per year and the health care expenditure of COPD in France is 3.5 billion of Euros. Classical markers of the disease severity, the forced expiratory volume in one second, poorly correlates with dyspnea and prognosis. Therefore, many studies focused on the control of breathing in an attempt to understand the pathophysiological mechanisms involved in the progression of the disease. Breathing control is enhanced in patients with COPD due to the progressive failure of respiratory muscles (airflow obstruction, static and dynamic hyperinflation, positive intrinsic end expiratory pressure), the ventilation/ perfusion ratio abnormalities leading to the loss of the gaz exchange efficiency. Inspiratory command depends on the medulla automatic pathway and the voluntary corticospinal command. Indirect method of breathing control estimation suggested in COPD patients an increased excitability of neurons involved in the voluntary diaphragm activation and a reduced cortical reserve. This may represent an increase risk factor for acute respiratory failure. Until now, no study reported the central breathing control with cerebral fMRI in COPD patients.

primary_purpose: Supportive Care

lead_sponsor: Assistance Publique - Hôpitaux de Paris


title: The French Cohort and Biobank of Devic's Neuromyelitis Optica and Related Neurological Disorders (NMOSD) (NOMADMUS)

acronym: NOMADMUS

summary:
Devic's neuromyelitis optica (NMO) is rare. Epidemiological and demographic data are poor, based mainly on monocentric cohorts. Moreover, NMO might be difficult to distinguish from multiple sclerosis and begin with atypical or incomplete clinical presentations. Therefore, NMO is still underdiagnosed. The constitution of a nationwide and prospective cohort, including not only NMO but also clinical syndromes suggestive of a first episode (DNMO-spectrum disorders (SDs)), should allow to gather a critical mass of cases and answer questions that could not have been addressed at the level of a single centre.

Objectives: The main objective is to describe the clinical, radiological and biological features of NMO spectrum disorder (NMO, isolated longitudinally extensive transverse myelitis (LETM), relapsing or not; isolated atypical optic neuritis (ON)) and their evolution. The second aim is to create a biobank dedicated to NMO (serum, whole blood for RNA and DNA extraction, cerebrospinal fluid), to promote translational research in the field. Methods: NOMADMUS is a prospective, multicentre, observational study of patients NMOSD and related disorder in France. Prevalent cases are included retrospectively and then followed prospectively. Incident cases are included from disease onset and followed prospectively. A minimal set of data has been defined and synthesized on specific paper forms derived from the European database for multiple sclerosis (EDMUS) forms. Patients are systematically tested regarding their AQP4-IgG and MOG-IgG status. All the data are centralised in a EDMUS-derived database in Lyon, the EDEN software. All cases are validated and classified by an expert committee.

lead_sponsor: Hospices Civils de Lyon

location_facility: Hospices Civils de Lyon / Hopital Neurologique Pierre Wertheimer