title: TOTEM RRMS : TestOsterone TreatmEnt on Neuroprotection and Myelin Repair in Relapsing Remitting Multiple Sclerosis

acronym: TOTEM-RRMS

summary:
Centra nervous system (CNF) damage in multiple sclerosis (MS), are mainly attributed to myelin destruction, axonal abnormalities and subsequent degeneration, and are responsible for serious deficiencies. Current therapies are focused on the treatment of inflammation with several types of anti-inflammatory agents. However, there is an urgent need for innovative therapies promoting neuroregeneration and particularly myelin repair.

It has been demonstrated that testosterone can act through neural androgen receptors to promote proliferation and differentiation of oligodendrocyte precursors into mature oligodendrocytes in a cuprizone-induced animal model of demyelination. The rare clinical trials on testosterone are mainly exploratory. Here, we sought to demonstrate an effect of testosterone supplementation in testosterone-deficient patients in a multicenter, randomized, parallel-group, double-blind, placebo-controlled phase 2 trial.

The main objective will be to determine the neuroprotective and remyelinating effects of testosterone using tensor diffusion imaging techniques and thalamic atrophy analyzes.

As secondary objectives, we would like to study the impact of testosterone supplementation on other conventional and unconventional MRI parameters and on clinical outcomes (cognition, fatigue, quality of life, impact on work / activity and anxiety / depression).

ReferenceCitation: Metzger-Peter K, Kremer LD, Edan G, Loureiro De Sousa P, Lamy J, Bagnard D, Mensah-Nyagan AG, Tricard T, Mathey G, Debouverie M, Berger E, Kerbrat A, Meyer N, De Seze J, Collongues N. The TOTEM RRMS (Testosterone Treatment on neuroprotection and Myelin Repair in Relapsing Remitting Multiple Sclerosis) trial: study protocol for a randomized, double-blind, placebo-controlled trial. Trials. 2020 Jun 29;21(1):591. doi: 10.1186/s13063-020-04517-6.

lead_sponsor: University Hospital, Strasbourg, France

location_facility:
CHRU de Strasbourg
CHU de Rennes/Pontchaillou
Hôpital Pitié-Salpêtrière
CHU de Besançon
CHU Nancy

region: Grand Est

nom_etablissement: HOPITAUX UNIVERSITAIRES DE STRASBOURG

acronyme: TOTEM-RRMS

titre: Traitement de la sclérose en plaques récurrente-rémittente par la testostérone : Effets potentiels sur neuroprotection et la remyélinisation

nom_porteur: KREMER

prenom_porteur: Laurent Daniel


title: A Randomized Phase III Clinical Trial to Evaluate the Feasibility and Clinical Relevance of Liquid Biopsy in Patients With Suspicious Metastatic Lung Cancer

acronym: LIBELULE

summary:
Lung cancer is diagnosed at metastatic stage in 60% of the cases. For these patients, first-line treatment is based on histology and molecular characterization of non-squamous non-small cell lung cancer (NSCLC). Thus, quality and quantity of tumor tissue are crucial to determine the appropriate treatment (targeted therapies, chemotherapy and immunotherapy).

However, in routine practice, tissue quality and quantity can be limited (25%), resulting in the need for tumor rebiopsy for molecular analysis. Therefore, lung cancer patients often experience substantial delays before treatment initiation that may be associated with worse patient experience of subsequent cancer care and poorer clinical outcomes.

"Liquid biopsies" (LB) are used to detect genomic alterations in cell-free circulating DNA (cfDNA). Since very recently, they are routinely used in reference centers for the detection of EGFR-mutations when tissue is not sufficient for molecular characterization. Importantly, the feasibility and clinical relevance of systematic liquid biopsies in routine practice has never been evaluated in patients with suspicious advanced lung cancer.

Investigators hypothesize that using systematic LB in patients with clinical suspicion of metastatic lung cancer may reduce time-to-treatment initiation and avoid tissue rebiopsy.

Investigators performed a retrospective study including 250 NSCLC patients treated in a tertiary Cancer Center and in the University Hospital of Lyon, France. The mean time-to-appropriate frontline treatment initiation (TTI) was 42+/-22.5 days. With the use of LB at the time of first consultation, the investigators believe it is possible to reduce the mean TTI down to 33 days (21% reduction in TTI) in the overall population with suspicious metastatic lung cancer, including a 50% and 40% reduction in TTI for EGFR/ALK/ROS1/BRAF V600E subgroups and KRAS/LKB1/ERBB2/c-MET/BRAF non V600E subgroups, respectively.

Investigators therefore designed a "real-life" randomized study to evaluate the feasibility and clinical relevance of LB to decrease the TTI, which may in turn improve patients' outcome. Genomic analyses of circulating cfDNA will be performed using a robust and highly sensitive technology (InVision®), that profiles the presence of genomic aberrations in a panel of 35 genes including mutations, insertion/deletions and rearrangements, including all actionable alterations required to initiate the appropriate first-line therapy (EGFR-, ALK-, ROS1 and BRAF V600E).

study_start_date_type: Actual

status: Completed

study_completion_date_type: Actual

study_type: Interventional

design_allocation: Randomized

primary_purpose: Diagnostic

enrollment_type: Actual

lead_sponsor: Centre Leon Berard

location_facility: Institut de Cancérologie Lucien Neuwirth

location_facility: Groupe Hospitalier de la région de Mulhouse et Sud-Alsace

intervention_type: Diagnostic Test

lead_sponsor_type: academique

status_simplified: Completed


type: Other Identifier

title: An Incitative Multifaceted PROcedure for Pneumococcal Vaccination at the Emergency Department; A Multicenter Prospective Randomized Open Trial The IMPROVED Project

acronym: IMPROVED

summary:
Background :

Community-acquired pneumonia (CAP) is a threat in industrialized countries. It represents the 6th cause of death. CAP also frequently associates with other disorders responsible for admission and death. Among bacteria responsible for CAP, Streptococcus pneumonia is a major pathogen that is commonly involved and frequently leads to severe infection and admission. Categories at risk for this pathogen have been determined, and can be proposed anti-pneumococcal vaccination (APV) that efficiently and safely protects from this microorganism.

In the context of US health services, monocenter pilot experiences have reported improvement of pneumococcal prophylaxis implementing vaccination procedure at ED. A study that set in New Mexico (2003) reported a significant increase in APV (from 18% to 84%) when patients at risk were proposed vaccination at ED. To obtain these results, medical students were specifically trained and dedicated to screen and vaccinate against St. pneumoniae. Another single center trial (Tennessee, 2007) for APV at ED obtained an improvement (from 38.8 to 45.4%) when physicians were alerted for pneumococcal risk by the software they usually utilized at bedside. However these experiences remain sparse as additional dedicated resources are required or patients and attending ED physicians can be reluctant to proceed to vaccination at ED.

Mobile phone and derived communication modalities are current vectors to deliver information in several fields including education and medicine. Initially used in developing countries, short-message services (SMS) have improved behaviour of patients in various medical areas. In France, the investigators have observed that most patients above 50 years of age admitted after ED visit are equipped with mobile phone and can receive alerts by SMS.

These observations prompt us to propose a multifaceted procedure to improve APV after ED visit in at-risk patients, combining structured oral interview, written information and SMS as reminders.

Purpose : The investigators hypothesized that

a multifaceted intervention to promote anti-pneumococcal vaccination combining a structured oral interview, a written information to patient and his/her general practitioner, and a series of 3 SMS,
improves anti-pneumococcal vaccination at 6 months,
in at-risk patients (65+ years) visiting the emergency department. In order to answer this question, the investigators designed an interventional prospective multicenter randomized study (cluster).

study_type: Observational

time_perspective: Prospective

ipd_sharing: No

lead_sponsor: Centre Hospitalier Princesse Grace

collaborators:
Centre Scientifique de Monaco
Pfizer

sponsor_collaborators:
Centre Hospitalier Princesse Grace
Centre Scientifique de Monaco
Pfizer

location_country: Monaco France

location_facility: Centre Hospitalier Universitaire de Clermont-Ferrand

location_facility: Centre Hospitalier Universitaire de Nice


title: Interest in Programming Caesarean Section at 38 Weeks of Pregnancy With Antenatal Betamethasone to Prevent Neonatal Respiratory Distress and to Avoid Emergency Caesarean Section Before Planned Date.

summary:
Comparison of two randomized group :

caesarean section planned at 38 weeks after 2 antenatal injections of 12 mg of betamethasone 48 h before.
caesarean section planned at 39 weeks without corticosteroid.

The aim is to demonstrate that programming caesarean section at 38 weeks of pregnancy, after antenatal corticosteroid, allows to avoid caesarean section in emergency (because of a labour before 39 weeks), without increasing the neonatal respiratory distress rate.

primary_purpose: Prevention

location_facility:
Centre Hospitalier de Haguenau
Cmco-Sihcus
Hôpital de Hasenrain
Le Parc Centre pour la Mère et l'Enfant
Hôpital de Hautepierre

intervention_type: Drug


title: Use of RDS MultiSense® in Post-ICU Patients in the COVID-19 Era

acronym: MONIREA

summary: In this clinical study, the investigators will compare vital parameters measurements obtained using continuous data from reference monitors and continuous wireless MultiSense® monitoring patch in 60 post-ICU (Intensive Care Unit) patients and over 7 days.

status: Recruiting

study_completion_date_type: Anticipated

primary_purpose: Other

enrollment_type: Anticipated

ReferenceType: derived

ReferenceCitation: Pamuk K, Turan N. The effect of light on sleep quality and physiological parameters in patients in the intensive care unit. Appl Nurs Res. 2022 Aug;66:151607. doi: 10.1016/j.apnr.2022.151607. Epub 2022 Jun 26.

oa_host_type: closed

repositories_concat: closed

publisher_dissemination: Elsevier

lead_sponsor: IHU Strasbourg

sponsor_collaborators:
IHU Strasbourg
Rhythm Diagnostic Systems

location_facility: Anesthesia, Critical Care & Perioperative Medicine, Hautepierre

intervention_type: Other

status_simplified: Ongoing


type: EudraCT Number

title: An Open, Prospective, Single Arm Study Investigating Efficacy and Safety of Human Hepatitis B Immunoglobulin Zutectra in Liver Transplanted Patients - the ZEUS Study

acronym: ZEUS

summary:
Patients who receive liver transplantation for hepatitis B virus (HBV) induced liver failure require longterm therapy to prevent HBV reinfection of the transplanted liver. The approved preventative treatment is a combination of antihepatitis B immunoglobulin (HBIg) and oral antiviral medication. In the first 6 months after liver transplantation, patients receive treatment with intravenous HBIg to maintain blood antihepatitis B (antiHBs)antibody concentrations above 100 IU/L, the level considered safe for preventing hepatitis B reinfection.

Zutectra is an HBIg preparation for subcutaneous injection that is approved in the EU for the 'prevention of HBV reinfection in HBV DNA negative patients ≥ 6 months after liver transplantation for hepatitis B induced liver failure'. The purpose of this study is to show that earlier subcutaneous HBIg treatment with Zutectra after liver transplantation can prevent hepatitis B reinfection.

Treatment with subcutaneous HBIg (Zutectra) at home is manageable for the majority of patients and is more convenient for patients compared to intravenous treatment that must take place in the hospital setting.

Fourty patients will take part in the study at approximately 19 centres in UK, France, Italy and Spain. Patients who are eligible for the study will receive treatment with Zutectra for 24 weeks.

During the study, the safety and effectiveness of Zutectra will be assessed by checking for symptoms of hepatitis B related infection, as well as monitoring blood levels of antiHBs antibodies and hepatitis B surface antigen (HBsAg).

lead_sponsor: Biotest

sponsor_collaborators:
Biotest
AMS Advanced Medical Services GmbH

location_country:
Italy
United Kingdom
Spain
France

location_facility: Hospital General Universitario Gregorio Maranon

location_facility: Azienda ospedaliera "G. Brutzu" di Cagliari

location_facility: Azienda Ospedaliera Ospedale Niguarda Ca Granda-Chirurgia

location_facility: Fondazione Policlinico Tor-Vergata U.O.C.

location_facility: Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari

location_facility: Liver and Multivisceral Transplant Center, University of Modena and Reggio Emilia

location_facility: University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital

location_facility: Azienda Ospedialera Universitaria di Padova

lead_sponsor_type: industriel


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

acronym: PASSION

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

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

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

status: Active, not recruiting

time_perspective: Cross-Sectional

ipd_sharing: Yes

lead_sponsor: Assistance Publique - Hôpitaux de Paris

sponsor_collaborators:
Assistance Publique - Hôpitaux de Paris
MSD France

intervention_type: Behavioral


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

acronym: PARCOURS

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

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

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

status: Unknown status

lead_sponsor: University Hospital, Caen

sponsor_collaborators:
University Hospital, Caen
MSD France

status_simplified: Unknown


title: Evaluation of 11 C-Choline PET-CT for Detection of Hepatocellular Carcinoma

acronym: CHOLPET

summary:
Hepatocellular carcinoma (HCC)is the most frequent primitive tumour of the liver.

Recently, several research studies reported that 11C-choline PET has shown a high detection rate of well differentiated HCC, which is an early stage of primary liver cancer. The aim of this study was to prospectively evaluate the diagnostic accuracy of 11C-choline PET-CT to detect HCC in cirrhotic or non cirrhotic patients.

design_allocation: Non-Randomized

ReferenceType: background

ReferenceCitation: Talbot JN, Fartoux L, Balogova S, Nataf V, Kerrou K, Gutman F, Huchet V, Ancel D, Grange JD, Rosmorduc O. Detection of hepatocellular carcinoma with PET/CT: a prospective comparison of 18F-fluorocholine and 18F-FDG in patients with cirrhosis or chronic liver disease. J Nucl Med. 2010 Nov;51(11):1699-706. doi: 10.2967/jnumed.110.075507. Epub 2010 Oct 18.

ReferenceCitation: Tolvanen T, Yli-Kerttula T, Ujula T, Autio A, Lehikoinen P, Minn H, Roivainen A. Biodistribution and radiation dosimetry of [(11)C]choline: a comparison between rat and human data. Eur J Nucl Med Mol Imaging. 2010 May;37(5):874-83. doi: 10.1007/s00259-009-1346-z. Epub 2010 Jan 13.

ReferenceCitation: Park JW, Kim JH, Kim SK, Kang KW, Park KW, Choi JI, Lee WJ, Kim CM, Nam BH. A prospective evaluation of 18F-FDG and 11C-acetate PET/CT for detection of primary and metastatic hepatocellular carcinoma. J Nucl Med. 2008 Dec;49(12):1912-21. doi: 10.2967/jnumed.108.055087. Epub 2008 Nov 7.

ReferenceCitation: Ho CL, Yu SC, Yeung DW. 11C-acetate PET imaging in hepatocellular carcinoma and other liver masses. J Nucl Med. 2003 Feb;44(2):213-21.

ReferenceCitation: Hwang KH, Choi DJ, Lee SY, Lee MK, Choe W. Evaluation of patients with hepatocellular carcinomas using [(11)C]acetate and [(18)F]FDG PET/CT: A preliminary study. Appl Radiat Isot. 2009 Jul-Aug;67(7-8):1195-8. doi: 10.1016/j.apradiso.2009.02.011. Epub 2009 Feb 20.

ReferenceCitation: Talbot JN, Gutman F, Fartoux L, Grange JD, Ganne N, Kerrou K, Grahek D, Montravers F, Poupon R, Rosmorduc O. PET/CT in patients with hepatocellular carcinoma using [(18)F]fluorocholine: preliminary comparison with [(18)F]FDG PET/CT. Eur J Nucl Med Mol Imaging. 2006 Nov;33(11):1285-9. doi: 10.1007/s00259-006-0164-9. Epub 2006 Jun 27.

ReferenceCitation: Yamamoto Y, Nishiyama Y, Kameyama R, Okano K, Kashiwagi H, Deguchi A, Kaji M, Ohkawa M. Detection of hepatocellular carcinoma using 11C-choline PET: comparison with 18F-FDG PET. J Nucl Med. 2008 Aug;49(8):1245-8. doi: 10.2967/jnumed.108.052639. Epub 2008 Jul 16.

ReferenceCitation: Salem N, Kuang Y, Wang F, Maclennan GT, Lee Z. PET imaging of hepatocellular carcinoma with 2-deoxy-2[18F]fluoro-D-glucose, 6-deoxy-6[18F] fluoro-D-glucose, [1-11C]-acetate and [N-methyl-11C]-choline. Q J Nucl Med Mol Imaging. 2009 Apr;53(2):144-56. Epub 2008 Nov 28.

ReferenceCitation: Hara T, Kosaka N, Shinoura N, Kondo T. PET imaging of brain tumor with [methyl-11C]choline. J Nucl Med. 1997 Jun;38(6):842-7.

ReferenceCitation: Hara T, Kosaka N, Kishi H. PET imaging of prostate cancer using carbon-11-choline. J Nucl Med. 1998 Jun;39(6):990-5.

ReferenceCitation: Li CW, Kuo YC, Chen CY, Kuo YT, Chiu YY, She FO, Liu GC. Quantification of choline compounds in human hepatic tumors by proton MR spectroscopy at 3 T. Magn Reson Med. 2005 Apr;53(4):770-6. doi: 10.1002/mrm.20412.

ReferenceCitation: Kojiro M, Roskams T. Early hepatocellular carcinoma and dysplastic nodules. Semin Liver Dis. 2005;25(2):133-42. doi: 10.1055/s-2005-871193.

ReferenceCitation: Kim HO, Kim JS, Shin YM, Ryu JS, Lee YS, Lee SG. Evaluation of metabolic characteristics and viability of lipiodolized hepatocellular carcinomas using 18F-FDG PET/CT. J Nucl Med. 2010 Dec;51(12):1849-56. doi: 10.2967/jnumed.110.079244.

ReferenceCitation: Kim YK, Lee KW, Cho SY, Han SS, Kim SH, Kim SK, Park SJ. Usefulness 18F-FDG positron emission tomography/computed tomography for detecting recurrence of hepatocellular carcinoma in posttransplant patients. Liver Transpl. 2010 Jun;16(6):767-72. doi: 10.1002/lt.22069.

ReferenceCitation: Wolfort RM, Papillion PW, Turnage RH, Lillien DL, Ramaswamy MR, Zibari GB. Role of FDG-PET in the evaluation and staging of hepatocellular carcinoma with comparison of tumor size, AFP level, and histologic grade. Int Surg. 2010 Jan-Mar;95(1):67-75.

ReferenceCitation: Khan MA, Combs CS, Brunt EM, Lowe VJ, Wolverson MK, Solomon H, Collins BT, Di Bisceglie AM. Positron emission tomography scanning in the evaluation of hepatocellular carcinoma. J Hepatol. 2000 May;32(5):792-7. doi: 10.1016/s0168-8278(00)80248-2.

ReferenceCitation: Delbeke D, Martin WH, Sandler MP, Chapman WC, Wright JK Jr, Pinson CW. Evaluation of benign vs malignant hepatic lesions with positron emission tomography. Arch Surg. 1998 May;133(5):510-5; discussion 515-6. doi: 10.1001/archsurg.133.5.510.

ReferenceCitation: Okazumi S, Isono K, Enomoto K, Kikuchi T, Ozaki M, Yamamoto H, Hayashi H, Asano T, Ryu M. Evaluation of liver tumors using fluorine-18-fluorodeoxyglucose PET: characterization of tumor and assessment of effect of treatment. J Nucl Med. 1992 Mar;33(3):333-9.

ReferenceCitation: Bruix J, Sherman M; Practice Guidelines Committee, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma. Hepatology. 2005 Nov;42(5):1208-36. doi: 10.1002/hep.20933. No abstract available.

ReferenceCitation: Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, Christensen E, Pagliaro L, Colombo M, Rodes J; EASL Panel of Experts on HCC. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol. 2001 Sep;35(3):421-30. doi: 10.1016/s0168-8278(01)00130-1. No abstract available.

lead_sponsor: Commissariat A L'energie Atomique

sponsor_collaborators:
Commissariat A L'energie Atomique
Assistance Publique - Hôpitaux de Paris


title: Primary-Pneumocystis Infection: Pneumocystis Jirovecii Detection in Nasopharyngeal Aspirates From Symptomatic Infants

acronym: CAPRI-PC

summary: To determine the prevalence of P. jirovecii in nasopharyngeal aspirations of neonates and infants hospitalized for symptomatic respiratory infection.

lead_sponsor: University Hospital, Brest


title: European Registry of Patients With Infantile-onset Spinal Muscular Atrophy

summary: IO-SMA-Registry is a prospective, longitudinal and observational study which objective is to collect prospectively information on longevity, psychomotor development and respiratory function of patients with infantile-onset spinal muscular atrophy.

ipd_sharing: Undecided

lead_sponsor: Institut de Myologie, France

location_facility: Unité de neurologie pédiatrique - Hôpital des enfants

location_facility: Service de Rééducation Pédiatrique Infantile " L'Escale " - Hôpital Femme Mère Enfant

location_facility: Maladie Neuromusculaire de l'enfant - Service Maladies infectieuses et neurologie infantile - Hôpital Roger Salengro


acronym: AJIBIOREM

summary: As biologic treatments are expensive and associated with some concerns regarding long-term safety, investigator hypothesize that early tapering and then withdrawal of biological agent, in an homogenous group of children with juvenile idiopathic arthritis achieving inactive disease, is safe and not inferior to the maintenance of stable treatment intensity over 24 weeks. In addition, investigator also hypothesize that an earlier tapering of treatment is associated with a better quality-of-life and a general cost saving effect. MRP8/14 will be studied as a potential biomarker for the risk of relapse. A study for biologic agent, anti-biologic agent antibodies and a pharmacogenomic approach will complete the research, as pharmacokinetic study during withdrawal of biologic treatment are rare in children.

title: Treatment Tapering in Oligoarticular or Rheumatoid Factor Negative Polyarticular Juvenile Idiopathic Arthritis With Inactive Disease on Biologic Therapy

primary_purpose: Treatment

source: euctr

appel_a_projets: PHRCN

region: Île-de-France

nom_etablissement: ASSISTANCE PUBLIQUE-HOPITAUX DE PARIS

type_etablissement: CHUR

acronyme: AJIBIOREM

titre: Décroissance thérapeutique dans l'arthrite juvénile idiopathique oligoarticulaire ou polyarticulaire sans facteur rhumatoïde en maladie inactive sous biothérapie

discipline_principale: rhumatologie

nom_porteur: QUARTIER DIT MAIRE

prenom_porteur: Pierre


title: A Multicenter Randomized Phase II Study Evaluating Tolerance and Efficacy of Capecitabine 5/7 Days With Weekly Paclitaxel Versus the Recommended Treatment Plan of Weekly Paclitaxel-capecitabine, in Patients With Metastatic Breast Cancer.

summary: Tolerance and efficacy of administration of capecitabine 5 out of 7 days associated with weekly paclitaxel compared to the recommended treatment plan of weekly paclitaxel - capecitabine, in patients with metastatic breast cancer.

lead_sponsor: ARCAGY/ GINECO GROUP


title: Phase II, Multicenter, Open Label, Prospective to Evaluate Efficacy and Tolerance of a Chemoimmunotherapy With HyperCVAD or Vincristine/Dexamethasone Plus the Anti-CD22 Monovlonal Antobody Epratuzumab for the Treatment of Adult Relapsed/Refractory CD22+ B-Acute Lymphoblastic Leukaemia Patients : CHEPRALL Study, a GRAALL Study.

acronym: CHEPRALL

summary:
Patients with relapsed/refractory adult acute lymphoblastic leukemia (ALL)have a very dismal prognosis. In this case, allogeneic transplantation is the only curative treatment when patient have obtained a second complete remission (CR. In France, in patients younger than 60 years old,the HyperCVAD regimen used by the MDAnderson in Houston is generally applied. In older patients (>=60 years)or young patients <= 60 years no eligible for intense chemotherapy, a combination of vincristine + Dexamethasone is generally chosen in order to avoid too much toxicity but the result is worse in term of CR.

More than 90% of ALL with a B phenotype (2/3 of cases in adults)express the surface antigen CD22 on leukemic blasts which thus represents an interesting target for therapy. Epratuzumab is a humanized anti-CD22 antibody produced by Immunomedics, Inc, Morris Plain (New Jersey, USA). Epratuzumab has already shown efficacy in lymphoma patients. Only one study, including 15 children, has been published so far reporting the efficacy and the toxicity of Epratuzumab in the setting of ALL in monotherapy, one can observe 8 stable disease, 3 progressions and 4 partial responses. When combining chemotherapy and Epratuzumab, 9CR were observed with acceptable toxicity. Tolerance was acceptable.

The French GRAALL group proposes to test an age-adapted combination of chemotherapy + Epratuzumab, in refractory/relapses CD22+ B ALL patients in order to improve their prognosis, in term of CR, survival and of number of patients eligible for allograft.

lead_sponsor: Nantes University Hospital

location_facility:
Haut-Leveque Hospital
St Antoine
Institut Paoli Calmette
Edouard Herriot Hospital
Nantes University Hospital
CHU de Poitiers
Saint Louis Hospital
Angers University Hospital
HEnri Mondor Hospital
Purpan Hospital
University Hospital


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

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

lead_sponsor: LEO Pharma

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


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

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

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


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

acronym: COELIOCHIP

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

lead_sponsor: Hospices Civils de Lyon

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


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

acronym: BIG-RENAPE

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

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

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

primary_purpose: Health Services Research

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

publisher_dissemination: Wolters Kluwer Health

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

oa_colors: green other

oa_host_type: publisher;repository

evidence: open (via crossref license, author manuscript)

host_type: publisher

license: publisher-specific-oa

license_normalized: publisher-specific

version: acceptedVersion

evidence: oa repository (via OAI-PMH doi match)

host_type: repository

license: cc-by-nc

license_normalized: cc-by-nc

repository_institution: Le Centre pour la Communication Scientifique Directe - HAL - Université Paris Descartes

repository_normalized: HAL

version: publishedVersion

repository_institution: Le Centre pour la Communication Scientifique Directe - HAL - ParisTech

repositories_concat: HAL

unpaywall_oa_status: hybrid


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

acronym: CTR

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

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

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

oa_host_type: repository

license_normalized: no license

repository_institution: PubMed Central - Europe PMC

repository_normalized: PubMed Central

evidence: oa repository (via pmcid lookup)

repositories_concat: PubMed Central

unpaywall_oa_status: green

publisher_dissemination: Mary Ann Liebert Inc

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

lead_sponsor: Jaeb Center for Health Research

location_country:
United States
Israel
Italy
France

location_facility: Schneider Children's Medical Center of Israel

location_facility: University of Colorado Health Sciences Center- Barbara Davis

intervention_type: Device


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

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

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

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

lead_sponsor: Decathlon SE

sponsor_collaborators:
Decathlon SE
EFOR, France

location_facility: Centre de rééducation et de balnéothérapie Kinés Faches


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

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

status: Terminated

location_facility: Centre Hospitalier Universitaire de Lille


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

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

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

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


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

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

ReferenceCitation: Spigelman AD, Williams CB, Talbot IC, Domizio P, Phillips RK. Upper gastrointestinal cancer in patients with familial adenomatous polyposis. Lancet. 1989 Sep 30;2(8666):783-5. doi: 10.1016/s0140-6736(89)90840-4.

ReferenceCitation: Nugent KP, Farmer KC, Spigelman AD, Williams CB, Phillips RK. Randomized controlled trial of the effect of sulindac on duodenal and rectal polyposis and cell proliferation in patients with familial adenomatous polyposis. Br J Surg. 1993 Dec;80(12):1618-9. doi: 10.1002/bjs.1800801244.

ReferenceCitation: Jarvinen HJ, Nyberg M, Peltokallio P. Biliary involvement in familial adenomatosis coli. Dis Colon Rectum. 1983 Aug;26(8):525-8. doi: 10.1007/BF02563746.

ReferenceCitation: Spigelman AD, Owen RW, Hill MJ, Phillips RK. Biliary bile acid profiles in familial adenomatous polyposis. Br J Surg. 1991 Mar;78(3):321-5. doi: 10.1002/bjs.1800780318.

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

ReferenceCitation: Hill MJ, Drasar BS, Williams RE, Meade TW, Cox AG, Simpson JE, Morson BC. Faecal bile-acids and clostridia in patients with cancer of the large bowel. Lancet. 1975 Mar 8;1(7906):535-9. doi: 10.1016/s0140-6736(75)91556-1.

ReferenceCitation: Tanida N, Hikasa Y, Shimoyama T, Setchell KD. Comparison of faecal bile acid profiles between patients with adenomatous polyps of the large bowel and healthy subjects in Japan. Gut. 1984 Aug;25(8):824-32. doi: 10.1136/gut.25.8.824.

ReferenceCitation: van der Werf SD, Nagengast FM, van Berge Henegouwen GP, Huijbregts AW, van Tongeren JH. Colonic absorption of secondary bile-acids in patients with adenomatous polyps and in matched controls. Lancet. 1982 Apr 3;1(8275):759-62. doi: 10.1016/s0140-6736(82)91810-4. No abstract available.

ReferenceCitation: Wilpart M, Mainguet P, Maskens A, Roberfroid M. Structure-activity relationship amongst biliary acids showing comutagenic activity towards 1,2-dimethylhydrazine. Carcinogenesis. 1983 Oct;4(10):1239-41. doi: 10.1093/carcin/4.10.1239.

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

ReferenceCitation: Serfaty L, De Leusse A, Rosmorduc O, Desaint B, Flejou JF, Chazouilleres O, Poupon RE, Poupon R. Ursodeoxycholic acid therapy and the risk of colorectal adenoma in patients with primary biliary cirrhosis: an observational study. Hepatology. 2003 Jul;38(1):203-9. doi: 10.1053/jhep.2003.50311.

ReferenceCitation: Parc Y, Piquard A, Dozois RR, Parc R, Tiret E. Long-term outcome of familial adenomatous polyposis patients after restorative coloproctectomy. Ann Surg. 2004 Mar;239(3):378-82. doi: 10.1097/01.sla.0000114216.90947.f6.

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

sponsor_collaborators:
Assistance Publique - Hôpitaux de Paris
Axcan Pharma


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

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

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

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

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

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

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

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

repository_institution: Le Centre pour la Communication Scientifique Directe - HAL - Diderot

repository_institution: Le Centre pour la Communication Scientifique Directe - HAL - Université de Limoges

repositories_institution: Le Centre pour la Communication Scientifique Directe - HAL - Université Paris Descartes

location_facility: Nouvel Hopital Civil - CHU de Strasbourg

location_facility: Groupe Hospitalier Pellegrin - CHU de Bordeaux

location_facility: CLIMAL (Centre Libéral Imagerie Médicale Agglomération Lille)

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

intervention_type: Procedure


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

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

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

sponsor_collaborators:
Assistance Publique - Hôpitaux de Paris
Agence de La Biomédecine
Fondation de France

location_facility: APHP - Lariboisière hospital - réanimation chirurgicale


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

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

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


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

acronym: VITADOS

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

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

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

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

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


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

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

lead_sponsor: Amicus Therapeutics France SAS

location_facility: CHU de Grenoble site Nord, Hôpital Albert Michallon


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

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

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

location_facility: Groupe hospitalier Diaconesses Croix Saint-Simon


title: Echocardiography and PEA Measurements in CRT Therapy

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

lead_sponsor: LivaNova

location_facility:
CHU Rennes
Clinique Bizet
Nouvelles Cliniques Nantaises
CHU Pontchaillou


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

acronym: LPP

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

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

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

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

lead_sponsor: Centre Hospitalier Universitaire, Amiens

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


title: Pilot Study for the Experimental Validation of the Intrinsic Diagnostic Performance Among the First Dod Team for the Canine Olfactory Detection of COVID-19 on Sweat Samples From Persons Tested by PCR SARS-CoV-2.

acronym: CYNOCOV

summary:
Considering the favorable preliminary data of few european diagnostic studies on dog detection, we develop in 2021 a pilot study in response to the plan of CHU Bordeaux and Nouvelle Aquitaine French region for an expanded, reliable and alternative rapid dog olfactory detection of COVID during pandemic period.

Our hypothesis is that validated olfactory detection on sweat or face mask collection by dogs would increase the acceptability and propensity to be tested in different population groups, given the non-invasive nature of sweat and face mask; compared to the unpleasant aspect of nasal swabs for PCR or rapid antigenic tests.

To reach this objective, we recruited a dog team to be trained and assessed (all-volunteers masters and dogs) and we will recruit participants with positive and negative PCR test. The diagnostic performance of canine olfactory detection of COVID-19 on sweat and face collection will be compared to the nasal SARS-Cov-2 PCR test of the participants.

lead_sponsor: University Hospital, Bordeaux

location_facility:
Hospital Périgueux
Hospital Libourne
University Hospital Limoges, France
Hospital Dax
Universtity Hospital Poitiers
University Hospital Bordeaux, France


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

acronym: VIRUS

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

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

time_perspective: Retrospective

sponsor_collaborators:
Nantes University Hospital
WINFOCUS-France


title: Use of Selincro and Impact on Usual Practice

acronym: USE-PACT

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

lead_sponsor: University of Bordeaux

sponsor_collaborators:
University of Bordeaux
Lundbeck France


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

acronym: PCD

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

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

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

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

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

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

This study will contain 3 treatment phases:

Study treatment phase:

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

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

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

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

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

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

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

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

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

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

oa_host_type: publisher

evidence: open (via free article)

unpaywall_oa_status: bronze

publisher_dissemination: American Society of Hematology

lead_sponsor: Institut Curie

sponsor_collaborators:
Institut Curie
Intergroupe Francophone du Myelome
Celgene Corporation

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

location_facility: Centre Hospitalier départemental de Vendée

location_facility: Institut d'Hématologie de Basse Normandie - IHBN


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

acronym: ECOST-CRT

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

lead_sponsor: University Hospital, Lille

sponsor_collaborators:
University Hospital, Lille
Biotronik France


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

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

time_perspective: Other

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

evidence: open (via crossref license)

lead_sponsor: Medical University of Vienna

collaborators: Vascular Surgical Research Group, Imperial College, London, UK

collaborators: Sanger Heart and Vascular Institute, Charlotte, NC

collaborators: Loyola University Medical Center, Maywood, IL

collaborators: Heidelberg University Hospital, Heidelberg, Germany

collaborators: University Hospital of Freiburg, Freiburg, Germany

collaborators: University Hospital of Mainz, Mainz, Germany

collaborators: Diakonie Hospital Jung-Stilling, Siegen, Germany

collaborators: Sentara Vascular/Eastern Virginia Medical School, Norfolk, VA

collaborators: Maastricht University Medical Centre, Maastricht, Netherlands

collaborators: I.R.C.C.S. Policlinico San Donato, San Donato Milanese, Italy

collaborators: Memorial Care Long Beach Heart & Vascular Institute, Long Beach, CA

location_country: Germany France

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

location_facility: Marie Lannelongue Hospital (Paris, France)


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

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

ReferenceType: result

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

lead_sponsor: Assistance Publique - Hôpitaux de Paris

location_facility: Clinical Investigation Center, European George Pompidou Hospital


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

acronym: CIMI

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

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

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

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

lead_sponsor: University Hospital, Clermont-Ferrand


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

acronym: PHARMAID

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

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

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

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

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

appel_a_projets: PREPS

region: Auvergne-Rhône-Alpes

nom_etablissement: HOSPICES CIVILS DE LYON

acronyme: PHARMAID

titre: Evaluation de l'impact d'un suivi PHARMaceutique intégré à un accompagnement psychosocial sur le fardeau des AIDants naturels de patients âgés atteints de maladie d'Alzheimer et maladies apparentées

discipline_principale: organisation des soins

nom_porteur: MOUCHOUX

prenom_porteur: Christelle


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

acronym: SCLEROGLIVEC

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

collaborators:
Ministry of Health, France
Novartis

sponsor_collaborators:
University Hospital, Bordeaux
Ministry of Health, France
Novartis

location_facility: Service de Médecin interne - Hôpital central

location_facility: Service de dermatologie - CHU de Limoges

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

location_facility: Néphrologie et Médecine interne - CH de Valenciennes

location_facility: Service de Médecine interne - Hôpital Saint Louis

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

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

location_facility: Service de Rhumatologie - CHU de Strasbourg

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

location_facility: Service de Médecine interne - CHU de Tours


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

acronym: GENPHENACL

summary:
The main objectives of this study are:

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

Edit important recommendations for:

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


title: Aging,Sleep and Cognitive Process

acronym: SOMVIE

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

primary_purpose: Basic Science

location_facility:
Medes-Imps
Uh Purpan
Genpphass


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

acronym: Elasto-ICU

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

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

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

oa_colors: green gold

evidence: oa journal (via doaj)

license: cc-by

license_normalized: cc-by

repository_institution: Le Centre pour la Communication Scientifique Directe - HAL - Inria

repository_institution: Le Centre pour la Communication Scientifique Directe - HAL - CEA - Commissariat à l’énergie atomique

repositories:
HAL
PubMed Central

repositories_concat: HAL;PubMed Central

unpaywall_oa_status: gold

publisher_dissemination: Springer-Nature


title: Psychophysiological Study of Pain Perception in Depressed Patients With Suicidal Risk

summary:
Joiner's interpersonal theory of suicide postulates that the wish of death comes from feelings of perceived burdensomeness and thwarted belongingness. But, only people who have acquired the capability to kill themselves will attempt suicide. The acquired capability refers to a reduction of fear to death, and a higher pain tolerance. Indeed, to commit suicide involves to endure pain during the act. Thus, higher pain tolerance seems to be a necessary feature for suicidal act.

Past studies have shown higher pain threshold and tolerance in suicidal patients, whatever the stimulus was (electric, thermic or mechanical), compared to patients without suicide history. Moreover, Caceda and colleagues demonstrated higher pain threshold in recent suicide attempters (suicidal act within 72h) compared with depressed patients. Five days after the initial evaluation, pain threshold of recent suicide attempters decreased to be similar to depressed patients with suicidal ideation. Therefore, it may exist a specific state during which the pain tolerance is increased. During this "hypoalgesic state" patients with suicidal ideation could attempt suicide to get relief from suffering.

However, little is known about the specific mechanisms that are responsible for the higher pain threshold and tolerance in suicide attempters. Pain is a dynamic system that results from excitatory and inhibitory messages. The modification of one of these mechanisms could explain the higher tolerance in recent suicide attempters. Three of them are of particular interest:

The conditioned pain modulation (CPM) is a modulatory pain mechanism. CPM works through descending pathway that reaches the spinal cord and modulates pain processing from the first nociceptive synapse.In recent suicidal patients, an increase of the CPM could explain higher pain tolerance.
The "wind-up" mechanism is defined as the highest excitability of the second order nerve. Even if the stimulus remains stable, pain continuously raises. In recent suicide attempters, a reduction of this mechanism could explain higher pain tolerance.
The threshold of Aδ and C nociceptors. If a nociceptive fiber is less excitable than the other, it would explain higher pain threshold.

lead_sponsor: University Hospital, Montpellier

sponsor_collaborators:
University Hospital, Montpellier
Clinea psychiatrie France

location_facility:
University Hospital of Montpellier
Clinic La Lironde

intervention_type: Biological


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

acronym: PONATINIB-AML

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

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

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

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

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

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

lead_sponsor: Versailles Hospital

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


acronym:
DURIGAST

 DURIGAST

lead_sponsor: Federation Francophone de Cancerologie Digestive

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

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

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

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

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

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

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


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

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

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

lead_sponsor: Unither Pharmaceuticals, France

sponsor_collaborators:
Unither Pharmaceuticals, France
AIXIAL Development

location_country: Italy Poland Spain France

location_facility: Hospital Odontológico Universitat Barcelona

location_facility: Oral Surgery Department, Central Clinical Hospital

location_facility: Oral surgery Medical University of Lublin

location_facility: Centro Médico Teknon - Grupo Quironsalud

location_facility: Hospitalario Universitario de Santiago (CHUS)

location_facility: Faculty of Medicine of the UNIVERSITY OF MURCIA

location_facility: NZOZ Akademicka Poliklinika Stomatologiczna

location_facility: Department of maxilla facial Surgery -University of Udine

location_facility: Facultad de Odontología de la Universidad de Granada


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

acronym: pGLILD

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

ReferenceCitation: Bates CA, Ellison MC, Lynch DA, Cool CD, Brown KK, Routes JM. Granulomatous-lymphocytic lung disease shortens survival in common variable immunodeficiency. J Allergy Clin Immunol. 2004 Aug;114(2):415-21. doi: 10.1016/j.jaci.2004.05.057.

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

lead_sponsor: Central Hospital, Nancy, France

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


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

acronym: CORISAT

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

Secondary purposes are:

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

location_facility: Service ORL - Institut Louis Mathieu - CHRU NANCY


title: A Dose-Escalation Open-Label Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of CEP-9722 (a PARP 1 and PARP 2 Inhibitor) in Combination With Gemcitabine and Cisplatin in Patients With Advanced Solid Tumors or Mantle Cell Lymphoma

summary: The primary objective of the study is to determine the maximum tolerated dose (MTD) of CEP-9722 in combination with gemcitabine and cisplatin in patients with advanced solid tumors or mantle cell lymphoma.

lead_sponsor: Cephalon

location_country: Belgium France

location_facility:
Teva Investigational Site 1
Teva Investigational Site 2
Teva Investigational Site 3