title: Effect of Oleactiv® on LDL Oxidability in Volunteers With Moderate Hypercholesterolemia - a Controlled, Randomized, Double-blind Study

acronym: e-POL

summary:
Oleactiv® have previously demonstrated beneficial effects in an animal model of diet-induced atherosclerosis. After a 12-week supplementation, a substantial reduction of aortic fatty streak area has been observed. Also, Oleactiv®-supplemented hamsters displayed significant decrease of both non-HDL-cholesterol and triglycerides levels. Also, phenolic compounds from Oleactiv® demonstrated that increase of cholesterol efflux capacity (CEC) is one of the mechanisms that may explain preventive effect on atheroma development.

These effects observed in animals will thus be investigated in human. The main hypothesis of the present study is that phenolic compounds from Oleactiv® may improve LDL oxidability in volunteers with moderate hypercholesterolemia after 3 weeks of consumption.

ipd_sharing_description: IPD will available only for sponsor


title: Single-center Retrospective Observational Study of Cotrimoxazole Dosing in Intensive Care Unit

summary: Trimethoprim/sulfamethoxazole (TMP/SMX, cotrimoxazole) is the first-line therapy for Pneumocystis jirovecii pneumonia and bacterial infections in critically ill patients, where acute kidney injury (AKI) and renal replacement therapy (RRT) are regularly observed. Both may change half-life and subsequent concentrations. Specifically, Trimethoprim (TMP) is eliminated renally, whereas sulfamethoxazole (SMX) elimination is 80%metabolic/20%renal. Despite decades of cotrimoxazole use, data in acute kidney injury (AKI) are scarce and no consensus on dosing strategy has been established. Besides, pharmacodynamic parameter has not been determined, leading to an uncertainty on the dosing regimen.

study_start_date_type: Actual

status: Completed

study_completion_date_type: Actual

study_type: Observational

time_perspective: Retrospective

enrollment_type: Actual

ipd_sharing: No

lead_sponsor: Centre Hospitalier Universitaire de Saint Etienne

intervention_type: Other

lead_sponsor_type: academique

status_simplified: Completed


title: Central Venous Oxygen Saturation and Carbone Dioxide (CO2)-Derived Indices in the Critically: Correlation of Measurements According to the Site of Harvest (Femoral Versus Jugular Vein)

summary:
The optimal management of shock states requires a precise evaluation of several parameters, clinical, biological, hemodynamic, and echocardiographic. Among these, parameters that measure O2 and CO2 consumption are of a great interest, especially PCO2 arteriovenous gradient (PCO2 gap) and O2 arteriovenous difference [D(a-v) O2]. The PCO2 gap best correlates with cardiac output while the PCO2gap/D(a-v)O2 ratio would be earlier and more specific than blood lactate assay in assessing tissue hypoperfusion secondary to shock.

The PCO2 gap and the PCO2gap/D (a-v) O2 ratio have been evaluated from gas measurements of venous blood collected from the pulmonary artery and from the superior vena cava area. However, in some patients the placement of a catheter in the superior vena cava is difficult or even impossible due to thrombosis, vascular occlusions and other reasons… In these cases, the inferior vena cava is used for drugs infusion, nutrition and possibly samples. Gasometric samples in lower cellar territory have not yet been validated and may not be correlated with measurements in upper cellar territory. It is therefore useful for current practice to validate samples in lower cellar territory and demonstrate their correlation with measurements made in upper cellar territory.

During an observation period, in patients with catheters in the superior and inferior vena cava for therapeutic indications (renal replacement therapy,...), the investigators systematically took gas measurements at the femoral and jugular sites. the investigators used these data to assess the correlation of PCO2 gap measurements and carbon dioxide-derived indices according to the harvest site : jugular and femoral venous.

time_perspective: Prospective

ipd_sharing: Undecided

ipd_sharing_description: NC

lead_sponsor: University Hospital, Montpellier


title: Exploring the Relationship Between the Gut Microbiome Based Metagenomic Signature, Physical Fitness Levels and Metabolic Responses to Exercise: a Pilot Study on 50 Healthy Male Volunteers

acronym: EXOMIC

summary: Gut microbiota are all microorganisms including bacteria and microscopic eukaryotes that live in the digestive tracts of humans or mammals. During the last decade, some authors highlighted that a link exists between gut microbiota and sport performance. In this project, we hypothesize that gut microbiota is able to adapt to the energy needs of the body, really higher in top-level athletes or considerably lower in inactive individuals. In this context, this clinical study aims to characterize the bacterial metagenome of gut microbiota from populations located in a continuum from sedentary people to top-level athletes with high (i.e. soccer players), even very high energy needs (i.e. cyclists). The finality of this project is thus to determine if it exists some bacterial profile allowing to characterize, even to predict, the energy metabolism of an athlete and so the probability to be performant in competition.

status: Recruiting

study_completion_date_type: Anticipated

time_perspective: Cross-Sectional

enrollment_type: Anticipated

ReferenceType: background

ReferenceCitation: Nay K, Jollet M, Goustard B, Baati N, Vernus B, Pontones M, Lefeuvre-Orfila L, Bendavid C, Rué O, Mariadassou M, Bonnieu A, Ollendorff V, Lepage P, Derbré F, Koechlin-Ramonatxo C. Gut bacteria are critical for optimal muscle function: a potential link with glucose homeostasis. Am J Physiol Endocrinol Metab. 2019 Jul 1;317(1):E158-E171. doi: 10.1152/ajpendo.00521.2018. Epub 2019 Apr 30.

ReferenceCitation: Clarke SF, Murphy EF, O'Sullivan O, Lucey AJ, Humphreys M, Hogan A, Hayes P, O'Reilly M, Jeffery IB, Wood-Martin R, Kerins DM, Quigley E, Ross RP, O'Toole PW, Molloy MG, Falvey E, Shanahan F, Cotter PD. Exercise and associated dietary extremes impact on gut microbial diversity. Gut. 2014 Dec;63(12):1913-20. doi: 10.1136/gutjnl-2013-306541. Epub 2014 Jun 9.

ReferenceCitation: Barton W, Penney NC, Cronin O, Garcia-Perez I, Molloy MG, Holmes E, Shanahan F, Cotter PD, O'Sullivan O. The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level. Gut. 2018 Apr;67(4):625-633. doi: 10.1136/gutjnl-2016-313627. Epub 2017 Mar 30.

ReferenceCitation: Voorhies AA, Mark Ott C, Mehta S, Pierson DL, Crucian BE, Feiveson A, Oubre CM, Torralba M, Moncera K, Zhang Y, Zurek E, Lorenzi HA. Study of the impact of long-duration space missions at the International Space Station on the astronaut microbiome. Sci Rep. 2019 Jul 9;9(1):9911. doi: 10.1038/s41598-019-46303-8.

ReferenceCitation: Allen JM, Mailing LJ, Niemiro GM, Moore R, Cook MD, White BA, Holscher HD, Woods JA. Exercise Alters Gut Microbiota Composition and Function in Lean and Obese Humans. Med Sci Sports Exerc. 2018 Apr;50(4):747-757. doi: 10.1249/MSS.0000000000001495.

lead_sponsor: University of Rennes 2

location_facility: University Rennes 2 - Laboratory "Movement, Sport and health Sciences"

intervention_type: Diagnostic Test

status_simplified: Ongoing


title: Impact of an SMS Reminder on Influenza Vaccination Coverage in Patients With Rheumatoid Arthritis Taking Anti-TNF : an Ancillary Study to the French National Registry ART E-cohort

summary:
Biotherapies have significantly improved the prognosis of rheumatoid arthritis (RA), particularly anti-TNF. However, these molecules are associated with a well-demonstrated increase in infectious risk, including an over-risk of pneumococcal and influenza infection.. Therefore, when initiating anti-TNF treatments, it is recommended to update the vaccination schedule of these patients, to vaccinate them against pneumococcus and carry out an annual anti influenza vaccination.. However, vaccination coverage remains sub-optimal. The means to improve this vaccination coverage are multiple but often require human resources. Medical teams often lack time, nursing interventions are effective but again requires the availability of the health care team. The use of modern digital means (automatic reminders) is an attractive alternative to increase immunization coverage without the use of medical or paramedical time.

The objective of the study is to evaluate the effectiveness, in terms of immunization coverage, of SMS and/or email reminders reminding the need to vaccinate against seasonal influenza compared to usual care, in patients with RA on biotherapies participating in the e-cohort of the French ART Registry (NCT03062865).

This study will be based on the ART Registry e-cohort. This will be a randomized controlled trial in patients in the ART e-cohort. The patients will be allocated in one of the 2 arms : one arm receiving reminders by email and SMS of the influenza vaccination, the other arm with absence of reminders. This study will be conducted during the annual French National communication campaign to encourage influenza vaccination.

The main evaluation criterion will be the influenza vaccination coverage rate at the end of the vaccination campaign. It will be compared between the two arms.

study_type: Interventional

design_allocation: Randomized

primary_purpose: Prevention

lead_sponsor: Societe Francaise de Rhumatologie

lead_sponsor_type: industriel


title: Selection of Farnesoid X Receptor (FXR) Ligands as Latency Reversal Agents (LRA) of Latent HIV Proviruses in Circulating CD4+ T Lymphocytes Isolated From Patients With Undetectable HIV Viremia Under cART (Combined Antiretroviral Treatments)

summary:
The FXReservoir#1 study (NCT03618862) showed that certain FXR ligands reactivate latent viruses in the reservoir circulating in all HIV+ patients tested. These molecules appear as latency reversal agents (LRA) of silent viruses of the HIV reservoir. They can be part of the strategy to eradicate this reservoir, responsible for recurrences of the infection when combined anti-retroviral treatments are stopped.

Two effective leads have been identified on in vitro tests and on ex vivo reactivation using FXReservoir#1. These molecules come from a chemical library of FXR ligands developed by the Inserm team behind the discovery of a role for FXR in viral infections.

A first series of optimized molecules derived from these leads has been synthesized; these molecules, after screening on viral and ADMET (Absorption, Distribution, Metabolisme, Excretion and Toxicity) in vitro tests, must be tested ex vivo on CD4+ lymphocytes from the circulating peripheral reservoir of HIV+ patients in order to select the best molecules with LRA activity. This step is essential before considering the clinical development of an LRA.

study_start_date_type: Anticipated

status: Not yet recruiting

primary_purpose: Basic Science

lead_sponsor: Hospices Civils de Lyon

location_facility: Service des maladies infectieuses et tropicales Hôpital de la Croix Rousse

intervention_type: Procedure


title: Impact of Hydrocephalus Treatment on Persistent Disorder of Consciousness Following Acute Brain Injury

acronym: HYCO

summary: After acute brain injury or haemorrhagic stroke, hydrocephalus might participate to consciousness disorder. We plan to explore whether ventriculoperitoneal shunt insertion improves consciousness in patients with vegetative or minimally conscious state and hydrocephalus. Patients with acute brain injury, persistent consciousness disorder and hydrocephalus will be shunted with a detailed follow-up at 3 months combining: clinical evaluation, FluoroDésoxyGlucose positron emission tomography imaging, high density electroencephalogram, electrocardiogram Holter and sympathetic activity by microneurography.

lead_sponsor: University Hospital, Toulouse


title: Impact of a Multidisciplinary Protocol of Respiratory Kinesitherapy and Active Music Therapy on Anxiety, Depression and Pain in Lung Transplant Patients: PPKRMA

acronym: PPKRMA

summary:
Transplantation remains the last resort to prolong life when the patient reaches the stage of terminal respiratory failure. Lung transplantation improves survival and quality of life compared to medical treatment, at acceptable costs. However, the burden of the lived reality and the direct consequences of the operation have considerable impact. The transplant patient faces extraordinary physical and psychological challenges.

While quality of life and long-term prognosis are significantly improved, psychopathological disorders are common, mainly anxiety disorders. A high prevalence of psychopathological disorders is reported in most retrospective and prospective studies. These are essentially adjustment disorders, with depressive mood and/or anxiety, reactive to the severity of the pre- and postoperative somatic reality.

The partial or total replacement of the respiratory "bellows" leads to more anxiety disorders than in other transplants. Quality of life is a multidimensional concept that encompasses medical, social, cultural, psychological and economic factors. It is based on four dimensions: physical state, somatic sensations, psychological state, social status. Regarding the quality of psychic evolution after transplantation, among the criteria that are usually analysed we find adaptation to body changes and anxiety management.

Meta-analyses of clinical trials have shown that music therapy, which is based on the use of the properties of music and sound for therapeutic purposes, has an impact on the human being, reducing anxiety, depression and pain. Two clinical trials have shown that pulmonary rehabilitation with active music therapy improves lung function and reduces dyspnoea. The concept of active music therapy, which emphasises sound production and improvisation, is a controlled technique of musical practice for therapeutic purposes. Playing a wind instrument, using vocal techniques and respiratory rhythm modulation techniques, would provide additional benefits for respiratory function.

The use of recorders as an oscillating exhalation resistance device will provide conditions similar to the treatment provided by a flutter, a device that creates exhalation resistance and improves secretion clearance.

Investigators hypothesize that the combination of Respiratory Kinesitherapy and active breath music therapy (PPKRMA) will address anxiety, depression, and pain in lung.

location_facility: Pneumologie C Bât A4 Hôpital cardiologique Louis Pradel, Groupement Hospitalier Est Hospices Civils de Lyon


title: Effectiveness of Partial-body Cryotherapy on the Fatigue of Patients With Multiple Sclerosis During Readaptation Stay

acronym: CRYOSEP

summary: the aim of the study is to evaluate the effectiveness of partial-body cryotherapy (PBC) on the symptoms of patients with multiple sclerosis during a rehabilitation stay.

primary_purpose: Treatment

ReferenceCitation: Pawik M, Kowalska J, Rymaszewska J. The effectiveness of whole-body cryotherapy and physical exercises on the psychological well-being of patients with multiple sclerosis: A comparative analysis. Adv Clin Exp Med. 2019 Nov;28(11):1477-1483. doi: 10.17219/acem/104529.

ReferenceCitation: Bouzigon R, Grappe F, Ravier G, Dugue B. Whole- and partial-body cryostimulation/cryotherapy: Current technologies and practical applications. J Therm Biol. 2016 Oct;61:67-81. doi: 10.1016/j.jtherbio.2016.08.009. Epub 2016 Aug 27. Review.

ReferenceCitation: Radecka A, Knyszyńska A, Łuczak J, Lubkowska A. Adaptive changes in muscle activity after cryotherapy treatment: Potential mechanism for improvement the functional state in patients with multiple sclerosis. NeuroRehabilitation. 2021;48(1):119-131. doi: 10.3233/NRE-201535.

ReferenceCitation: Zielińska-Nowak E, Włodarczyk L, Kostka J, Miller E. New Strategies for Rehabilitation and Pharmacological Treatment of Fatigue Syndrome in Multiple Sclerosis. J Clin Med. 2020 Nov 7;9(11). pii: E3592. doi: 10.3390/jcm9113592. Review.

ReferenceCitation: Miller E, Kostka J, Włodarczyk T, Dugué B. Whole-body cryostimulation (cryotherapy) provides benefits for fatigue and functional status in multiple sclerosis patients. A case-control study. Acta Neurol Scand. 2016 Dec;134(6):420-426. doi: 10.1111/ane.12557. Epub 2016 Jan 18.

lead_sponsor: Fondation Ildys

intervention_type: Device


title: New IMPLANTARY SURGERY Protocol ASSISTED BY PASSIVE ROBOTIQUE: Pilot Study

acronym: NAVIMPLANT

summary: The use of a passive robotic system allows the practitioner to widen the field of indications of flapless surgical access to the implant with an increased operative security and the possibility of an operative modification of the surgical protocol.


title: Language Acquisition in the Brain and Algorithms: Towards Systematic Monitoring of the Evolution of Semantic Representations in Biological and Artificial Neural Networks

acronym: SYNTAXE

summary:
Speech depends on our ability to recursively combine successive words into a complex sense. Although the order of these putative operations (syntax) has been the subject of extensive examination in the way in which the human brain learns to perform a "Semantic composition" remains largely unknown.

The Rothschild Hospital houses a unit specializing in drug-resistant epilepsy in children from 2 to 20 years old.

The identification of the epileptogenic zone often requires making an iEEG recording for a week (implantation of intracerebral electrodes in depth).

Sometimes this recording has to be repeated, providing a unique opportunity to directly record brain activity at different periods of its development.

Children will listen to pre-recorded phrases and stories such as "The Little Prince of Antoine de Saint-Exupéry" while being recorded with iEEG.

time_perspective: Other

lead_sponsor: Fondation Ophtalmologique Adolphe de Rothschild


title: Bypass Versus Endovascular Procedure in Long Lesions of the Superficial Femoral Artery in the Claudicant

acronym: PELI-CAN

summary:
In lower limb peripheral arterial disease, the stage of intermittent claudication has a prevalence of more than 5% over the age of 60, and affects patients who are often still active. Frequent anatomical lesions are strictures / occlusions of the superficial femoral artery.

There is a current low level of evidence for the treatment modalities of long lesions (15-25 cm) of the superficial femoral artery and in particular no clinical trial comparing the femoro-popliteal bypass to the endovascular procedure whose patency in retrospective series. appears lower than that of surgery but nevertheless appears in the European recommendations for first-line treatment, with the absence of a dedicated trial being highlighted.

lead_sponsor: Assistance Publique - Hôpitaux de Paris

location_facility: Assistance Publique Hôpitaux de Paris - CHU Henri Mondor


type: EudraCT Number

title: Pre-exposure Prophylaxis of SARS-CoV-2 Infection (COVID-19) by Monoclonal Antibodies With Early Access Authorization in Immunocompromised Patients. A Prospective Cohort.

acronym: PRECOVIM

summary: This prospective cohort of patients, receiving pre exposure prophylaxis by Anti-SARS-CoV-2 Monoclonal Antibodies, is designed to evaluate the treatment protection against SARS-CoV-2 variants of concerns

lead_sponsor: ANRS, Emerging Infectious Diseases


title: Evaluation of the Effectiveness of a City Hospital Care Network for the Care of Patients With Transient Ischemic Accident (TIA)

acronym: AIT-AMBU-GRE

summary: Transient ischemic accidents (TIA) are a frequent resort to hospitalization in the emergency department and are serious events in terms of recurrence and handicap. The organization of the "TIA sector" at CHUGA aims to facilitate on the one hand the care of the patient during his hospitalization in the emergencies and on the other hand to allow a safer discharge of the patient as well as his follow-up in ambulatory. The aim of this study is to study the feasibility of comprehensive short-term outpatient management after hospitalization in the emergencies. The research hypothesis is that 90% of patients complete all of the 10 recommended examinations for the diagnosis of TIA, analysis of its risk factors and initiation of necessary treatments, if necessary.

ReferenceCitation: Amarenco P, Benavente O. EXPRESS transient ischemic attack study: speed the process! Stroke. 2008 Aug;39(8):2400-1. doi: 10.1161/STROKEAHA.108.514166. Epub 2008 Jul 3. Review.

ReferenceCitation: Amarenco P. Not all patients should be admitted to the hospital for observation after a transient ischemic attack. Stroke. 2012 May;43(5):1448-9. doi: 10.1161/STROKEAHA.111.636753.

ReferenceCitation: Amarenco P, Lavallée PC, Monteiro Tavares L, Labreuche J, Albers GW, Abboud H, Anticoli S, Audebert H, Bornstein NM, Caplan LR, Correia M, Donnan GA, Ferro JM, Gongora-Rivera F, Heide W, Hennerici MG, Kelly PJ, Král M, Lin HF, Molina C, Park JM, Purroy F, Rothwell PM, Segura T, Školoudík D, Steg PG, Touboul PJ, Uchiyama S, Vicaut É, Wang Y, Wong LKS; TIAregistry.org Investigators. Five-Year Risk of Stroke after TIA or Minor Ischemic Stroke. N Engl J Med. 2018 Jun 7;378(23):2182-2190. doi: 10.1056/NEJMoa1802712. Epub 2018 May 16.

ReferenceCitation: Lavallée PC, Meseguer E, Abboud H, Cabrejo L, Olivot JM, Simon O, Mazighi M, Nifle C, Niclot P, Lapergue B, Klein IF, Brochet E, Steg PG, Lesèche G, Labreuche J, Touboul PJ, Amarenco P. A transient ischaemic attack clinic with round-the-clock access (SOS-TIA): feasibility and effects. Lancet Neurol. 2007 Nov;6(11):953-60.

ReferenceCitation: Cucchiara BL, Kasner SE. All patients should be admitted to the hospital after a transient ischemic attack. Stroke. 2012 May;43(5):1446-7. doi: 10.1161/STROKEAHA.111.636746.

lead_sponsor: University Hospital, Grenoble


type: Other Identifier

title: Short-term Pre-OPerative Durvalumab (MEDI 4736) in Early Small Triple Negative Breast Cancer Patients (POP-Durva)

acronym: POP-DURVA

summary:
This study aims to evaluate the efficacy and safety of preoperative Durvalumab in patients with early small (cT1N0) triple negative breast cancer tumors. This preoperative study will recruit patients with early HR-negative breast cancer all invasive types (ER < 1%, PR < 1%, HER2 negative), not candidate for neoadjuvant chemotherapy and eligible for a short-term pre-operative treatment with Durvalumab followed by breast surgery.

A total of 200 patients are planned to be enrolled in the study. Patients will receive IV durvalumab 10mg/kg monotherapy every 2 weeks for a total of 6 weeks, followed by a surgery at Day 42.

status: Suspended

lead_sponsor: Gustave Roussy, Cancer Campus, Grand Paris

intervention_type: Drug

status_simplified: Unknown


title: Impact of Simulation-based Training in Addition to Theoretical Training Versus Theoretical Training Alone for Nurses on the Occurring of Adverse Events Related to Arteriovenous Fistula Puncture in Chronic Hemodialysis Patients.

summary:
Currently, the technique of arteriovenous fistula puncture is transmitted by companionship within hemodialysis units. Although the main principles of the technique are well known and common to all hemodialysis units, strong rationales are still lacking to standardize fine practices such as the relative position of the needles, the angle of attack of the needle at puncture, the position of the bevel at the time of puncture and once the needle is in the vascular lumen.

The training of professionals using a simulation-based training program on the approach to arteriovenous fistula puncture, in a process of optimizing practices and continuous improvement of care, while respecting the principles of andragogy, seems to be a suitable tool. This program is built in a multi-professional team from nephrology, nursing and health simulation.

primary_purpose: Other

lead_sponsor: University Hospital, Caen


title: Optimization of Mother-child Dyad Follow-up by a Multidomain Application: Real-world Cross Sectional Study

summary:
After birth, the mother-child dyad can be impacted by issues which are usually under-detected or detected at early stage. Among these issues, neurodevelopmental disorders (NDD) such as autism spectrum disorder are common and affect 1 in 59 children but are detected after 4 years of age although it could be detected using parent report screens as early as 12 or 18 months of age. Moreover, parents are the main contributors of the screening of NDD in their children. In a recent French survey, the identification of the first symptoms was done by parents in 61% of cases and a health professional in only 14% and the mean age of disease detection was 6.8 years for autism spectrum disorder.

Other troubles that deserve early screening are hearing disorders which are observed in 1 child in 300 at 3 years of age and the main visual trouble in toddlers such as amblyopia which is observed with a prevalence of 3%.

Another issue that deserves improvement is the rate of mandatory or recommended vaccines in toddler which is only 71% for C-meningococcus and 79% for measles or rubella.

Concerning the mother, postnatal depression is defined as an episode of minor or major depression occurring during the first year postpartum with a pooled prevalence of 17.7%. Despite the high prevalence of this disorder and its potential impact on child development it remains underdetected and undertreated in daily practice.

The common point between all these disorders is that they can benefit from early detection by questionnaires intended for parents for their children or for themselves, because early treatment improves prognosis or prevent diseases.

An "all-in-one" multi-domain familial digital health record Patient reported outcomes application has been developing to help for early screening of neurodevelopmental disorders of toddler after birth to 3 years of age and mother's postnatal depression, to improve vaccinations rate of toddlers and to provide advice to parents for child development. The aim of the study is to assess in a real-world data-based the performances of this application.

lead_sponsor: Weprom


title: Diagnostic Performance of a Net Ultrafiltration Challenge to Predict Preload Dependence in Critically Ill Patients Under Continuous Renal Replacement Therapy

acronym: UF CHALLENGE

summary:
Hemodynamic instability episodes are a frequent complication of renal replacement therapies in critically ill patients, and their incidence is associated with worse survival. Hypovolemia, identified by the existence of biventricular preload dependence, is responsible for one episode out of two, and may justify a decrease in or cessation of fluid removal by net ultrafiltration (UF). To date, preload dependence is most frequently identified by evaluating the effects on cardiac output of postural changes (passive leg raising), impact of cardio-pulmonary interactions in ventilated patients, or fluid challenge. However, none of these tests may help identify a patient whose cardiac output is at risk of becoming preload dependent, that is situated at the inflexion point of the Frank Starling curve.

Our study aims to evaluate the effects on cardiac output (measured by a transpulmonary thermodilution technique) of 2 net ultrafiltration challenges, consisting fast removal of 250 ml of ultrafiltrate over 15 and 30 minutes respectively, and compare their diagnostic performance to the reference technique of preload dependence assessed by postural changes (passive leg raising) performed after the UF challenge.

Enrolled participants will undergo both UF challenges, following a randomized crossover design, in which the order of UF challenge duration (15 or 30 minutes) is randomized, separated by a washout period of 24 hours.

primary_purpose: Diagnostic

location_facility: Department of Intensive Care, Croix Rousse hospital, Hospices Civils de Lyon


title: Thrombin Generation Assay to Assess Thrombotic Risk and the Evolution of the Hypercoagulability Profile of Patients With Nephrotic Syndrome

acronym: TGANephrotic

summary:
The thromboembolic risk is increased during the nephrotic syndrome (NS) with an incidence of deep vein thrombosis 15%, pulmonary embolism of 10-30% and renal vein thrombosis of 25-37%. There is a hemostatic imbalance with urinary leakage of anticoagulant factors and increased hepatic synthesis of procoagulant factors, platelet hyperaggregability and a decrease in fibrinolytic activity. However, the identification of patients requiring anticoagulant prophylaxis remains imprecise.The thromboembolic risk is higher when the NS is related to extramembranous glomerulonephritis comparatively to others glomerulopathies. The reason of this difference is not still known. This risk increase with SN's severity and therefore with the decrease of albuminemia. Moreover, few studies have evaluated anticoagulant treatment efficacy during a NS, which clinical benefit depends also on hemorrhagic risk specific of each patient. Thus, the determination of the thrombotic risk and the modalities of anticoagulation are variable and perfectible during the NS.

We propose to use the thrombin generation test (TGT) to quantify the thromboembolic risk in patients with a NS and to follow its evolution during prophylactic anticoagulation and after remission of NS.

location_facility: Service de Néphrologie et Dialyses, Hôpital Tenon


title: Impact of a Standardized Music Therapy Protocol on the Quality of Life of Patients With Abnormal Movements Treated With Continuous Electrical Neuromodulation (Music-QOL)

acronym: Music-QOL

summary:
The study of the impact of music on emotional, motor and cognitive aspects remains recent. Music therapy has experienced a major boom over the last half century thanks to neuroradiological techniques for investigating the brain, and in particular in vivo functional MRI. Brain imaging has also made it possible to highlight and analyse certain activations of the networks concerned during the passive listening of music (receptive music therapy) but also during the playing of a musical instrument and/or the use of the voice (active music therapy). The accumulated data in music neurophysiology is now considerable [1]. Music therapy has thus been associated with motor rehabilitation in the case of acquired (stroke) and/or degenerative (Parkinson's disease) pathologies and has also been proposed as a means of pain relief. However, although proposed in the middle of the 20th century as a potentially therapeutic tool, music therapy has not managed to prove sufficiently effective to be validated in medicine. One of the limitations remains the intervention of numerous subjective factors, notably in the establishment of "protocols" and the absence of standardisation in their very structures.

Each year, the "Resistant Brain Pathology" unit of the Department of Neurosurgery takes care of more than a hundred patients who have benefited from treatment with Continuous Electrical Neuromodulation (CEN) in order to respond to a motor symptomatology that is resistant to the usual treatments. The benefits of DBS in the management of abnormal movements have been demonstrated [2]. However, this symptomatic treatment does not exclude a worsening of the underlying pathology over time, thereby increasing latent anxiety and promoting the fragility of otherwise severely disabled patients. The management of chronic diseases requires the expertise of a multidisciplinary team so that each aspect contributing to the quality of life of patients can be assessed and supported as best as possible.

In order to improve the quality of life of our patients, a music therapy unit has been established within the multidisciplinary neurosurgery department for two years now. The clinical music therapist attached to the unit has a dedicated room, offering a sensory environment conducive to relaxation and including all the necessary comfort. A standardised protocol for the conduct of the sessions, the organisation and choice of music in direct relation to the different emotions explored on the basis of the permanent perception of heartbeats was developed on the basis of the Webb & all study [3]. When a patient is immersed in a sound bath, identical to that perceived in utero, it would seem that this potentiates the benefits expected from music therapy sessions [3].

Our approach, although empirical, shows a decrease in anxiety and an increase in well-being in about fifty patients. Our observations support those highlighted in the literature in other pathologies [4] and encourage the use of this approach as a preamble to more specific explorations, in particular the catalysis of certain motor behaviours.

This project is therefore in line with this approach and continuity.

The investigators thus hypothesize that participation in a standardized music therapy protocol (active, receptive and psychomusical relaxation) against a background of regular heartbeats improves the quality of life of the operated patients by acting in particular on a reduction of anxiety and depressive symptoms.

To our knowledge, music therapy has never been proposed in a standardised way to patients with multiple disabilities, operated on and cared for over the long term in a functional neurosurgery department. This approach remains non-invasive and attractive in an often anxiety-provoking hospital context.

primary_purpose: Supportive Care

ReferenceCitation: Sihvonen AJ, Sarkamo T, Leo V, Tervaniemi M, Altenmuller E, Soinila S. Music-based interventions in neurological rehabilitation. Lancet Neurol. 2017 Aug;16(8):648-660. doi: 10.1016/S1474-4422(17)30168-0. Epub 2017 Jun 26.

ReferenceCitation: Coubes P, Roubertie A, Vayssiere N, Hemm S, Echenne B. Treatment of DYT1-generalised dystonia by stimulation of the internal globus pallidus. Lancet. 2000 Jun 24;355(9222):2220-1.

ReferenceCitation: Ribeiro MKA, Alcântara-Silva TRM, Oliveira JCM, Paula TC, Dutra JBR, Pedrino GR, Simões K, Sousa RB, Rebelo ACS. Music therapy intervention in cardiac autonomic modulation, anxiety, and depression in mothers of preterms: randomized controlled trial. BMC Psychol. 2018 Dec 13;6(1):57. doi: 10.1186/s40359-018-0271-y.

ReferenceCitation: Hole J, Hirsch M, Ball E, Meads C. Music as an aid for postoperative recovery in adults: a systematic review and meta-analysis. Lancet. 2015 Oct 24;386(10004):1659-71. doi: 10.1016/S0140-6736(15)60169-6. Epub 2015 Aug 12. Review. Erratum in: Lancet. 2015 Oct 24;386(10004):1630.

ReferenceCitation: Lord VM, Hume VJ, Kelly JL, Cave P, Silver J, Waldman M, White C, Smith C, Tanner R, Sanchez M, Man WD, Polkey MI, Hopkinson NS. Singing classes for chronic obstructive pulmonary disease: a randomized controlled trial. BMC Pulm Med. 2012 Nov 13;12:69. doi: 10.1186/1471-2466-12-69. Erratum in: BMC Pulm Med. 2014;14:181.

location_facility: Unité Pathologies Cérébrales Résistantes (UPCR) - Département de Neurochirurgie - Gui de Chauliac

intervention_type: Behavioral


title: Relation Between Cortical Activation and Graded Force Level During Robot-assistance Walking in Healthy People : A Functional Near-infrared Spectroscopy Neuroimaging Study.

acronym: ExoNIRS

summary:
Background. Force control is one of the major parameter of motor activity. There is few study concerning the cortical activity imply for different levels of force during gait.

Objective. To investigate cortex activation while walking an exoskeleton with 4 levels of guidance force in healthy controls.

Methods. The investigators acquired near-infrared spectroscopy (fNIRS) with a 20 channels device (Brite 24® ; Artinis) covering bilaterally most motor control brain regions during exoskeleton walking at different level of force (100 %, 50% aid, 0 % aid and 25 % of resistance) in 24 healthy controls. The investigators measured variations of oxyhemoglobin (HbO2) and deoxyhemoglobin (HbR). The technique was optimized by the use of reference channels (to correct for superficial hemodynamic interference).

primary_purpose: Health Services Research

ReferenceCitation: Chen WL, Wagner J, Heugel N, Sugar J, Lee YW, Conant L, Malloy M, Heffernan J, Quirk B, Zinos A, Beardsley SA, Prost R, Whelan HT. Functional Near-Infrared Spectroscopy and Its Clinical Application in the Field of Neuroscience: Advances and Future Directions. Front Neurosci. 2020 Jul 9;14:724. doi: 10.3389/fnins.2020.00724. eCollection 2020. Review.

ReferenceCitation: Kim H. Corrigendum to "Cerebral hemodynamics predicts the cortical area and coding scheme in the human brain for force generation by wrist muscles" [Behav. Brain Res. 396 (2021) 112865]. Behav Brain Res. 2021 Feb 26;400:113054. doi: 10.1016/j.bbr.2020.113054. Epub 2020 Dec 17.

lead_sponsor: Centre Hospitalier Régional d'Orléans


title: Study of a Management Strategy of Functional Bowel Disordes Related to Irritable Bowel Syndrome (IBS) With a Mixture of 8 Microbiotic Strains

summary: The aim of this study is to determine the impact of a 10-day treatment with Lactichoc® on irritable bowel syndrome.

lead_sponsor: PiLeJe

location_facility: General practitioners or gastroenterologists consulting in french private offices

intervention_type: Dietary Supplement


title: Assessment of Spine Rehabilitation Program Using Spine Flexion and Extension Full Active Range of Motion for Patients With Chronic Low Back Pain : a Monocentric Prospective Cohort Study

acronym: REACTIVE

summary: The main objective of this study is to assess efficacy of a spine rehabilitation program, using spine flexion and extension full active range of motion, on physical disability of patients with chronic low back pain.

lead_sponsor: Groupe Hospitalier de la Region de Mulhouse et Sud Alsace


title: Assessment of Flecainide to Lower the Patent Foramen Ovale Closure Risk of Atrial Fibrillation or Tachycardia

acronym: AFLOAT

summary:
About 30% of ischemic strokes are cryptogenic. Patent Foramen Ovale (PFO) is present in about 25% of the general population. In cryptogenic strokes, PFO has been shown to be overrepresented and recent intervention studies have confirmed that PFO has a causal link with stroke. In patients with recent cryptogenic stroke, these randomized studies have shown at least 50%-reduction of recurrent neurological events after PFO percutaneous closure compared with medical therapy alone. At the The risk of AF reported in these studies in certainly largely underestimated as only symptomatic and recorded episodes of AF have been declared. Patients often report palpitations without a dia gnosis of AF made on the ECG or a Holter. Long term ECG monitoring provides more accurate data on AF incidence.

Administration of flecainide has been shown to be effective in preventing AF and may be useful in preventing these AF episodes after PFO closure.

To the knowledge of the investigators, there is no study assessing the efficacy of any antiarrhythmic drug in the prevention of AF after PFO closure. AFLOAT will be the first randomized study to possibly validate flecainide to prevent AF in these patients.


title: A Phase I/II, Multicenter, Randomized, Double-blind, Placebo Within-patient Controlled, First-in-human (FIH) Proof of Concept (PoC) Study to Evaluate the Safety and Efficacy of Topically Applied SXR1096 Cream in Patients With Netherton Syndrome (NS)

summary: In this phase I/II trial a topical skin cream with the active substance SXR1096 will be tested in patients with Netherton syndroms, a rare inflammatory skin disease. SXR1096 is a specific and potent protease inhibitor that can inhibit the proteases kallikrein 5, 7 and 14 - all recognised as up-regulated and causing the disease state in Netherton syndrome patients. Patients will be treated for one month with active cream and placebo cream at different areas of the skin.

lead_sponsor: Sixera Pharma


title: Observational Study for the Evaluation of Long Term Performance and Safety of the HLS KneeTec Deep Dish Prosthesis in Total Knee Arthroplasty

summary: The aim of this study is to assess the long-term performance and safety of HLS KneeTec Deep Dish knee prosthesis when used in standard medical practice

status: Active, not recruiting

lead_sponsor: Corin


title: Screening for Renal Complications in Children and Young Adults With Major Sickle Cell Disease

acronym: NEPHRO-DREPA

summary:
Sickle cell disease is the subject of targeted neonatal screening (carried out when one of the two parents is from an endemic country - sub-Saharan Africa, South-East Asia, Central America, the Caribbean) during the Guthrie test. Haemolysis, which results from the abnormality of the haemoglobin, and the vascular activation it causes, are responsible for multiple organ damage. Major sickle cell syndromes (MSC), by several mechanisms, are responsible for a wide range of renal damage, culminating in end-stage renal failure at an average age of 45 years and with an average survival of 3 years beyond ESRD.

The various renal disorders are : glomerular hyperfiltration and then glomerulosclerosis; tubular dysfunction, especially proximal and distal hyposthenuria (a factor in enuresis); papillary necrosis, renal infarction, episodes of acute renal failure during vaso-occlusive crises; dysregulation of the renin-angiotensin system with early arterial hypertension and, more rarely, extra-membranous glomerulonephritis. In the early stages of these conditions, simple paraclinical tests can identify them before the appearance of specific clinical signs.

In patients suffering from MDS, the HAS (High Authority of Health) recommends an annual check-up carried out in a Competence Centre. According to the HAS recommendations for annual surveillance, in addition to the search for other organic complications, for renal pathology, only microalbuminuria and renal ultrasound are recommended. However, as the literature shows, microalbuminuria and ultrasound only detect some of these renal disorders and at a very late stage. A large number of publications in adults and, to a lesser degree, in children, demonstrate the correlation between the frequency of acute complications of sickle cell disease (episodes of haemolysis, etc.) and the occurrence of kidney damage.

lead_sponsor: Centre Hospitalier Universitaire de Nice


title: Weaning From Nasal High Flow Therapy: an Explorative Study Assessing the Usefulness of the ROX Index to Predict Outcome of the Weaning Process in Combination With a Withdrawal Trial

summary: Nasal high flow is widely used in critically ill patients admitted to the intensive care unit (ICU) for acute hypoxemic respiratory failure. It has been shown to improve patient comfort, increase oxygenation and reduce need for intubation in some patients. The Respiratory Oxygenation (ROX) index has been established as a simple tool to help clinicians identify those patients who will succeed and those who will fail under nasal high flow and therefore predict the need for intubation. However, when nasal high flow therapy is successful, little is known as to how and when weaning of this device should be performed and what are the predictors of a safe withdrawal of the device. The objectives of this retrospective exploratory study are to identify a cut-off value of the ROX index predictive of success of the withdrawal trial, to describe a one-year use of the withdrawal trial; to describe the ROX value closest to weaning from nasal high flow, and to identify factors associated with success or failure of the withdrawal trial from nasal high flow therapy in patients receiving nasal high flow therapy.

ReferenceCitation: Ricard JD, Roca O, Lemiale V, Corley A, Braunlich J, Jones P, Kang BJ, Lellouche F, Nava S, Rittayamai N, Spoletini G, Jaber S, Hernandez G. Use of nasal high flow oxygen during acute respiratory failure. Intensive Care Med. 2020 Dec;46(12):2238-2247. doi: 10.1007/s00134-020-06228-7. Epub 2020 Sep 8. Review.

ReferenceCitation: Roca O, Caralt B, Messika J, Samper M, Sztrymf B, Hernández G, García-de-Acilu M, Frat JP, Masclans JR, Ricard JD. An Index Combining Respiratory Rate and Oxygenation to Predict Outcome of Nasal High-Flow Therapy. Am J Respir Crit Care Med. 2019 Jun 1;199(11):1368-1376. doi: 10.1164/rccm.201803-0589OC.

ReferenceType: result

ReferenceCitation: Rodriguez M, Thille AW, Boissier F, Veinstein A, Chatellier D, Robert R, Le Pape S, Frat JP, Coudroy R. Predictors of successful separation from high-flow nasal oxygen therapy in patients with acute respiratory failure: a retrospective monocenter study. Ann Intensive Care. 2019 Sep 11;9(1):101. doi: 10.1186/s13613-019-0578-8.

lead_sponsor: Hôpital Louis Mourier

location_facility: Hôpital Louis Mourier, Assistance Publique - Hôpitaux de Paris


title: Effect of Intranasal Oxytocin on Dysphagia Related to Oropharyngo-oesophageal Dysmotility in Children and Adolescents With Prader-Willi Syndrome: a Phase 3 Study

acronym: DYSMOT

summary:
This phase 3 is designed to test the effectiveness of intranasal Oxytocin on Prader Willi Syndrome (PWS).

This is a prospective, multicentre, randomised, double-blind, Phase 3 clinical study planned to include around 36 PWS patients aged 2-17 years and 5 months.


title: Optimization of the Role of Action Observation in the Post-operative Rehabilitation of the Total Knee Prosthesis

acronym: LOARAL 2

summary: The LOARAL 2 project concerns patients who have undergone total knee arthroplasty to treat symptomatic osteoarthritis. Patient will be divided into three groups: a control group where patients will do standard rehabilitation associated with the judgments of videos represented non-human action and two experimental groups where patients will do standard rehabilitation associated with the judgement of human point-light display. The aim of this study is to measure the benefits of attentional focus and sex correspondence in the use of point-light display for the rehabilitation of patients with a total arthroplasty of the knee.

lead_sponsor: Poitiers University Hospital

location_facility: Centre Hospitalier Universitaire Poitiers


title: Efficiency of Chewing-gum to Reduce the Duration Postoperative Ileus: a Randomized Controlled Study

acronym: CHEWIP

summary:
Postoperative ileus (POI) is a serious complication after surgery. While it complicates all type of surgery, it is more frequent after abdominal surgery (especially bowel or colorectal surgery).

Many studies aim to reduce the occurence of POI without efficiency. The aim of this study is to assess the efficiency of the vagal stimulation, by the mean of chewing, to reduce the duration of POI.

lead_sponsor: University Hospital, Angers


title: Local Inflammation in Arrhythmogenic Right Ventricular Cardiomyopathy

acronym: LI-ARVC

summary: The understanding of ARVC pathophysiology remains incomplete. Several clues indicate that disease progression is mediated through inflammation. The present study aim to document the feasibility of detecting the potential presence of intracardiac local inflammatory components in patients with ARVC.

design_allocation: Non-Randomized

lead_sponsor: University Hospital, Toulouse

intervention_type: Biological


title: Evaluation and Modeling of the Effect of G-CSF on the Evolution of Polynuclear Neutrophils During Dense Dose Epirubicin-Cyclophosphamide Regeneration

acronym: EMEG-ECDD

summary:
Patients including of localized breast cancer will require chemotherapy treatment with epirubicin - cyclophosphamide (EC) followed by treatment with docetaxel or paclitaxel. In addition to this chemotherapy, the investigator will prescribe injections of granulocyte growth factors (G-CSF), to stimulate the growth of white blood cells. Patients will be randomized to either a peg-G-CSF arm or a G-CSF arm, prescribed at different times.

The aim is to determine whether one of the two treatment regimens best limits the risk of a decrease in white blood cells

lead_sponsor: Centre Georges Francois Leclerc


title: Hepatic Encephalopathy Prevention With Polydextrose After TIPS: Pilot Study

acronym: POEME

summary:
TIPS is a standard for the treatment of portal hypertension related complications. However, it remains at risk of HE after TIPS (around 40% the first year). Dysbiosis plays a key role in pathophysiology of HE.

Polydextrose (PDX) is consider as a prebiotic. Preliminary studies showed that PDX:

modified gut microbiota, enhancing "good bacteria"
improved gut permeability and immunity in 2 experimental models: infarction and colitis.

The aim of this study is to assess PDX efficacy to prevent HE during the first 6 months after TIPS in cirrhotic patients.

ReferenceCitation: Bureau C, Métivier S, D'Amico M, Péron JM, Otal P, Pagan JC, Chabbert V, Chagneau-Derrode C, Procopet B, Rousseau H, Bosch J, Vinel JP. Serum bilirubin and platelet count: a simple predictive model for survival in patients with refractory ascites treated by TIPS. J Hepatol. 2011 May;54(5):901-7. doi: 10.1016/j.jhep.2010.08.025. Epub 2011 Feb 18.

ReferenceCitation: European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018 Aug;69(2):406-460. doi: 10.1016/j.jhep.2018.03.024. Epub 2018 Apr 10. Erratum in: J Hepatol. 2018 Nov;69(5):1207.

ReferenceCitation: Bureau C, Thabut D, Oberti F, Dharancy S, Carbonell N, Bouvier A, Mathurin P, Otal P, Cabarrou P, Péron JM, Vinel JP. Transjugular Intrahepatic Portosystemic Shunts With Covered Stents Increase Transplant-Free Survival of Patients With Cirrhosis and Recurrent Ascites. Gastroenterology. 2017 Jan;152(1):157-163. doi: 10.1053/j.gastro.2016.09.016. Epub 2016 Sep 20. Erratum in: Gastroenterology. 2017 Sep;153(3):870.


title: The Value of Positive Pressure Extubation in Reducing Postoperative Desaturation Episodes in Adults Undergoing Abdominal Surgery

acronym: EXTUBPOS

summary: Single-center, prospective, controlled, parallel, randomized, single-blind study comparing the conventional extubation technique to two positive pressure extubation techniques on postoperative desaturations

lead_sponsor: University Hospital, Lille


title: Implementation of a 12-week Adapted Physical Activity (APA) Program in People Suffering From Chronic Insomnia.

summary: One third of men and women are not satisfied with their sleep. A non-drug countermeasure to improve sleep in insomniacs could be adapted physical activity (APA). However, research is needed because the literature is limited and the few studies are most often based on subjective data with a great methodological disparity. Within the framework of the care pathway of Dr ARON's patients, sleep doctor at the Sommeil Morphée Center of the Grande Synthe Polyclinic (59), the objective of this project is to make an APA program more reliable in order to improve sleep, to understand the underlying mechanisms and to include APA in the therapeutic management.

lead_sponsor: Universite du Littoral Cote d'Opale


title: Evolution of the SURvival of Patients With SEzary Syndrome (SS) Over the 1998-2020 Period and Its Association With the Early Use of Therapeutic Monoclonal Antibodies

acronym: SURPASSe

summary:
Sezary syndrome (SS) is a rare, aggressive and advanced form of cutaneous T lymphoma with a poor prognosis (5-year survival rate varying between 24% and 52%). The treatments are only suspensive with short-term remissions. For the past fifteen years, therapeutic approaches have been based on depleting monoclonal antibodies (anti-CD52, anti-CCR4, anti-KIR3DL2, anti-CD70), or antibody-drug conjugates (anti-CD30). But while the efficacy of mogamulizumab on progression-free survival was reported in the phase III study, no study on a large cohort has compared the current overall survival of patients with Sezary syndrome to that before the era of monoclonal antibodies. In this context, we propose to report a large series of patients with Sézary syndrome in order to compare the current survival of patients with that of the pre-monoclonal antibodies era (1998-2003).

The objective of this study is to assess the evolution of the overall survival of patients with Sezary syndrome since the early use of therapeutic monoclonal antibodies. The underlying hypothesis of this study is that the use of therapeutic monoclonal antibodies has improved the prognosis of these patients. Patients included in this retrospective study are patients with a Sezary syndrome diagnosed between 1998 and 2020.

lead_sponsor: Assistance Publique - Hôpitaux de Paris

location_facility: Hôpital Saint-Louis, Service de Dermatologie


title: Smart Bra for Diagnosing Breast Cancer: Pilot Study - CBRA

acronym: CBRA

summary: This project aims to assess the ability of a portable and connected medical device to detect breast abnormalities, for breast cancer screening. It will accelerate technological progress in the face of breast cancer.

primary_purpose: Screening

lead_sponsor: Hopital Nord Franche-Comte


title: Aggressive Versus Restrictive Initiation of Antimicrobial Treatment in Critically Ill Patients With Suspected Ventilator Acquired Pneumonia Without Severity : a Before and After Observational Study

acronym: DELAVAP

summary: This retro-prospective monocentric observational study compare the impact of the implementation of a restrictive (delayed) versus aggressive (immediate) antibiotic strategy for Ventilator Acquired Pneumonia suspicion without severity symptoms.

lead_sponsor: Nantes University Hospital


title: Are Mast Cells Involved in Autoinflammatory Diseases

acronym: INFLAMAST

summary: Autoinflammatory diseases (AID) are caused by innate immunity dysregulation. AID pathophysiology is only partly understood, especially in the case of unclassified AID. Mast cells (MC) are innate immune cells associated with a spectrum of disease between systemic mastocytosis and mast cell activation syndrome. The implication of MC has been shown in cryopyrin associated periodic syndrome (CAPS).Our aim is to evaluate the involvement of MC in AID by assessing clinical and biological signs of MC activation and studying cutaneous and digestive biopsies.


title: Evaluation of the Impact of COMORBIDities on Morbidity and Mortality After Radical Cystectomy for Cancer Using a Predictive Method With Artificial Intelligence

acronym: COMORBID-AI

summary:
Clinician and the multidisciplinary team meeting in oncologic urology (MMO) play a key-role in the decision making. An unexplained surgeon attributable variance, probably linked to the subjective "eyeball test" effect, was identified as a strongest factor underlying non-compliance with guide line recommendations in the management of bladder cancer. So high-quality studies that identify barriers and modulators (such as comorbidities) of provider-level adoption of guidelines and how comorbidities are associated in making therapeutic choice and their impact in bladder cancer specific survival and overall survival, are crucial. To identify patients at high risk of early death, and to improve specific guideline for treatment might be decisive.

In order to assess survival, where mortality events compete, it will be more appropriate to compute a Cumulative Incidence Function (namely CIF). The investigators will compare outcomes across patient populations to obtain information to improve clinical decision-making. Such learning will be done through the use of neural networks or by applying population-based approaches, such as Genetic Algorithms (GA), Ant Colony Systems (ACS) and Particle Swarm Optimization (PSO), using as a four-stage based approach.

First, the investigators propose a "pretopology space" in order to study a dynamic phenomenon. Second, the investigators recall that the K-means approach remains one of the most used approaches for classifying a set of elements (patients / persons / others) into K (disjunctive) clusters. Third, the investigators propose a learning pretopology space for enhancing the clustering. Such an approach can be assimilated in spirit to one applied with high success on deep learning. Fourth and last, the investigators propose a reactive method that is able to include some new elements or remove some contained elements

lead_sponsor: Centre Hospitalier Universitaire, Amiens


type: Registry Identifier

title: Screening for 3-D Visual Disorders in Preschool Children, VISION Study

acronym: VISION

summary: Visual screening is necessary among pre-school children as they found themselves in a critical period of visual developement. To date, there are no national vision screening program that has been implemented nationwide. Vision is a pilot feasibility multicentric cluster study comparing the sensitivity of "AFSOP 3 dimensional visual screening protocol in a population of 3 to 4-year-old pre-school children conducted in 4 kindergarten preschools in Paris with gold-standard ophthalmic examination confirmation.


title: New Therapeutic Approach to Cure Rheumatoid Arthritis

acronym: CURE RA

summary:
Rheumatoid arthritis (RA) is an autoimmune disease characterized by the presence of autoantibodies directed against citrullinated proteins, called ACPAs. These antibodies are very specific to RA, and the severity of the disease is closely correlated with the level of these ACPAs, even though they appear much earlier than the clinical signs. Current treatments by biotherapies are effective but only treat the inflammatory symptoms of the disease or, on the contrary, induce a global immunosuppression with a depletion of all B lymphocytes.

Contrary to the current approaches, the CURE RA project proposes a double innovative character:

The project aims at specifically destroying B lymphocytes expressing / or secreting ACPAs for a more specific approach to RA, without inducing immunosuppression.
The new therapeutic molecule is entirely original and has no equivalent at present, it uses the target antigens of autoantibodies, the citrullinated peptides, as tools to destroy the pathogenic B cells that express/produce these autoantibodies.

lead_sponsor: University Hospital, Montpellier


title: Weight-Bearing Cone Beam CT Arthrogram of the Ankle: a Lower Radiation Dose Technique to Evaluate Osteo-chondral Lesions or Cartilage Lesions: Is it the Future of the arthroCT?

acronym: Arthro-CBCT

summary: This study aims to compare weight-bearing Cone Beam CT arthrogram and conventional CT arthrogram in assessement of patients with ankle osteo-chondral or cartilage lesions.

ReferenceCitation: Lopes R, Geffroy L, Padiolleau G, Ngbilo C, Baudrier N, Mainard D, Benoist J, Leiber Wackenheim F, Cordier G, Dubois Ferriere V, Freychet B, Barbier O, Amouyel T. Proposal of a new CT arthrographic classification system of osteochondral lesions of the talus. Orthop Traumatol Surg Res. 2021 Oct;107(6):102890. doi: 10.1016/j.otsr.2021.102890. Epub 2021 Mar 10.

ReferenceCitation: Grunz JP, Pennig L, Fieber T, Gietzen CH, Heidenreich JF, Huflage H, Gruschwitz P, Kuhl PJ, Petritsch B, Kosmala A, Bley TA, Gassenmaier T. Twin robotic x-ray system in small bone and joint trauma: impact of cone-beam computed tomography on treatment decisions. Eur Radiol. 2021 Jun;31(6):3600-3609. doi: 10.1007/s00330-020-07563-5. Epub 2020 Dec 5.

ReferenceCitation: Broos M, Berardo S, Dobbe JGG, Maas M, Streekstra GJ, Wellenberg RHH. Geometric 3D analyses of the foot and ankle using weight-bearing and non weight-bearing cone-beam CT images: The new standard? Eur J Radiol. 2021 May;138:109674. doi: 10.1016/j.ejrad.2021.109674. Epub 2021 Mar 20.

ReferenceCitation: Posadzy M, Desimpel J, Vanhoenacker F. Staging of Osteochondral Lesions of the Talus: MRI and Cone Beam CT. J Belg Soc Radiol. 2017 Dec 16;101(Suppl 2):1. doi: 10.5334/jbr-btr.1377.

location_facility: Radiological department, Raymond Poincaré hospital, APHP


title: Influence of Anthropometric Data, Shoulder Complex Muscle Strength, and Abdominal-lumbar Endurance in Closed Kinetic Chain Upper Extremity Stability Test

acronym: EPOLTEST 2

summary:
A previous study of the Closed Kinetic Chain Upper Extremity Stability Test (EPOLTEST) in a population aged 18 to 25 years isolated 3 main factors influencing the CKCUEST score: upper extremity span, weight, and sex of the individual. A predictive equation for the CKCUEST score was thus established and to date has a capacity to determine the real score of approximately 51%.

The results of this first study show that a certain number of variables have not been studied.

The purpose of this study, EPOLTEST 2, is to take into account the variables already studied on a larger population (18-50 years old) and to add an assessment of shoulder muscle strength and abdominolumbar endurance.

ipd_sharing: Yes

ipd_sharing_description: All collected data that underlie results in a publication

lead_sponsor: University Hospital, Brest


title: Prospective Evaluation of the Prognostic Impact of Measurable Residual Disease (MRD) Within a Phase III Study Comparing a Fixed Duration Therapy Versus Continuous Therapy With Daratumumab, Lenalidomide, and Dexamethasone for Relapsed Multiple Myeloma Requiring a First Salvage Treatment.

acronym: MRD-CONFIRM

summary: We propose to conduct an ancillary prospective evaluation of the impact of Dara-Len-Dex discontinuation after 2 years, on the persistence of MRD negativity in patients that were MRD negative at 2 years.

location_facility: Department of Hematology, Hospital Saint Antoine


title: Efficacy of ADW S-100 Ionized Water Nasal Spray in Decreasing SARS-Cov-2 Viral Load in Adults With High Viral Excretion by Nasopharyngeal Swabbing. Randomized, Double-blind, Placebo-controlled, Parallel Group Study.

summary:
A nasal spray based on Advanced Water S-100 ionized water would clean the nasal cavity, reduce the viscosity of the mucus and facilitate its elimination and the decongestion of the nose and the prevention of the seizure of the SARS-COV-2 to the epithelial cells of the nasal cavity In fact, a nasal spray based on Advanced Water S-100 ionized water would modify the electrostatic environment of all interactions ensuring this seizure. The negative ions (OH-) contained in Advanced Water S-100 compete with the negative ions of the heparan sulfate, which will destabilize this essential bond for the virus to enter the host cell. In addition, positively charged basic amino acids, in the presence of the basic pH of ADW S-100, will be neutralized by OH- ions which will prevent the formation of salt and hydrogen bridges mediating the formation of the protein S/ACE2 complex. The destabilization of all bonds governing the protein S/ACE2 association process will prevent the virus from entering cells and replicating.

The aim of this study is to evaluate whether the use of ADW S-100 ionized water nasal spray reduces the salivary and nasopharyngeal viral load during an 8-day follow-up of persons recently infected with SARS-Cov-2, and thus potentially decreases the risk of contamination of the entourage.

status: Terminated

ipd_sharing_description: Trial prematurely stopped as recruitment interrupted with less than 10% participants included

lead_sponsor: P & B Group


title: Cellular microRNA Signatures in Multiple Sclerosis

acronym: SEP-MIR

summary:
A limited number of studies on microRNA expression variation in immune cells have been reported in relapsing-remitting multiple sclerosis (RRMS). These studies have been performed mostly on a small scale and on whole blood mononuclear cells (PBMC).

In a number of cases, RRMS progresses to a severe secondary neurodegenerative form. In this context, it is important to look for biomarkers that could indicate the pathogenic activity of certain immune cell subpopulations.

lead_sponsor: Institut Pasteur

intervention_type: Genetic


title: The Role of IL-23 in Chronic Inflammatory Disease: Exploring the Cellular and Molecular Targets of IL-23 Signaling in Peripheral and Axial Spondyloarthritis

summary: This is a research study involving humans, of the interventional type with minimal risks and constraints (RIPH2). It is a bicentric, non randomized prospective study aiming to better understand the mechanisms of the response to anti-IL-23 biologics in Spondyloarthritis patients attending the rheumatology department of hospital Cochin and Saint Antoine (APHP).


title: Deep Sclerectomy vs Xen in Solo Procedure: Comparative Study, Efficacy and Safety Profile

acronym: SPXen

summary:
Glaucoma is the leading cause of irreversible blindness in the world and the second leading cause of blindness after cataract after the age of 50. Lowering intraocular pressure (IOP) is the only treatment option to prevent visual field degradation. While medical treatment and selective laser trabeculoplasty are considered first-line options in open-angle glaucoma, the surgical option is considered in patients who have uncontrolled IOP under maximal tolerated medical treatment. In this situation, trabeculectomy or deep nonperforating sclerectomy may be performed. Although it is uncertain whether SPNP is superior to trabeculectomy, which is considered the gold standard of surgery, SPNP is a procedure that offers a better quality of life and fewer intra- and postoperative complications. SPNP was first described by Zimmerman. It consists in peeling off the internal wall of Schlemm's canal and the juxta-canalicular trabeculum which represent the main resistances to the evacuation of the aqueous humor. The trabecular meshwork is left intact and acts as a filter membrane between the subconjunctival space and the anterior chamber. The addition of mitomycin (MMC) is necessary because it is associated with better IOP control and greater surgical success. Although postoperative procedures such as needling or Nd:YAG laser-assisted gonioponctures are often required, SPNP offers good long-term results in patients who are naïve to any filtering surgery.

Minimally invasive surgery has been used more and more over the last 10 years. It aims to reduce surgical complications in comparison to classical filtering procedures while respecting the eye's own anatomy. Several devices have been invented to increase aqueous humor elimination. They can be implanted ab-interno or ab-externo and can be implanted in the suprachoroidal space, in Schlemm's canal or in the subconjunctival space. The XEN gelstent (Allergan, Dublin, Ireland) is placed ab-interno between the subconjunctival space and the anterior chamber, either in combination with cataract surgery or as a solo procedure.

The aim of the study is to compare the surgical success of these 2 techniques. No study has ever compared these 2 surgeries in solo procedure. A recent retrospective trial compared them in combined procedures without showing significant differences in IOP reduction. Nevertheless, the short follow-up period of 9 months may have been insufficient to show a real difference.

ReferenceCitation: GBD 2019 Blindness and Vision Impairment Collaborators; Vision Loss Expert Group of the Global Burden of Disease Study. Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to VISION 2020: the Right to Sight: an analysis for the Global Burden of Disease Study. Lancet Glob Health. 2021 Feb;9(2):e144-e160. doi: 10.1016/S2214-109X(20)30489-7. Epub 2020 Dec 1. Erratum in: Lancet Glob Health. 2021 Apr;9(4):e408.

ReferenceCitation: Gazzard G, Konstantakopoulou E, Garway-Heath D, Garg A, Vickerstaff V, Hunter R, Ambler G, Bunce C, Wormald R, Nathwani N, Barton K, Rubin G, Buszewicz M; LiGHT Trial Study Group. Selective laser trabeculoplasty versus eye drops for first-line treatment of ocular hypertension and glaucoma (LiGHT): a multicentre randomised controlled trial. Lancet. 2019 Apr 13;393(10180):1505-1516. doi: 10.1016/S0140-6736(18)32213-X. Epub 2019 Mar 9. Erratum in: Lancet. 2019 Jul 6;394(10192):e1.

ReferenceCitation: Eldaly MA, Bunce C, Elsheikha OZ, Wormald R. Non-penetrating filtration surgery versus trabeculectomy for open-angle glaucoma. Cochrane Database Syst Rev. 2014 Feb 15;(2):CD007059. doi: 10.1002/14651858.CD007059.pub2. Review.

ReferenceCitation: Rulli E, Biagioli E, Riva I, Gambirasio G, De Simone I, Floriani I, Quaranta L. Efficacy and safety of trabeculectomy vs nonpenetrating surgical procedures: a systematic review and meta-analysis. JAMA Ophthalmol. 2013 Dec;131(12):1573-82. doi: 10.1001/jamaophthalmol.2013.5059. Review.

lead_sponsor: Groupe Hospitalier Paris Saint Joseph


title: Interest in the Use of Nasal High-Flow Oxygen Therapy (OptiFlow™) in Secondary Transport of COVID-19 Positive Patients

summary:
Since the beginning of COVID-19 pandemic situation, several modes of ventilation have been tried to correct the hypoxaemia induced by SARS-CoV-2 virus. A few recent studies have concluded that high-flow nasal oxygen therapy (OptiFlow™) is beneficial in COVID-19. All mainly conclude that the use of OptiFlow™ avoid intubations and decrease hospitalization duration in critical care services.

At the emergency medical service 83 (SAMU 83), it has been decided to extend this ventilation mode during patient secondary transfers (transfer from an intensive care unit/other hospital unit/emergency department to another hospital's intensive care unit).

The emergency medical service 83 has equipped its intensive-care ambulances with OptiFlow™ in order not to interrupt this ventilation mode during transport.

The hypothesis is that patients with a severe respiratory form of COVID-19 transported from one health facility to another by the emergency medical service 83 on high-flow nasal oxygen therapy has a reduced risk of intubation compared to the other modes of non-invasive ventilation (NIV) and High Concentration oxygen Masks (HCM).

lead_sponsor: Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer

location_facility: Centre Hopitalier Intercommunal Toulon - La Seyne sur Mer


title: Spondyloarthritis and Nutrition

acronym: SANUT

summary:
The food composition and consumption of certain foods could be associated with a higher or lower inflammatory activity of spondyloarthritis and consequently changes in the quality of life of patients. This has been shown in other chronic inflammatory disease.

In order to highlight a profile or nutritional profiles associated with the activity of the disease, we chose to carry out observational pilot study using a qualitative food survey, which will be submitted to all patients with spondyloarthritis. The general demographic data and the data of the disease will be collected by the investigating physician at the same time, as well as possible confounding factors: comorbidities, physical activity, treatments.

lead_sponsor: University Hospital, Limoges


title: IMPACT OF SURGICAL EXPERIENCE ON RENAL TRANSPLANT COMPLICATIONS

acronym: IMPACT

summary:
Kidney transplantation (KT) failure could be due to surgery dependent factors and particularly surgeon's experience.

Objective: To assess the impact of the surgeon's experience on the post-operative outcomes to know if it safe for young surgeons to perform it.

ipd_sharing_description: No sharing data plan was established.

lead_sponsor: Centre Hospitalier Universitaire de Nice


title: Prospective, Randomised, Controlled Pilot Study Evaluating the Impact of Loco-regional Analgesia Following Placement of Erector Spinae Plane Catheter in Addition to Systemic Analgesia in Patients With Thoracic Trauma

acronym: ERECTRAUTHO

summary:
The management of analgesia is the key issue in the management of a thoracic trauma patient to prevent respiratory complications.

A multimodal approach is recommended but the question of the most suitable loco-regional analgesia technique remains. It must combine effectiveness and simplicity with the least risk to the patient. Today, epidural analgesia is the technique of choice, but it has certain disadvantages: difficulties in performing it at the thoracic level, undesirable effects, complications, and numerous contraindications.

The investigator propose to carry out a single-centre, prospective, randomised, controlled pilot study evaluating the impact of loco-regional analgesia following the placement of erector spinae plane catheter in addition to systemic analgesia in patients with thoracic trauma.

The aim is to demonstrate the effectiveness of this technique, which has fewer disadvantages than epidural analgesia. The interest of this study is thus to decrease the respiratory morbidity of thoracic trauma patients by avoiding a maximum of complications.

lead_sponsor: Centre Hospitalier Departemental Vendee


title: Improving Carbapenemase-Producing Organism (CPO) and Vancomycin-Resistant Enterococcus (VRE) Management With BD Solutions

acronym: CPO-VRE

summary:
Emergence of vancomycin-resistant enterococci (VRE) and carbapenemase-producing enterobacteria (CPE) is nowadays a major public health concern worldwide. VRE and CPE are referred to as Emerging eXtensively Drug Resistant bacteria (eXDR).

A better, faster and more accurate identification of VRE and CPE would allow faster appropriate therapy for patients and/or infection control strategies. Faster appropriate therapy could improve mortality rates, length of stay, and other patient outcomes as well as hospital costs. BD offers a variety of products, services and solutions designed to increase efficiency, streamline processes, and deliver high quality and consistent results with improved turnaround time.

The primary objective of this study will be to measure the impact of the BD CPO and VRE PCRs on the turnaround time for eXDR positive detection.

Study will collect criteria and compared several outcomes before and after the implementation of the BD solutions for the detection of eXDR.

This is a non-interventional research with a before/after design.

The study therefore consists of two periods:

1st period of 6 months during which only the current detection technique will be used.
2nd period of 6 months after implementation of the PCR solution (CPO and VRE) of the BD company in parallel with the usual screening technique.

Advantages of using molecular assays to screen for eXDR include labor savings, faster turnaround time, and higher sensitivity than culture-based methods.

In trying to reduce testing time, investigators should have better control of the eXDR transmission. this should reduce patient-to-patient transmissions. The number of contact patient in case of one positive screening should decrease. The number of days where patients are unnecessary placed in preemptive isolation should also decrease.

Moreover, PCR will be use in first intention and only positive samples in PCR will be cultivated; For the laboratory, technician time saving is expected given the simplicity of the PCRs. Plate readings at 24 and 48h will be limited to a few samples. Investigators also expect a significant gain in financial terms for hospital by performing a medico-economic analysis. According to the shorter time for getting results using BD solution in diagnosing patients at risk, investigators then assume that a shorter time in making clinical decision will be a normal consequence, and will imply a better relevant organization of care with lower real costs.

ReferenceCitation: Zilberberg MD, Shorr AF, Micek ST, Vazquez-Guillamet C, Kollef MH. Multi-drug resistance, inappropriate initial antibiotic therapy and mortality in Gram-negative severe sepsis and septic shock: a retrospective cohort study. Crit Care. 2014 Nov 21;18(6):596. doi: 10.1186/s13054-014-0596-8.

ReferenceCitation: Bilavsky E, Schwaber MJ, Carmeli Y. How to stem the tide of carbapenemase-producing enterobacteriaceae?: proactive versus reactive strategies. Curr Opin Infect Dis. 2010 Aug;23(4):327-31. doi: 10.1097/QCO.0b013e32833b3571. Review.

ReferenceCitation: Zilberberg MD, Nathanson BH, Sulham K, Fan W, Shorr AF. 30-day readmission, antibiotics costs and costs of delay to adequate treatment of Enterobacteriaceae UTI, pneumonia, and sepsis: a retrospective cohort study. Antimicrob Resist Infect Control. 2017 Dec 6;6:124. doi: 10.1186/s13756-017-0286-9. eCollection 2017.

ReferenceCitation: Lepelletier D, Berthelot P, Lucet JC, Fournier S, Jarlier V, Grandbastien B; National Working Group. French recommendations for the prevention of 'emerging extensively drug-resistant bacteria' (eXDR) cross-transmission. J Hosp Infect. 2015 Jul;90(3):186-95. doi: 10.1016/j.jhin.2015.04.002. Epub 2015 Apr 24. Review.

ReferenceCitation: Mak A, Miller MA, Chong G, Monczak Y. Comparison of PCR and culture for screening of vancomycin-resistant Enterococci: highly disparate results for vanA and vanB. J Clin Microbiol. 2009 Dec;47(12):4136-7. doi: 10.1128/JCM.01547-09. Epub 2009 Oct 21.

ReferenceCitation: Holzknecht BJ, Hansen DS, Nielsen L, Kailow A, Jarløv JO. Screening for vancomycin-resistant enterococci with Xpert® vanA/vanB: diagnostic accuracy and impact on infection control decision making. New Microbes New Infect. 2017 Jan 12;16:54-59. doi: 10.1016/j.nmni.2016.12.020. eCollection 2017 Mar.

lead_sponsor: University Hospital, Grenoble


title: fNIRS-based Neurofeedback Intervention for Cognitive Control Improvement in Emotional Overeating

acronym: Cemov

summary:
Emotional overeating is characterized by an excessive food intake in the context of intense emotional situations, such as acute stress one. Emotional overeating, as a behavioral trait, can increase the risk of to develop eating disorders or eating-related diseases, such as metabolic syndrome, obesity, type-2 diabetes. Recently, imaging modalities, such as magnetic resonance imaging (MRI) and electro-encephalography (EEG), have been adapted in order to perform neurofeedback consisting on presenting the brain activity instantaneously to the participant, that give him the possibility to modify this activity by his own mean. Neurofeedback has already shown some efficacy, either with explicit or implicit instruction.

Compared with functional MRI (fMRI), functional near infra-red spectroscopy (fNIRS) is easy to handle, less expensive, and does not require a lying position. fNIRS is consequently more adapted for repeated acquisitions. Neurofeedback has already shown some promising results for neurological and psychiatric diseases. For mental states and emotion regulation, neurofeedback targeting the prefrontal cortex (PFC) has also shown promising outcomes. In this project, the investigators want to assess the effect of neurofeedback targeting the dorsolateral PFC (dlPFC) in a population of young adult women presenting emotional overeating. The investigators aim to improve the cognitive control and to reduce the episodes of emotional overeating in order to prevent the occurrence of subsequent pathologies.

The intervention effect will be characterized with: (i) fMRI in order to evaluate the effect on cognitive control (with resting state fMRI or rsMRI) and on the reward system; (II) questionaries directly and one month after intervention in order to assess the behavioral effect.

Besides an expected effect on emotional overeating, the investigators will evaluate whether an improvement of cognitive control can also promote positive effect on other behavioral traits that could lead to some pathologies such as food addiction.

As a prerequisite to this study on emotional overeating (study B), the investigators will firstly validate on healthy subjects (study A) a reward anticipation fMRI task, which will be further used in study A in order to characterized the effect of neurofeedback on the reward system.

lead_sponsor: Rennes University Hospital


title: HEMolyse and Organ Damage imPROvement in Sickle Cell Disease by VoxElotor. An Open-label One Stage Phase II Design

acronym: HEMOPROVE

summary:
Intro:

Sickle cell disease is a genetic disorder caused by a mutation of the β hemoglobin called HbS, which causes red blood cell (RBC) abnormalities responsible for hemolysis, mainly intravascular, leading to chronic anemia. Intravascular hemolysis is responsible for severe inflammation and endothelial dysfunction.

Maintaining hemoglobin in its oxygenated R-conformation is one of the strategies for inhibiting the polymerization of HbS. Previous experimental therapeutic approaches having this effect have been discontinued due to poor pharmaceutical properties or toxicity. Nevertheless, they proved the validity of the concept by demonstrating an increase in oxyhemoglobin and a decrease in biomarkers of hemolysis.

Voxelotor binds to the α chain of globin and maintains Hb in its R conformation, thereby inhibiting the polymerization of HbS while increasing the affinity of Hb for oxygen.

Because of its mechanism of action affecting anemia and hemolysis, Voxelotor is a promising treatment for the prevention and treatment of renal and cerebral arterial disease.

Hypothesis/Objective :

Investigator hypothesis is that the treatment by Voxelotor (GBT440) will improve intra vascular hemolysis and will increase the total mass of hemoglobin with beneficial effects on organ function.

The primary objective of the study is to evaluate the biological activity of Voxelotor on the reduction of intra vascular hemolysis measured by plasma hemoglobin.

The secondary objectives of the study will aim at characterizing the effects of GBT 440 Voxelotor on:

Intra vascular hemolysis measured by plasma Heme
Total hemoglobin mass (MHb)
RBCs lifespan
Blood volumes (plasma volume (PV), red blood cell mass (RBCM), total blood volume (BV))
Blood viscosity
Cerebral perfusion
Cerebrovascular vaso-reactivity
Cognitive function (MoCA)
Six minute walk test
Renal perfusion and iron deposits in renal cortex
Measurement of Glomerular filtration rate Estimation of glomerular filtration rate (CKD/EPI equation)
Urine albumin/creatinine ratio
Ability to decrease or stop erythropoietin in patients under EPO treatment
Safety (VOC, ACS, Priapism) and tolerability of voxelotor
RBC properties

Method:

This is an open-label, single-arm, single-stage phase II trial in patients treated with Voxelotor 1500 mg daily for 48 weeks. Assessments will be done during the study at week 0, week 6, week 12, week 24, week 36 and week 48.

ipd_sharing_description: APHP IS DATA'S OWNER, PLEASE CONTACT BOARD


title: Clinical Trial Data Set Re-use With Statistical Methodologies Tailored for Clinical Trials in Rare Diseases

acronym: EPISTOPIDEAL

summary:
Tuberous sclerosis complex (TSC), affecting 1 in 6.000 live births, is characterized by the development of multisystem tumors. Seizures are frequent up to 80% of individuals. They usually start in infancy and are often drug resistant, with a high risk of intellectual disability and autism spectrum disorders. In animal models, preventive treatment before seizures onset significantly decreased the risk of epilepsy as well as associated comorbidities.

EPISTOP randomized clinical trial (RCT) aimed to validate the effect of preventive therapy in patients with TSC diagnosed before clinical seizures with abnormal EEG, versus late standard therapy of epilepsy, administered after the seizures onset. This preventive therapy resulted in a significant better outcome in seizures and co-morbidities. However, this trial included few patients and did not allow to fully explore the secondary endpoints.

Our goal within EPISTOP-IDEAL project is to benefit from joining clinical expertise of EPISTOP project and experts from IDEAL EU project on methodologies for CTs in small populations in order to consolidate the results of EPISTOP CT using uncertainty evaluation of the existing data of randomized and observational arms and adding important information from external data collected after EPISTOP ended.

This collaboration aims to an optimal use of all available data (RCT, observational and external data collected with the same protocol). The goal is to demonstrate the added value of these methodologies in TSC CT and to their further use to rare epilepsies, and other rare diseases.

lead_sponsor: Imagine Institute


title: Sarcopenia Physical Activity and Metabolomic

acronym: SPAM

summary: Muscle failure (sarcopenia or dynapenia) is a factor of frailty and therefore, ultimately, of loss of autonomy in the elderly. Currently, no biomarker of muscle failure has a high sensitivity, specificity and positive predictive value. Several results, although preliminary, suggest that metabolomics could facilitate the early identification of frail patients, allowing the implementation of primary prevention strategies. Untargeted high-resolution metabolomics analysis would identify discriminative biomarkers and biological mechanisms associated with frailty. Finally, the hypothesis that metabolic signatures can be identified as risk factors for the development of age-related dynapenia should be tested in a longitudinal design.


title: Clinical Evaluation of Interstitial Laser Thermal Therapy Under Continuous MRI Monitoring as a Minimally Invasive Treatment of Patients With Medically Unbalanced Partial Epilepsy

acronym: EPILITT

summary: Laser Induced Interstitial Thermal Therapy (LITT) is a "minimally invasive" procedure that uses the heat generated by a laser light (65°) to destroy brain lesions by coagulation leading to lesion necrosis under real-time MRI monitoring. The laser optical fiber is implanted into the lesion using stereotaxy. This technique, which can be performed under local anesthesia and on an outpatient basis, proved its efficacy and safety in the treatment of brain metastases for the first time in the world in 2006 (A. Carpentier et al, 2008, 2011). Since then, more than 5,000 patients have been treated in the USA, including for epileptogenic lesions (FDA device and CE cleared). Our goal is to evaluate LITT on lesions with drug-resistant epilepsy for which surgical resection is impossible. No therapeutic trial evaluating LITT in this indication has been performed to date. It is therefore necessary to study its feasibility and tolerance.


title: Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis Collection

acronym: SNP

summary: Numerous neurological disorders affecting the central and peripheral nervous system can be attributed to the immune system through multiple effector mechanisms. However, current treatments could be drastically improved by faster and more accurate diagnosis. The sample collection will benefit to patients with rare neuroimmune syndromes such as Autoimmune Encephalitis (AE) and Paraneoplastic Neurological Syndromes (PNS) leading to a better and early diagnosis, as well as treatment improvement.

lead_sponsor: Hospices Civils de Lyon

location_facility: Centre de référence des syndromes neurologiques paranéoplasiques et encéphalites autoimmunes


title: Study MOTIF : mTOR Inhibitors: the Lesions Induced by Papillomavirus for Transplant Patients

acronym: MOTIF

summary:
The injuries induced by Human Papillomavirus (HPV) (anogenital condyloma mainly) are more frequent among transplanted patients due to their immunosuppression. These injuries are benign but they have a negative impact on the patients' quality of life. The initial treatment is topical and then surgical. The injuries can relapse, especially among transplanted patients.

The modification of the immunosuppressant treatment with a switch to mTOR inhibitors (mammalian Target Of Rapamycin) has shown its efficacy in preventing the recurrence of squamous cell carcinomas or treating Kaposi's disease.

By analogy, this therapeutic strategy can be sometimes put forward to transplanted patients with HPV-induced injuries.

The principal objective of this study is to describe the evolution of HPV-induced lesions in solid organ transplant patients.


title: Effect of Controlling Environmental Risk Factors in Established RA

acronym: DISRUPT-estRA

summary:
The factors contributing to the development of rheumatoid arthritis are multiple, with a role of the environment and a predisposing genetic background.
Among the modifiable environmental factors :unbalanced diet, overweight, low physical activity, smoking, periodontal disease, stress have been identified as risk factors for developing RA.
By causing low-grade inflammation and stimulation of the immune system (particularly through adipokines, citrullination phenomena and changes in the microbiota), these factors promote the onset of the disease and could also participate in the maintenance of inflammatory processes.
Thus, obese subjects have more active RA, a lower therapeutic response, and weight loss is associated with lower disease activity ; sedentary lifestyle is associated with more active RA and increased physical activity has beneficial effects on RA; people who smoke respond less well to treatment; periodontal disease is associated with more active RA and their treatment is associated with a decrease in this activity.
Finally, different methods having a beneficial impact on stress (mindfulness meditation, yoga, relaxation, etc.) have shown interesting results in patients with RA.
It is important to note that all of these factors are also associated with an increased cardiovascular risk, the leading cause of death in RA.
The combination of these factors probably has synergistic effects and it is therefore relevant to propose a correction of all these factors in the same program.
We have developed a management program for environmental risk factors for RA based with experts including rheumatologists, nutritionists, smoking cessation specialists, periodontal disease specialists and stress specialists.

location_facility: Centre Hospitalier Universitaire de Montpellier


title: Evolution of Sleep Quality During the Initiation of Continuous Positive Airway Pressure Treatment in Obstructive Sleep Apnea Syndrome: An Exploratory Study

summary:
Continuous positive airway pressure (CPAP) has a caricatural effect in reducing nocturnal respiratory abnormalities and improving the micro-and macrostructure of sleep. Studies characterizing the improvement of acute sleep parameters after the initiation of CPAP are limited to one or two nights of polysomnographic recording. This is related to the cost of performing these studies with repeated recordings in the laboratory and to the acceptability by patients to perform multiple nights of recordings.

Investigators currently have powerful and reliable methods allowing us to carry out nights at home in the patient's ecosystem, in real-life conditions. The characterization of sleep parameters by these methods is equivalent to a polysomnographic recording.

These technological innovations will allow us to characterize sleep before the initiation of CPAP treatment during several nights performed at home. Investigators will then be able to characterize the kinetics and stability of the improvement of sleep parameters in patients with obstructive sleep apnea syndrome in whom continuous positive airway pressure is initiated.

These data will be original and will serve as exploratory data to judge whether the objective improvement of sleep parameters in the first weeks of treatment is associated with improvement in sleepiness, quality of life, and compliance with treatment.


title: Interest of GLP1 Analogues (aGLP1) in Overweight Type 2 Diabetic Patients With Chronic Inflammatory Bowel Disease (IBD)

acronym: DiagMICI

summary:
The risk of type 2 diabetes appears to be higher in patients with chronic inflammatory diseases, including chronic inflammatory bowel disease (IBD). IBD is a group of inflammatory diseases that includes mainly Crohn's disease and ulcerative colitis.

Although the majority of IBD patients are not overweight, the prevalence of obesity in this population remains significant, estimated at 15 to 40%. It has been shown that obesity can impact the response to therapies used in IBD as well as the clinical course of the disease:

1) plasma concentrations of immunomodulatory therapies are often lower in the obese compared to those with a normal Body Mass Index (BMI) with a lower dose per kg of the administered drug as well as an acceleration of drug clearance.

2nd) Surgical management of IBD is associated with a higher risk of peri- and post-operative complications in obese patients, including an increase in operating time, bleeding risk, length of hospital stay and percentage of post-operative infections.

3e) Finally, obesity seems to have a negative impact on the clinical course of IBD, with a correlation between an increase in BMI and an increase in the number of hospitalizations, the number of follow-up consultations and the need for therapeutic escalation.

One of the common pathophysiological explanations between IBD and metabolic syndrome (including type 2 diabetes and obesity), would involve metabolites in the gut that are modulated by the gut microbiota.

Glucagon-Like Peptide 1 (aGLP1) analogues are a new class of injectable antidiabetic drugs that have revolutionized the management of type 2 diabetes. They include exenatide, lixisenatide, liraglutide, dulaglutide and semaglutide. They combine an effect on glycemic control but also usually a weight loss. In some countries, they are used in non-diabetic obese patients, with a weight loss of up to -10 to -15%. These molecules bind to GLP1 receptors, stimulate insulin secretion when blood glucose levels are high, decrease glucagon secretion, slow gastric emptying and stimulate satiety. In addition to glycemic control, weight reduction is most often associated.

In addition, some aGLP1s have been shown to reduce cardiovascular events in diabetics. They are well tolerated, but their side effects are mainly digestive, such as nausea, vomiting and sometimes diarrhea. These problems occur in about 20% of cases, most often after the first injection, with vomiting requiring permanent cessation of treatment. Most often they gradually subside, spontaneously or after symptomatic treatment, and allow titration of the drug.

Due to the lack of studies and possible intestinal effects, aGLP1 is not recommended in cases of severe gastrointestinal disease, and therefore in cases of IBD, although it is not contraindicated.

The main objective of this study is to test the interest of these GLP1 analogues in type 2 diabetics with IBD, who are overweight and whose glycemic target is not reached. The expected benefit is to facilitate diabetes control and weight loss in this population. The second objective is to monitor the occurrence of adverse events in this population with the different GLP1 analogues used.

ReferenceCitation: Dregan A, Charlton J, Chowienczyk P, Gulliford MC. Chronic inflammatory disorders and risk of type 2 diabetes mellitus, coronary heart disease, and stroke: a population-based cohort study. Circulation. 2014 Sep 2;130(10):837-44. doi: 10.1161/CIRCULATIONAHA.114.009990. Epub 2014 Jun 26.

ReferenceCitation: Jess T, Jensen BW, Andersson M, Villumsen M, Allin KH. Inflammatory Bowel Diseases Increase Risk of Type 2 Diabetes in a Nationwide Cohort Study. Clin Gastroenterol Hepatol. 2020 Apr;18(4):881-888.e1. doi: 10.1016/j.cgh.2019.07.052. Epub 2019 Aug 5.

ReferenceCitation: Singh S, Dulai PS, Zarrinpar A, Ramamoorthy S, Sandborn WJ. Obesity in IBD: epidemiology, pathogenesis, disease course and treatment outcomes. Nat Rev Gastroenterol Hepatol. 2017 Feb;14(2):110-121. doi: 10.1038/nrgastro.2016.181. Epub 2016 Nov 30. Review.

ReferenceCitation: Seminerio JL, Koutroubakis IE, Ramos-Rivers C, Hashash JG, Dudekula A, Regueiro M, Baidoo L, Barrie A, Swoger J, Schwartz M, Weyant K, Dunn MA, Binion DG. Impact of Obesity on the Management and Clinical Course of Patients with Inflammatory Bowel Disease. Inflamm Bowel Dis. 2015 Dec;21(12):2857-63. doi: 10.1097/MIB.0000000000000560.

ReferenceCitation: Hicks G, Abdulaal A, Slesser AAP, Mohsen Y. Outcomes of inflammatory bowel disease surgery in obese versus non-obese patients: a meta-analysis. Tech Coloproctol. 2019 Oct;23(10):947-955. doi: 10.1007/s10151-019-02080-0. Epub 2019 Sep 17.

ReferenceCitation: Pavelock N, Masood U, Minchenberg S, Heisig D. Effects of obesity on the course of inflammatory bowel disease. Proc (Bayl Univ Med Cent). 2019 Feb 1;32(1):14-17. doi: 10.1080/08998280.2018.1542887. eCollection 2019 Jan.

ReferenceCitation: Verdugo-Meza A, Ye J, Dadlani H, Ghosh S, Gibson DL. Connecting the Dots Between Inflammatory Bowel Disease and Metabolic Syndrome: A Focus on Gut-Derived Metabolites. Nutrients. 2020 May 15;12(5). pii: E1434. doi: 10.3390/nu12051434. Review.

ReferenceCitation: Nauck M, Frid A, Hermansen K, Shah NS, Tankova T, Mitha IH, Zdravkovic M, Düring M, Matthews DR; LEAD-2 Study Group. Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes Care. 2009 Jan;32(1):84-90. doi: 10.2337/dc08-1355. Epub 2008 Oct 17.

ReferenceCitation: O'Neil PM, Birkenfeld AL, McGowan B, Mosenzon O, Pedersen SD, Wharton S, Carson CG, Jepsen CH, Kabisch M, Wilding JPH. Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial. Lancet. 2018 Aug 25;392(10148):637-649. doi: 10.1016/S0140-6736(18)31773-2. Epub 2018 Aug 16.

ReferenceCitation: Astrup A, Rössner S, Van Gaal L, Rissanen A, Niskanen L, Al Hakim M, Madsen J, Rasmussen MF, Lean ME; NN8022-1807 Study Group. Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study. Lancet. 2009 Nov 7;374(9701):1606-16. doi: 10.1016/S0140-6736(09)61375-1. Epub 2009 Oct 23. Erratum in: Lancet. 2010 Mar 20;375(9719):984.

ReferenceCitation: Zatorski H, Sałaga M, Fichna J. Role of glucagon-like peptides in inflammatory bowel diseases-current knowledge and future perspectives. Naunyn Schmiedebergs Arch Pharmacol. 2019 Nov;392(11):1321-1330. doi: 10.1007/s00210-019-01698-z. Epub 2019 Jul 29. Review.


title: Usual Care Intervention Research Evaluating the Impact of a Personalized Pharmaceutical Plan on the Duration of Opioid Treatment in Non-cancerous Pain

acronym: PPP-Care

summary:
Many treatments with WHO grade III opioids are being introduced in the rheumatology department for non-cancerous pain. The duration of this treatment prescribed at discharge is often uncontrolled and sometimes leads to significant addiction.

The team at the local pain center recommends an average duration of 28 days for this type of pain. There is a full-time pharmacy intern in the rheumatology department.

The aim of this work is to evaluate the impact of a targeted pharmaceutical interview on the duration of the morphine treatment initiated during hospitalization.

lead_sponsor: University Hospital, Rouen