title: Creation of a Normal Database for FluoroDeoxyGlucose-Positron Emission Tomography (FDG-PET) Neurological Examinations: Study of Principal Inter-individual Variation Factors

acronym: BDD TEP FDG

summary: The purpose of this study is to define a reference population for FDG-PET neurological examinations starting from patients having FDG-PET to supervise a non-complicated lymphoma (tumor in remission, low disabling chronic tumor).

location_facility: Service de Médecine Nucléaire, Hôpital Central


title: Evaluation of Neuropsychological Effects of Drug-resistant Anterior Temporal Epilepsy and Anterior Temporal Lobectomy in Face Perception

acronym: ATENA-F

summary:
The purpose is to evaluate neuropsychological effects of anterior temporal epilepsy in face perception by comparison of performances of epileptic patients and control individuals, sex-, age- and socio-educational level-matched.

Secondary purposes are to prospectively evaluate neuropsychological impact of anterior temporal lobectomy performed for surgical treatment of anterior temporal epilepsy on face perception (exploratory study).

study_start_date_type: Actual

status: Unknown status

study_completion_date_type: Anticipated

study_type: Interventional

design_allocation: Non-Randomized

primary_purpose: Other

enrollment_type: Anticipated

ipd_sharing: No

lead_sponsor: Central Hospital, Nancy, France

location_facility: Service de Neurologie, Hôpital Central, CHU de Nancy

intervention_type: Other

lead_sponsor_type: academique

status_simplified: Unknown


title: Endoprosthesis Treatment Effects on Human Abdominal Aorta Aneurysms(AAA)Metabolic Activity

acronym: AAAendo

summary: The purpose of this study is to determine whether Positron Emission Tomography imaging can help to predict the evolutivity of AAA treated with endovascular prosthesis.

status: Completed

primary_purpose: Diagnostic

enrollment_type: Actual

location_facility:
Brabois Hospital
Institut du Thorax, Nantes's Hospital
Bichat Claude Bernard Hospital
Cardiologic Hospital
Le Bocage - Dijon's Hospital
Georges Pompidou European Hospital
CH.NICOLLE's Hospital

intervention_type: Radiation

status_simplified: Completed


title: Development of New Prenatal Diagnostic Tests From Maternal Blood

summary: After extraction of the cell-free DNA circulating in maternal plasma, we aim at developing new techniques for fetal DNA enrichment to perform fetal gender determination, and indirect diagnosis of inherited diseases like Cystic Fibrosis, Huntington Disease, Myotonic Dystrophy, B-Thalassaemia...

status: Terminated

lead_sponsor: University Hospital, Strasbourg, France

intervention_type: Genetic


title: Role and Interactions of Adenosine, Receptors, Methionine Cycle Nutritional, Metabolic and Genetic Determinants in the Onset of Atrial Fibrillation in Normal Heart

acronym: FACS

summary:
The purpose of this study is to analyze the association of atrial fibrillation onset in normal heart and:

Genetic determinants (genes of receptors, enzymes involved in synthesis and degradation, genes of bioavailability of coenzymes and nutritional precursors)
Metabolic determinants of adenosine and methionine cycles
Nutritional determinants.

Secondary purposes are:

Analysis of physiopathologic mechanisms of AF in normal hearts and adenosine metabolisms and its interaction with methionine metabolism, according to identified genetic determinants
Analysis of blood markers of adenosine and methionine metabolites as phenotypic markers of detected polymorphisms
Evaluate the role of adenosine receptors in AF onset

primary_purpose: Basic Science

location_facility: Département de Cardiologie, CHU Nancy, Hôpitaux de Brabois

intervention_type: Biological


status: Recruiting

primary_purpose: Treatment

acronym: TREOCAPA

intervention_type: Drug

title: Prophylactic Treatment of the Ductus Arteriosus in Preterm Infants by Acetaminophen

lead_sponsor: Institut National de la Santé Et de la Recherche Médicale, France

type: EudraCT Number

source: euctr

design_allocation: Randomized

location_country: Denmark Portugal Ireland Estonia Finland Switzerland Hungary France Belgium Norway Sweden

location_facility: Kuopio University Hospital, Department of Pediatrics

location_facility: Hôpital Arnaud de Villeneuve, Département de Pédiatrie Néonatale et Réanimation Pédiatrique

location_facility: Centre Hospitalier Universitaire de Liège

location_facility: Oulu University Hospital, Department of Pediatrics

location_facility: Hopital Universitaire de Geneve (HUG) - Hopital des enfants

location_facility: CENTRE hospitalier intercommunal de Creteil

location_facility: Hopital Cochin, Service de Médecine et Réanimation néonatales de Port-Royal

location_facility: The Juliane Marie Centre, Rigshospitalet, Copenhagen University hospital

location_facility: Tartu University Hospital, Neonatal and Paediatric Intensive Care Unit

location_facility: Helsinki University Hospital, Department of Children and Adolecents, Neonatology

location_facility: Centro Hospitalar Universitário Lisboa Norte, EPE -Hospital Santa Maria

location_facility: Turku University Hospital, Department of Peadiatrics

location_facility: Hospice civils de Lyon, Hopital Femme Enfant

location_facility: Tampere University Hospital, Department of Pediatrics

location_facility: Centro Hospitalar e Universitário do Porto, EPE - Centro Materno Infantil do Norte

summary:
TREOCAPA is a Phase II/III European Multicentre study concerning the prophylactic treatment by Acetaminophen of extremely preterm infant during the first five days after birth.

The Phase II is a dose finding phase in order to assess the minimum effective dose regimen of acetaminophen for the closure of PDA for neonates with a gestational age less than 27 weeks This part of the study will be conducted in 11 NICUs, in 4 countries (France, UK, Finland and Denmark).

The Phase III is The phase III is a randomized, multicenter, double-blind, placebo-controlled superiority trial, two arms in a 1:1 ratio, evaluating an increasing of 10% of the percentage of survival without severe morbidity at 36 weeks of post menstrual age. In the intervention arm, 20 mg/kg followed by 7.5 mg/kg quarter in die (QID) will be administered to the 27-28 weeks gestational age group (dosage confirmed through PK/PD data analysis from the previous Finnian study) and the dosage selected after the conclusion of the Phase II will be administered to the 23-26 weeks gestational age group. A group sequential design, with a total of 3 analyses (2 interim analyses and a final) and the O'Brien-Fleming alpha spending function is chosen for the trial. At the same time, a Bayesian sequential analysis is planned for safety endpoints

status_simplified: Ongoing


title: Impact of Using the Oncogramme® Device to Select the First Line of Treatment (Chemotherapies +/- Targeted Therapies) for Patients With Metastatic Colorectal Cancer on Progression-free Survival, Treatment Costs, Efficiency and Quality of Life Compared to Usual Patient Care.

summary:
Colorectal cancer is the 2nd leading cause of cancer death in France. Its incidence is nearly 45,000 new cases per year in 2017, with an estimated 5-year survival of 63% in 2015. Metastases are seen in 40-60% of colorectal cancer cases. The 5-year survival rate ranges from 5% to 15% for patients with widespread metastatic disease.

Two types of treatments are used to treat colon cancer: surgery and medication protocol (chemotherapeutic drugs and targeted therapies). These treatments can be used alone or in combination.

The current choice of a first line of chemotherapy is left to the practitioner's discretion, after consultation with a multidisciplinary consultation meeting. The choice of treatment(s) depends on official recommendations and is based on the results of clinical trials conducted on large populations, and takes into account the toxicities of the therapies used and the general condition of the patients. The therapeutic combinations for colorectal cancers are therefore multiple. However, to date, no consensus has been reached to ensure that each patient is treated effectively and as a unique case.

Today, functional sensitivity tests offer the possibility for patients to be offered a personalized treatment against cancer. This is the case of the Oncogramme® device developed by Oncomedics, which is the first functional sensitivity test dedicated to oncology in Europe. It is based on an in vitro analysis of each patient's tumor cells in order to compare the responses of the tumor cells to the different molecules and therapeutic combinations available (chemotherapy ± targeted therapy). This response, translated into a tumor-specific sensitivity profile, can be used by the medical team to determine the most appropriate treatment for the patient. This test is therefore likely to improve the benefit-risk ratio of a chemotherapy treatment in colorectal cancer by allowing the medical team to select, among the treatments deemed effective, the one that will be the most effective on the tumor and possibly with the least side effects.

The hypothesis of this study is that the personalization of treatments (by chemotherapy associated or not with targeted therapies) proposed by the Oncogramme®-colorectal device would allow to promote the best possible clinical response, to limit the side effects and ultimately to improve the survival and the quality of life of the patient.

study_start_date_type: Anticipated

status: Not yet recruiting

lead_sponsor: Oncomedics

intervention_type: Diagnostic Test

lead_sponsor_type: industriel


title: Evaluation of the Immune Response After Vaccination Against Hepatitis B in Patients With Indolent Lymphoproliferative Disorders With no Treatment.

acronym: EVACC-B

summary: The purpose of this study is to assess the seroconversion rate and the cellular immune response after vaccination against hepatitis B virus in patients with lymphoproliferative syndrome like chronic lymphocytic leukemia stade A and follicular lymphoma without of treatment criteria.

primary_purpose: Prevention


title: Hémorragies et Maladie Veineuse Thromboembolique du Post-partum : Epidémiologie, Etudes Des déterminants Cliniques et Biologiques

acronym: HEMOTHEPP

summary: The aim of this study is to evaluate the frequencey and the determinants of postpartum major complications (hemorrhage and thrombosis) up to 3 months after delivery in the maternity hospitals of Finistère (Bretagne - France)

study_type: Observational

time_perspective: Prospective

lead_sponsor: University Hospital, Brest

location_facility: CHRU de Brest - Service de Gynécologie-obstétrique


title: Artificial Intelligence Use for the Detection of Atrial Fibrillation Drivers

acronym: AI Fib

summary: pilot clinical study, multicenter, prospective, open, nonrandomized

status: Withdrawn

study_completion_date_type: Actual

lead_sponsor: Hospital St. Joseph, Marseille, France

location_country: Netherlands France

location_facility:
Isala Hospital
CHU Nice
Hopital d'Aix en Provence


title: Early Intensification of Combination Antiretroviral Therapy Including FUZEON® in the Treatment of Progressive Multifocal Leucoencephalopathy During HIV-1 Infection ANRS 125 Trial

summary:
Progressive multifocal leucoencephalopathy (PML) is a rare infectious disease of the brain, provoked by the JC virus. It usually occurs in subjects with impaired immune system as during HIV infection. To date, there is no specific antiviral treatment susceptible to cure PML. But it was shown in the setting of HIV-related PML, that combination antiretroviral therapy allows a restoration of the immune system and then might stop the progression of PML.

The objective of this study is to appreciate the supplementary efficiency brought by an association of more powerful antiretroviral molecules including enfuvirtide on the evolution of PML. This research program will involve 30 patients in several centres in France. All the patients who will participate will receive enfuvirtide during 6 months in association with a combination of two or more potent antiretroviral drugs. The total duration of follow-up for a patient will be of 1 year.

ReferenceType: derived

ReferenceCitation: Gasnault J, Costagliola D, Hendel-Chavez H, Dulioust A, Pakianather S, Mazet AA, de Goer de Herve MG, Lancar R, Lascaux AS, Porte L, Delfraissy JF, Taoufik Y; ANRS 125 Trial Team. Improved survival of HIV-1-infected patients with progressive multifocal leukoencephalopathy receiving early 5-drug combination antiretroviral therapy. PLoS One. 2011;6(6):e20967. doi: 10.1371/journal.pone.0020967. Epub 2011 Jun 30.

lead_sponsor: French National Agency for Research on AIDS and Viral Hepatitis

location_facility: Service de Medecine interne et Maladies Infectieuses, Hopital Bicetre


title: Safety and Clinical Performance of a Non-cross-linked Porcine Acellular Dermal Matrix Used in Dental Surgery

summary:
The general objective of the study is to confirm the medium/long-term safety and clinical performance of the CELLIS Dental membrane used in dental surgery and to identify emerging risks in comparison to clinical data related to other treatment modalities.

The present study will be a prospective multicentric non-randomized and noncontrolled trial involving 50 patients followed for 24 months. The study will be conducted in France in 4 investigational centres.

lead_sponsor: Meccellis Biotech

location_facility:
Cabinet PISB
Cabinet dentaire Grange Blanche
Cabinet dentaire Saint Priest en Jarez
Cabinet dentaire des chênes

intervention_type: Device


title: Comparison of Two Neuromuscular Transmission Monitors Based on Acceleromyography: TOF-Watch SX® and TOFScan®

acronym: TOFScan

summary:
The purpose is to evaluate the reproducibility of neuromuscular monitoring data of recovery from neuromuscular blockade, obtained with TOFScan® and TOF-Watch SX®, in adult and pediatric population.

Secondary purposes are to evaluate the reproducibility of data obtained with 2 monitors for:

the onset of clinical action of curare: suppression of the first response of train of four monitoring (T1) of 95% initial value
the duration of clinical action of curare: recovery of the first response of train of four monitoring (T1) to 25% initial value
recovery of first (T1), second (T2), third (T3) and fourth response (T4) of train of four monitoring, and recovery of T4/T1 to 40% and 60% initial value (T4/T1 0.4 and 0.6)
complete recovery from curarisation, at T4/T1=90% and T4/T1=100%.

location_facility: CHRU de NANCY - Hôpitaux de Brabois - Département d'Anesthésie-Réanimation


title: Influence of Social Determinants of Health on the Management of Hepatocellular Carcinoma in the French National Cohort Study CHIEF

acronym: SOCIAL-CHIEF

summary:
With 8,000 related deaths per year, HCC is one of the most dangerous cancers in France. The main reason for the poor prognosis of HCC is most often a diagnosis at an advanced stage ineligible for curative treatment. In the field of oncology, low participation to screening is closely linked to socioeconomic status (e.g. level of education, income, employment). In HCC, the socioeconomic status is linked to incidence, overall survival and treatment allocation in US, UK and Australia. This suggests that the social environment should be taken into account when designing interventions and policies that allows facilitating the medical pathways for patients with HCC with the ultimate goal of improving the overall prognosis. However, the studies assessing the impact of social determinants on the management of HCC in France are limited. Bryère at al. reported that the highest incidence and the worst prognosis of HCC were observed in the most disadvantaged populations in France. To date, there is no available data concerning the influence of social determinants on: implementation of surveillance programs of HCC, stage of disease at the time of diagnosis or treatment allocation. This data is essential for better understanding the geographic disparities observed in France and for developing the strategies to remedy them.

CHIEF is a multicenter longitudinal observational study of patients with HCC (ClinicalTrials.gov Identifier: NCT04348838), that will collect the exhaustive data including patient and tumor characteristics, diagnostic circumstances and modalities, care pathway from diagnostic imaging to referral to expert center, treatment allocation and implementation, and 5-year follow up including recurrent assessment of quality of life.

Social-CHIEF is an ancillary study to the CHIEF cohort (approved by CHIEF scientific committee). The population of this study will consist in a subset of patients from the CHIEF prospectively included or already recruited who accept to participate in this study. The data collected in CHIEF will be retrieved from the CHIEF main database and additional data about social determinants will be specifically investigated by self-administrated questionnaires. The results obtained will provide a better understanding of the influence of social determinants on health trajectories of HCC patients. These data will be essential in recommending new health policies and in designing innovative intervention studies to address social disparities.

time_perspective: Other

ReferenceType: background

ReferenceCitation: Costentin CE, Mourad A, Lahmek P, Causse X, Pariente A, Hagège H, Dobrin AS, Becker C, Marks B, Bader R, Condat B, Héluwaert F, Seitz JF, Lesgourgues B, Denis J, Deuffic-Burban S, Rosa I, Decaens T; CHANGH Study Group. Hepatocellular carcinoma is diagnosed at a later stage in alcoholic patients: Results of a prospective, nationwide study. Cancer. 2018 May 1;124(9):1964-1972. doi: 10.1002/cncr.31215. Epub 2018 Mar 28.

ReferenceCitation: Damiani G, Basso D, Acampora A, Bianchi CB, Silvestrini G, Frisicale EM, Sassi F, Ricciardi W. The impact of level of education on adherence to breast and cervical cancer screening: Evidence from a systematic review and meta-analysis. Prev Med. 2015 Dec;81:281-9. doi: 10.1016/j.ypmed.2015.09.011. Epub 2015 Sep 25. Review.

ReferenceCitation: Herbert C, Launoy G, Gignoux M. Factors affecting compliance with colorectal cancer screening in France: differences between intention to participate and actual participation. Eur J Cancer Prev. 1997 Feb;6(1):44-52.

ReferenceCitation: Jembere N, Campitelli MA, Sherman M, Feld JJ, Lou W, Peacock S, Yoshida E, Krahn MD, Earle C, Thein HH. Influence of socioeconomic status on survival of hepatocellular carcinoma in the Ontario population; a population-based study, 1990-2009. PLoS One. 2012;7(7):e40917. doi: 10.1371/journal.pone.0040917. Epub 2012 Jul 13.

ReferenceCitation: Singal AG, Li X, Tiro J, Kandunoori P, Adams-Huet B, Nehra MS, Yopp A. Racial, social, and clinical determinants of hepatocellular carcinoma surveillance. Am J Med. 2015 Jan;128(1):90.e1-7. doi: 10.1016/j.amjmed.2014.07.027. Epub 2014 Aug 10.

ReferenceCitation: Clark PJ, Stuart KA, Leggett BA, Crawford DH, Boyd P, Fawcett J, Whiteman DC, Baade PD. Remoteness, race and social disadvantage: disparities in hepatocellular carcinoma incidence and survival in Queensland, Australia. Liver Int. 2015 Dec;35(12):2584-94. doi: 10.1111/liv.12853. Epub 2015 May 22.

ReferenceCitation: Bryere J, Dejardin O, Bouvier V, Colonna M, Guizard AV, Troussard X, Pornet C, Galateau-Salle F, Bara S, Launay L, Guittet L, Launoy G. Socioeconomic environment and cancer incidence: a French population-based study in Normandy. BMC Cancer. 2014 Feb 13;14:87. doi: 10.1186/1471-2407-14-87.

ReferenceCitation: Tron L, Belot A, Fauvernier M, Remontet L, Bossard N, Launay L, Bryere J, Monnereau A, Dejardin O, Launoy G; French Network of Cancer Registries (FRANCIM). Socioeconomic environment and disparities in cancer survival for 19 solid tumor sites: An analysis of the French Network of Cancer Registries (FRANCIM) data. Int J Cancer. 2019 Mar 15;144(6):1262-1274. doi: 10.1002/ijc.31951. Epub 2018 Dec 3.

lead_sponsor: University Hospital, Grenoble


title: Observational Study of the Impact of the COronaVirus Disease 2019 (COVID-19) Epidemic on Patients With Myeloproliferative Neoplasias

acronym: COVIM

summary: The classic myeloproliferative neoplasias (MNP), including polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF) or secondary to PV or ET, are among the most frequent of malignant hemopathies, with overall prevalence estimated at around 10,000 patients followed in France. Due to the median age of patients around 65, the frequency of cardiovascular complications of these thrombogenic diseases and the impact of cytoreductive treatments on immune cells, these patients are considered to be at risk of developing forms severe of COVID-19. This study will assess the impact of MNPs on the risk of developing a severe form of COVID-19, identify new risk factors linked to the disease as well as the impact of treatments for MNPs according to their pharmacological class.

time_perspective: Retrospective

lead_sponsor: French Innovative Leukemia Organisation


type: Registry Identifier

title: Design Of WELL Being Monitoring Systems, Application in Autism

acronym: Do Well B

summary: The worldwide prevalence of autism is constantly increasing. People with autisms have difficulties in communication and social interaction resulting from atypical perceptual and information processing, leading to the accumulation of anxiety. Extreme overloading experienced internally may not be visible externally. Identifying stressful situations at an early stage may avoid socially problematic behavior from occurring, such as self-injurious behavior. Activation of the autonomous nervous system (ANS) is involved in the response to anxiety, which can be measured through heart rate variability and skin conductance with the use of a portable device, non-intrusively and pain-free. Thus, developing innovative analysis of signal perception and reaction is necessary, mainly for the non-communicative individuals with autism.

ReferenceCitation: Dutheil F, Chambres P, Hufnagel C, Auxiette C, Chausse P, Ghozi R, Paugam G, Boudet G, Khalfa N, Naughton G, Chamoux A, Mermillod M, Bertrand PR. 'Do Well B.': Design Of WELL Being monitoring systems. A study protocol for the application in autism. BMJ Open. 2015 Feb 20;5(2):e007716. doi: 10.1136/bmjopen-2015-007716.

lead_sponsor: University Hospital, Clermont-Ferrand

location_facility: University Hospital of Clermont-Ferrand (CHU), France

intervention_type: Behavioral


title: Cognitive Sequels of Cushing Syndrome

acronym: MEMOCUSH

summary: Cushing's disease is a state of chronic endogenous glucocorticoid excess. Cushing's disease is responsible for increased morbidity and mortality. Recent studies have pinpointed the frequency of somatic sequelas and persistent alteration in quality of life despite the cure of the disease. More specifically, a few studies have described persistent psychopathology, maladaptive personality and cognitive impairments in patients with a history of Cushing's disease. Among these, hippocampal memory deficits have been found in the majority of studies, a finding that is consistent with the alterations described in hippocampal neurons during chronic exposure to glucocorticoids. However, the tools currently available to assess hippocampal-dependent memory are multiple, sometimes difficult to perform by clinicians and to analyze or may lack of diagnostic sensitivity. The investigators have recently developed an original tool, the virtual radial task in 3D, which has shown to be reliable to detect subtle alterations in hippocampal-dependent memory in several human diseases. The primary aim of the study is the evaluation of persistent cognitive impairments (hippocampal memory) in patients cured of Cushing's disease for at least one year using the virtual radial task in 3D and to compare it with that obtained with classical cognitive tests.

ReferenceCitation: Pupier E, Santos A, Etchamendy N, Lavielle A, Ferriere A, Marighetto A, Resmini E, Cota D, Webb SM, Tabarin A. Impaired quality of life, but not cognition, is linked to a history of chronic hypercortisolism in patients with Cushing's disease in remission. Front Endocrinol (Lausanne). 2022 Aug 8;13:934347. doi: 10.3389/fendo.2022.934347. eCollection 2022.


type: Other Identifier

title: Monitoring of JOB STRESS Related to Night Shifts in OPHthalmology Physicians and Residents

acronym: JOBSTRESS-OPH

summary:
Ophthalmology physicians and residents work under stress conditions during night emergency ophthalmology shifts. Under time pressure, that is a characteristic of the urgency of care, they must use all their cognitive resources to make an accurate diagnosis and to provide accurate decisions, with sometimes surgical emergency acts. In addition, in France, they work at night following by an usual day work, and they can also work 48 consecutive hours during weekends, followed by a work day … i.e. 60 consecutive hours of work … Long working hours with a short recovery time has been demonstrated to be a major factor of stress and fatigue. Even if not demonstrated on ophthalmologists, those working conditions may contribute to symptoms of mental exhaustion and physical fatigue (sleep deprivation), often accompanied by a loss of motivation at work. This may leads to a feeling of loss of time control; stress can also distort the perception of time and leads to hasty actions or delayed decision-making. The combined effects of stress, feelings of loss of time control, and fatigue necessarily have an impact on work performance and work quality, with a high risk of medical error. Moreover, prolonged stress may expose ophthalmologists to a higher risk of multiple diseases, predominantly systemic inflammation and coronary heart disease.

The main hypothesis is that prolonged work (up to 60 consecutive working hours) may impact on HRV, comparatively to a typical working day.

primary_purpose: Screening


title: Physical Activity Experiment on Male Prostate Cancer Patients : Feasibility Multicenter Study of an Innovative Follow-up by Peers

summary: Prostate cancer is the most common cancer in France (56,841 cases in 2012). Although the benefits of physical activity (PA) in cancer patients are currently well established in the scientific literature, several studies have shown that this population is not sufficiently active. Strengthen patient adherence to prevention counseling by the physical activity (PA) is emerging as a new challenge for personalized treatment in oncology. In order to encourage the engagement and maintenance in a regular PA of cancer patients, first, their experiences of physical activity (PA) practice should be considered and their initial social representations of the practice considered. Secondarily, it is also important to identify health professionals who retain a key role in defining the framework, objectives and means of action to promote lifestyle changes towards a more active lifestyle. In addition, peer mentoring appears to offer promising perspectives for promoting adherence and long-term maintenance in physical activity (PA) of cancer patients.

primary_purpose: Supportive Care

lead_sponsor: Centre Hospitalier Universitaire de Saint Etienne

location_facility:
ICLN - Oncologie médicale
ICLN - département de radiothérapie
CHU Saint-Etienne


title: Elderly CAncer Patient: Qualitative and Quantitative Factors of Inclusion Failure in Clinical Trials

acronym: Quali-SAGE

summary:
The transposition of the results of biomedical research to medical management of patients in real-life setting depends highly from patient's selection. In Europe and the United States, the majority of cancers occur after 65 years. In France, 45% of cancers diagnosed in 2012 were after 70 years or 158,722 in absolute value. In this context, the median age at diagnosis was 72 years old. Disease particularly affecting the elderly, cancer is also characterized by the importance of biomedical research devoted to it. Despite the dynamism of the research activity in oncology and therefore the number of affected patients, the elderly are paradoxically sparsely included in clinical trials. Numerous studies have focused in recent years, to identify possible causes of under-representation of elderly patients in clinical trials but most of them focused on eligibility criteria and few on barriers related to non-invitation or non-inclusion in eligible patients.

The investigator postulate that a qualitative survey based on an structured epidemiological device will able to objective evidences of reasons related to the patient, participant familial caregivers, participant physician and the clinical center organization for participating or not to a clinical trial and the interrelations between the identified reasons.

The main objective is to assess reasons of non-participation of older patients with cancer in clinical trials, from the physicians, patients and family caregivers' perspectives using qualitative and quantitative methods.

The secondary objectives are:

To investigate the social representation and construction of being "aged" from the patient, physician and family caregiver perspective (qualitative part).

To compare the reasons of non-participation regarding age class (old and very old), localized versus metastatic disease and tumor site (quantitative part).

To characterize the profiles of participants and non-participants to clinical trial among older patients with cancer thanks to qualitative and quantitative data.

Method Quali SAGE is a French, socio-epidemiologic, multicenter prospective study that includes patients aged 70 years or over, with solid tumor (irrespective of the stage) in French hospitals.

lead_sponsor: Assistance Publique - Hôpitaux de Paris


title: A Pilot Study to Evaluate the Safety of a 3 Weeks Sitagliptin Treatment in HCC Patients Undergoing Liver Resection

acronym: HCC-DPPIV

summary: Boosting of tumor cell killing by cytotoxic lymphocytes may be a promising means to enhance anti-tumor immunity. Prior studies demonstrated that tumor infiltration by cytotoxic lymphocytes correlates with control of tumor growth and is associated with an improved prognosis in cancer patients. Trafficking of activated lymphocytes is a tightly regulated mechanism and the specific nature of the chemokine milieu is a crucial determinant for permitting T cell entry into the tumor microenvironment. CXCL10 is an interferon-inducible chemokine particularly important for the recruitment of activated T, and it has been shown to enhance anti-tumor responses through its action on cytotoxic T cells (e.g., glioblastoma, colorectal adenocarcinoma and lung carcinoma). Additionally, roles for CXCL10 as an anti-tumor effector include its ability to chemo-attract NK cells into sites of inflammation, and its ability to inhibit development of new vasculature and induce the regression of newly formed vessels. Adding a layer of complexity, the function of CXCL10 can be regulated by dipeptidylpeptidase IV (DPPIV), leading to the formation of a dominant negative, antagonist form of the chemokine. This was initially demonstrated in vitro, and recent work has provided convincing in vivo evidence that antagonist forms of CXCL10 regulate lymphocyte trafficking. The main goal of this protocol is to evaluate the tolerance of sitagliptin treatment in HCC patients, and secondary DPPIV inhibitors as a strategy for protecting CXCL10 chemokine agonist activity as a means to enhance tumor regression.


title: Effects of Stabilization Shoes on Balance and Walking. A Cross-over, Controlled, Randomized Single Blind Study.

acronym: BALAGE

summary:
Movement during everyday activities most often requires stable posture. Postural control corresponds to a complex motor ability to maintain / re-establish balance and orient one's body in the environment. Postural stability and equilibrium deteriorate with age. More than 30% of people over 65 years old fall per year. Falls represent 90% of hip fractures and sometimes result in lasting psychological effects. Shoes are our direct link between the ground and our feet. Wearing shoes plays a major role in postural control. The characteristics of shoes usually worn by elderly people are identified with those of shoes known to be 'dangerous'. In order to improve stability and reduce the risk of falling for the elderly, Axis-Comfort Development® has developed "experimental balance shoes". Their shoes have technical characteristics presented in the scientific literature as beneficial for postural stability.

Therefore, the aim of this study was to investigate the effects of wearing experimental balance shoes on postural balance compared with the people's own shoes. We assumed that postural balance would be improved by experimental balance shoes in an acute way and improved by a familiarization phase.

This was a controlled, randomized, blind and cross-over study. three sessions were held in our center, each time interspersed with a phase of familiarization at home (7 to 10 days) during which the people had to wear either the experimental balance shoes or their own personal shoes. 21 volunteers in total participated in this study, all between 65 and 75 years old. Five tests were presented randomly for each session and all tests were carried out on a Huber 360 ® (LPG System, France) stabilometric platform. The mains criteria were static equilibrium on one foot and two feet (with eyes open and closed) and secondary criteria were stride frequency during the walk on the spot and stability limits.

An improvement of these multiple criteria during the different sessions would be proof of the positive effect of experimental balance shoes on postural balance in the elderly.

lead_sponsor: University of Burgundy

location_facility: Centre d'Expertise de la Performance - Université de Bourgogne


title: Developing Derived Induced Pluripotent Stem Cells From Blood as a Model for the Study to Understand Imprinted Disorders

acronym: ID-STEM

summary:
Fetal and postnatal growth is finely regulated by genetic, epigenetic and environmental mechanisms. Parental imprinting is a regulatory mechanism that allows monoallelic expression of certain genes from a single parental allele through differential DNA methylation. Imprinted genes play a very important role in the control of fetal and postnatal growth. The pathophysiological mechanisms of these epimutations are largely unknown.

Studying the consequences of these epimutations on the molecular signature of the imprinted gene network in these patients would provide a better understanding of the epigenetic mechanisms regulating fetal growth. As these genes are weakly expressed in fibroblasts, these studies will be carried out on pluripotent stem cells or IPSCs (Induced Pluripotent Stem Cells).

status: Enrolling by invitation

ipd_sharing: Yes

ipd_sharing_description: IPD will be sahred with partners

lead_sponsor: Institute of Cardiometabolism and Nutrition, France


title: Efficacy of Intact Cord Resuscitation Compared to Immediate Cord Clamping on Cardiorespiratory Adaptation at Birth in Infants With Isolated Congenital Diaphragmatic Hernia (CDH)

acronym: CHIC

summary:
Isolated CDH is a rare disease (1/3500) and displays a wide range of severity and outcome. Despite attempts to standardize the management of this disease at birth and during the first months of life, the mortality varies from 20 to 50% according to different hospitals in France and abroad.

Several studies already showed the benefice of late cord clamping at birth on biological and physiological adaptation of newborns to life. Previous works also suggest a possible benefit of this procedure for babies with CDH.

This multicenter randomized clinical study aims to investigate the efficacy of intact cord resuscitation compared to immediate cord clamping on cardiorespiratory adaptation at birth in full term newborn infants with isolated CDH.

lead_sponsor: University Hospital, Lille

location_facility:
Chu de Nantes -
Hop Jeanne de Flandre Chu Lille
Chu Amiens Picardie

intervention_type: Procedure


title: French National Registry of Rare Peritoneal Surface Malignancies (RENAPE Registry)

acronym: RENAPE

summary:
Despite advances in the management of and changes in clinical practice, little is known about the epidemiology, patterns of care and outcomes of rare peritoneal surface malignancies patients in France.

In order to better understand the characteristics of rare peritoneal surface malignancies and to evaluate treatment strategies, the RENAPE registry aims at the collection of data from patients presenting with a rare peritoneal surface malignancy in France. Data will be entered prospectively in a specifically designed and secured web database.

All RENAPE's centres and physicians are invited to register patients with a rare peritoneal surface malignancy diagnosis and to participate to the registry. Data will be evaluated within regular time frames, focusing on types of rare peritoneal surface malignancies, treatment modalities and patient outcomes (e.g. survival, recurrence), thereby contributing to the better understanding of these rare cancers.

ReferenceCitation: Villeneuve L, Passot G, Glehen O, Isaac S, Bibeau F, Rousset P, Gilly FN; RENAPE Network. The RENAPE observational registry: rationale and framework of the rare peritoneal tumors French patient registry. Orphanet J Rare Dis. 2017 Feb 17;12(1):37. doi: 10.1186/s13023-017-0571-y.

lead_sponsor: Hospices Civils de Lyon

location_facility: Institut Cancérologie de l'Ouest - René Gauducheau

location_facility: Institut de Cancérologie de l'Ouest - Paul Papin

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


title: Development of Medication Reconciliation Using Electronic Pharmaceutical Record: a National Multicenter, Cluster-randomized, Two-period Crossover Study in Elderly Hospitalized in Geriatrics, Internal Medicine and Orthopedic Surgery

acronym: CONCIPAGE

summary:
Context Adverse drug events (ADEs) may occur in hospitalized patients and may result from discrepancies between patient's current medications and the drugs prescribed at admission (omission,, dosing errors….).

Consequences of these discrepancies may be mild (e.g. isolated biological abnormalities), but may also lead to severe clinical outcomes. Medication reconciliation is a process of creating the most accurate list of patient's current medication in order to decrease discrepancies and eventually ADEs.

Information technology and electronic health records are of great interest in this process. In France, medications dispensed in community pharmacies during the past 4 months are registered in a patient's electronic pharmaceutical record. The impact of this record, together with pharmacist medication reconciliation, will be tested in the CONCIPAGE study.

Design The CONCIPAGE study is a national, multicenter, cluster-randomized, two-period cross-over study. It will estimate the impact of medication reconciliation, made by a pharmacist, using the patient pharmaceutical record, on the occurrence of ADEs during the hospitalization of patients aged 65 years and over.

primary_purpose: Health Services Research


title: Retrospective Study of Singing-voice Disorders and Aerodynamic Profiles in Dysodic Singers

acronym: AeroDysodiaPro

summary:
Singers are over-represented in phoniatric consultation; they present increased risk of developing voice disorders. They represent a specific population among phoniatric patients (specific singing-voice complaints, increased sensitivity to voice). Singing-voice disorder is called dysodia in the same way as dysphonia, which refers to speaking-voice disorders. The diagnosis of dysodia is made after a laryngeal examination and a voice assessment to identify patient's speech and singing difficulties. Most studies on prevalence of voice disorders in singers come from the American continent. Very few descriptions of this population have been made in France.

Voice assessment of dysodic singers includes aerodynamic voice measurements. The use of aerodynamic measurements for the diagnosis of voice pathologies is now widely demonstrated. These parameters include measurements of estimated subglottal pressure (ESGP), phonation threshold pressure (PTP) (minimum pressure to initiate a sound) and oral airflow (OAF). They depend on the level of training of singers and the type of vocal dysfunction. Aerodynamic behaviours of dysodic singers have not yet been described, although they can help to better identify the singer's vocal difficulties and could be essential parameters for targeting more precisely rehabilitation exercises proposed in voice therapy.

This study aims to describe the characteristics of a French population of singers consulting in phoniatrics and their aerodynamic behaviours. Do the singers' aerodynamic parameters (pressure, flow) reflect the dysfunctions in singing voice? Based on results of the literature on speaking and singing non-pathological voice, the investigators hypothesize that during voice assessment, ESGP values will be increased and OAF ones will be decreased over the entire vocal range of the singer in case of voice pathology.

status: Active, not recruiting

ipd_sharing: Undecided

ipd_sharing_description: NC

lead_sponsor: University Hospital, Montpellier


title: Multicenter Study to Explore the Impact of Florbetaben (FBB) in Change of Diagnosis in Patients Who Are Evaluated for AD and in Whom Lumbar Puncture is Contraindicated or CSF Results Are Ambiguous

lead_sponsor: Piramal Imaging Limited

ReferenceCitation: Ceccaldi M, Jonveaux T, Verger A, Krolak-Salmon P, Houzard C, Godefroy O, Shields T, Perrotin A, Gismondi R, Bullich S, Jovalekic A, Raffa N, Pasquier F, Semah F, Dubois B, Habert MO, Wallon D, Chastan M, Payoux P; NEUUS in AD study group, Stephens A, Guedj E. Added value of (18)F-florbetaben amyloid PET in the diagnostic workup of most complex patients with dementia in France: A naturalistic study. Alzheimers Dement. 2018 Mar;14(3):293-305. doi: 10.1016/j.jalz.2017.09.009. Epub 2017 Nov 4.

location_facility: Coordinating center (Hôpital de La Timone) and 18 associated centers in France

summary:
This phase 4 study will explore, in the context of the present French clinical practice, the impact of florbetaben 18F (FBB) in patients evaluated for AD who require a biomarker for etiologic determination of the cognitive and functional impairment, but in whom:

lumbar puncture was not feasible for medical conditions
results of cerebrospinal fluid (CSF) analysis were considered ambiguous by treating physicians
lumbar puncture (LP) was refused by the patient


title: PALUREA: Severe Falciparum Imported Malaria in Adults: Clinical and Physiopathological Study

acronym: PALUREA

summary:
Plasmodium falciparum malaria remains a major public health problem in endemic areas, with approximately 2 million deaths each year, especially in tropical African countries.

In non-endemic industrialized areas, imported malaria is generally diagnosed in travelers, as well as immigrants from endemic countries. Such imported cases have increased worldwide, with approximately 7000 cases each year in France. Among these cases, 300 are severe requiring hospitalization in the intensive care unit (ICU) with an overall mortality rate of 10%, despite available effective care.

Many studies have been performed to evaluate clinical and physiopathological aspects of severe malaria in endemic areas but few data are available for imported malaria. Therefore, determinants of severe imported malaria are not well known. The majority of patients hospitalized in the ICU for severe malaria are white caucasians as well as those patients who die.

The present study has two main objectives:

(i) to describe the clinical spectrum of severe imported malaria and to assess outcome (mortality and neurological sequelae), and the biological interactions between host and the parasite,

(ii) to evaluate the role of gene polymorphisms, of parasitic factors in the occurrence of severe malaria with a case control study comparing severe and non-severe malaria in patients matched according to ethnic patterns. The intensity of the inflammatory response will also be studied in the two groups of patients.

ReferenceType: result

ReferenceCitation: Bruneel F, Hocqueloux L, Alberti C, Wolff M, Chevret S, Bédos JP, Durand R, Le Bras J, Régnier B, Vachon F. The clinical spectrum of severe imported falciparum malaria in the intensive care unit: report of 188 cases in adults. Am J Respir Crit Care Med. 2003 Mar 1;167(5):684-9. Epub 2002 Oct 31.


title: Effectiveness and Cost Of ICD Follow-up Schedule With Telecardiology

acronym: ECOST

summary: In many aspects of every-day life, modern communication systems bring about a remarkable increase in comfort and safety by transmitting data and information in an easy and reliable manner. In order to provide these advantages also to patients with implantable cardioverter-defibrillators, as well as to their physicians, BIOTRONIK has developed a long-distance implant telemetry to enable periodic trend and event-triggered transmissions of implant data and intracardiac electrogram over distances of several meters. The data is received by a patient device and subsequently automatically transferred to a BIOTRONIK Service Center that provides it to the physician on a password secured internet site. Hence, the physician receives diagnostic information without the patient having to visit the physician (Home Monitoring, HM). New possibilities will arise for a detailed medical and event-correlated supervision of the patient's therapy using electrically active implants.

ReferenceCitation: Guédon-Moreau L, Lacroix D, Sadoul N, Clémenty J, Kouakam C, Hermida JS, Aliot E, Kacet S; ECOST trial Investigators. Costs of remote monitoring vs. ambulatory follow-ups of implanted cardioverter defibrillators in the randomized ECOST study. Europace. 2014 Aug;16(8):1181-8. doi: 10.1093/europace/euu012. Epub 2014 Mar 9.

ReferenceCitation: Guédon-Moreau L, Kouakam C, Klug D, Marquié C, Brigadeau F, Boulé S, Blangy H, Lacroix D, Clémenty J, Sadoul N, Kacet S. Decreased delivery of inappropriate shocks achieved by remote monitoring of ICD: a substudy of the ECOST trial. J Cardiovasc Electrophysiol. 2014 Jul;25(7):763-70. doi: 10.1111/jce.12405. Epub 2014 Apr 10.

ReferenceCitation: Guédon-Moreau L, Lacroix D, Sadoul N, Clémenty J, Kouakam C, Hermida JS, Aliot E, Boursier M, Bizeau O, Kacet S; ECOST trial Investigators. A randomized study of remote follow-up of implantable cardioverter defibrillators: safety and efficacy report of the ECOST trial. Eur Heart J. 2013 Feb;34(8):605-14. doi: 10.1093/eurheartj/ehs425. Epub 2012 Dec 13.

lead_sponsor: Biotronik SE & Co. KG


title: Detection of Plasma DNA by Allelotyping in Non Small Cell and Small Cell Lung Cancer Patients. Evolution During Treatment and Follow-up.

summary: The majority of lung cancer patients have a tumor-derived genetic alteration in circulating plasma DNA that could be exploited as a diagnostic tool. The aim of this study is to evaluate if plasma DNA can be used as a valuable non invasive test to monitor disease progression without assessing the tumor.

lead_sponsor: University Hospital, Strasbourg, France

location_facility: Service de Pneumologie, Hôpital de Hautepierre

location_facility: Service de Chirurgie Thoracique, Hôpital Civil


title: Seroprevalence of Chikungunya at the End of the First Chikungunya Outbreak in the French Antilles Within a Sample of Patients Treated for a HIV Infection

acronym: ChikVIH

summary:
Late 2013, the first indigenous cases of chikungunya have been observed in the French Antilles. At the end of May 2014, almost all of the islands of the Caribbean were affected by the outbreak.

During the large epidemic which affected the Island of La Réunion in 2005/2006, the attack rate was 38%. The most active period was three months.

In this context, knowledge of the attack rate and the epidemic in the Caribbean is an important issue for outbreak management and modeling work.

As the chikungunya virus had never circulated in the Caribbean, determining the seroconversion rate can be achieved by realizing a seroprevalence survey among the general population at the end of the outbreak. Another simple method is to estimate the rate in a cohort of patients followed regularly and whose habitat is distributed throughout the territory studied.

The follow up of patients infected by the human immunodeficiency virus (HIV) in the French West Indies is almost exclusively performed in hospitals in department of Infectious and Tropical Diseases.The high prevalence of HIV and homogeneous distribution of infected patients on all of our territories, allow to hypothesize that the risk of transmission of arboviruses by exposure to mosquito bites is comparable to the general population. This patient cohort is well suited to study the emergence of Chikungunya in the French West Indie .

Primary objective :

To estimate the cumulative incidence at the end of the first Chikungunya outbreak in the French West Indies by estimating the prevalence of specific antibodies of chikungunya virus in a sample (randomly constituted) from patients infected by HIV and representative of the general population of Martinique and Guadeloupe

Secondary objective :

To estimate the frequency of asymptomatic infections by the chikungunya virus in the studied population To estimate the frequency of chronic forms of chikungunya in the studied population

ReferenceCitation: Pialoux G, Gaüzère BA, Jauréguiberry S, Strobel M. Chikungunya, an epidemic arbovirosis. Lancet Infect Dis. 2007 May;7(5):319-27. Review.

ReferenceCitation: Farnon EC, Sejvar JJ, Staples JE. Severe disease manifestations associated with acute chikungunya virus infection. Crit Care Med. 2008 Sep;36(9):2682-3. doi: 10.1097/CCM.0b013e3181843d94.

ReferenceCitation: Brouard C, Bernillon P, Quatresous I, Pillonel J, Assal A, De Valk H, Desenclos JC; workgroup "Quantitative Estimation of the Risk of Blood Donation Contamination by Infectious Agents". Estimated risk of Chikungunya viremic blood donation during an epidemic on Reunion Island in the Indian Ocean, 2005 to 2007. Transfusion. 2008 Jul;48(7):1333-41. doi: 10.1111/j.1537-2995.2008.01646.x. Epub 2008 Feb 22.

ReferenceCitation: Liumbruno GM, Calteri D, Petropulacos K, Mattivi A, Po C, Macini P, Tomasini I, Zucchelli P, Silvestri AR, Sambri V, Pupella S, Catalano L, Piccinini V, Calizzani G, Grazzini G. The Chikungunya epidemic in Italy and its repercussion on the blood system. Blood Transfus. 2008 Oct;6(4):199-210.

ReferenceCitation: Sissoko D, Moendandze A, Malvy D, Giry C, Ezzedine K, Solet JL, Pierre V. Seroprevalence and risk factors of chikungunya virus infection in Mayotte, Indian Ocean, 2005-2006: a population-based survey. PLoS One. 2008 Aug 26;3(8):e3066. doi: 10.1371/journal.pone.0003066.

ReferenceCitation: Appassakij H, Khuntikij P, Kemapunmanus M, Wutthanarungsan R, Silpapojakul K. Viremic profiles in asymptomatic and symptomatic chikungunya fever: a blood transfusion threat? Transfusion. 2013 Oct;53(10 Pt 2):2567-74. doi: 10.1111/j.1537-2995.2012.03960.x. Epub 2012 Nov 26.

ReferenceCitation: Bianco C. Dengue and Chikungunya viruses in blood donations: risks to the blood supply? Transfusion. 2008 Jul;48(7):1279-81. doi: 10.1111/j.1537-2995.2008.01806.x.

ReferenceCitation: Ramful D, Carbonnier M, Pasquet M, Bouhmani B, Ghazouani J, Noormahomed T, Beullier G, Attali T, Samperiz S, Fourmaintraux A, Alessandri JL. Mother-to-child transmission of Chikungunya virus infection. Pediatr Infect Dis J. 2007 Sep;26(9):811-5.

ReferenceCitation: Gérardin P, Barau G, Michault A, Bintner M, Randrianaivo H, Choker G, Lenglet Y, Touret Y, Bouveret A, Grivard P, Le Roux K, Blanc S, Schuffenecker I, Couderc T, Arenzana-Seisdedos F, Lecuit M, Robillard PY. Multidisciplinary prospective study of mother-to-child chikungunya virus infections on the island of La Réunion. PLoS Med. 2008 Mar 18;5(3):e60. doi: 10.1371/journal.pmed.0050060.

ReferenceCitation: Gérardin P, Guernier V, Perrau J, Fianu A, Le Roux K, Grivard P, Michault A, de Lamballerie X, Flahault A, Favier F. Estimating Chikungunya prevalence in La Réunion Island outbreak by serosurveys: two methods for two critical times of the epidemic. BMC Infect Dis. 2008 Jul 28;8:99. doi: 10.1186/1471-2334-8-99.

ReferenceCitation: Van Bortel W, Dorleans F, Rosine J, Blateau A, Rousset D, Matheus S, Leparc-Goffart I, Flusin O, Prat C, Cesaire R, Najioullah F, Ardillon V, Balleydier E, Carvalho L, Lemaître A, Noel H, Servas V, Six C, Zurbaran M, Leon L, Guinard A, van den Kerkhof J, Henry M, Fanoy E, Braks M, Reimerink J, Swaan C, Georges R, Brooks L, Freedman J, Sudre B, Zeller H. Chikungunya outbreak in the Caribbean region, December 2013 to March 2014, and the significance for Europe. Euro Surveill. 2014 Apr 3;19(13). pii: 20759. Erratum in: Euro Surveill. 2014;19(14):pii/20764. Rousset, D [added].

ReferenceCitation: Curlier E, Fagour L, Herrmann-Storck C, Staelen A, Vingadassalom I, Breurec S, Abel S, Pierre-François S, Jean-Marie J, Laouénan C, Césaire R, Hoen B, Cabié A. Seroprevalence of chikungunya virus infection among HIV-infected adults in French Caribbean Islands of Martinique and Guadeloupe in 2015: A cross-sectional study. PLoS Negl Trop Dis. 2021 Apr 9;15(4):e0009267. doi: 10.1371/journal.pntd.0009267. eCollection 2021 Apr.

lead_sponsor: University Hospital Center of Martinique

location_facility: Centre Hospitalier Universitaire de Fort-de-France


title: Development of a Fast Measurement Technique of Insulin Resistance in Human, With 123-6-deoxy-6 Iodo-D-glucose, a New Tracer of Glucose Transport

acronym: GLUCIMAG

summary:
Insulin resistance, characterised by a depressed cellular sensitivity to insulin in insulin-sensitive organs, is a central feature of the metabolic syndrome. In people with no diabetes mellitus, the presence of metabolic syndrome leads to an increase of mortality, whatever the cause, but, as a majority, cardiovascular diseases.

In patients with type 2 diabetes mellitus, the presence of a metabolic syndrome leads to an increase in major adverse cardiovascular events. The prevalence of metabolic syndrome is led to grow in a near future, because of the increase of diabetes mellitus and obesity prevalence.

Actually, there is no simple tool to measure insulin resistance. The gold standard technique remains the hyperinsulinemic euglycemic clamp. However, the complexity and length of this technique render it unsuitable for routine clinical use. Many methods or index have been proposed to assess insulin resistance in human, but none have shown enough relevance to be used in clinical use.

Within the investigators U877 INSERM team, the investigators previously performed in vivo biodistribution studies with 6-DIG (6-deoxy-6-iodo-D-glucose), a new tracer of glucose transport, radiolabelled with123 iodine, with and without insulin, on the one hand in genetically diabetic mice (db/db), consequently having a severe insulin resistance and in the other hand in rats with acquired insulin resistance after a "fructose diet".

The investigators have demonstrated that 6-DIG is able to identify in vivo slight glucose transport variations in insulin sensible organs. Then, the investigators developed a fast and simple imaging protocol with a small animal gamma camera, which allows the obtaining of an insulin resistance index for each organ, directly transferable to human.

The investigators project is to transfer to human this measurement technique, perfectly validated in animal.

The main goal of this monocentric phase I-II study is to evaluate the tolerance to the insulin resistance measurement technique with 6DIG scintigraphy, in healthy volunteers and in diabetic patients. The investigators plan to enrol 6 healthy volunteers and 6 type 2 diabetic patients.

The investigators secondary goals will be to evaluate feasibility and reproducibility of the measurement technique, to follow pharmacokinetic and to assess efficacy of 6-DIG to measure insulin resistance.

lead_sponsor: Institut National de la Santé Et de la Recherche Médicale, France

location_facility: Service de Biophysique et Médecine Nucléaire, CHU de Grenoble


title: Rôle de la Microarchitecture Osseuse Dans le déterminisme héréditaire de la fragilité Osseuse

acronym: MODAM

summary: The aim of this study is to analyze the hereditary determinism of bone microarchitecture measured at the distal radius and distal tibia from a case control-study of mother-daughter pairs.

time_perspective: Cross-Sectional

location_facility: Unité Inserm 831, Pavillon F, Hôpital Edouard Herriot


title: Innovative Applications of Ultrafast Ultrasound Imaging in Peripheral Vascular Pathology: Evaluation of Carotid Plaque Vulnerability by Quantification of Neovascularization

acronym: ULTRA-VASC

summary:
Stroke is the second leading cause of death in the Western world and the leading cause of major lifelong disability. About 15% of strokes are secondary to thrombosis or embolization of an unstable atheromatous carotid plaque. In these symptomatic patients, the degree of carotid stenosis is correlated with the risk of early recurrence. Patients with stenosis over 70% are therefore offered an endarterectomy, an operation to remove carotid plaque, to prevent future strokes[1]. In asymptomatic patients, the degree of stenosis is a limited predictor, and better risk stratification is required to assess the degree of plaque vulnerability and stroke risk of the patient. The therapeutic decision towards endarterectomy in addition to drug therapy is debated because of a variable and dependent benefit/risk balance for each patient. A number of imaging parameters have been studied: ulceration, heterogeneity, vascularization of the plaque for example, but their place is not well defined [2].

The usual evaluation of carotid stenosis is by conventional Doppler ultrasound with calculation of the degree of stenosis according to the NASCET criteria.

For symptomatic stenoses the intervention is recommended when above 70% and is discussed from 50% to 70% of NASCET stenosis degree.

For asymptomatic stenoses, the procedure is discussed when above 60% taking into account the patient's life expectancy, the risk of the surgery and the unstable nature of the plaque [2].

Destabilization of the carotid plaque is partially induced by inflammation associated with neo-vascularization. The detection of these new vessels by conventional contrast ultrasound has already shown a distinction between stable and unstable plaques, by the presence or absence of microbubbles in the plaque. However, this assessment is not very precise and only the most vascularized plaques can be detected. Ultrafast ultrasound Imaging is a new ultrasonic Imaging modality that allows detecting low speed flows, a tiny vascular structure within the vessel wall.

RESEARCH HYPOTHESIS Plaques neo-vascularization would be more precisely detected and characterized by ultrafast imaging coupled with microbubble injection than conventional ultrasound imaging.

A better assessment of plaque instability could improve the selection of patients for carotid endarterectomy and increase the benefit/risk ratio of this preventive surgery.

ipd_sharing_description: Individual participant data (IPD) that underlie results in publication could be shared


title: The Clinical and Medico-economical Evaluation of Meniscal Allografts in the Sequelae of Total or Sub-total Meniscectomy.

acronym: ERAM

summary: Total or subtotal meniscectomies in young patients are currently responsible of pain and limitation of activities. There isn't any other treatment than meniscal replacement. But there is no randomized clinical trial on meniscal allograft to validate the efficiency of this treatment.

location_facility: POTEL Jean-François, Clinique Medipole Garonne

location_facility: Hôpital Avicenne - Service de Chirurgie orthopédique


title: Transcranial Magnetic Stimulation-based Assessment of Mental Training Effects on Motor Learning in Healthy Participants

acronym: IMAP-TMS

summary: The general purpose of this research project is to analyze the specific role of motor imagery on motor learning, assessed through corticospinal excitability measurements and behavioral data collection. This project is based on four sequences. For Sequence 1, the main objective is to examine the effect of mental training on movement speed and accuracy in a manual motor sequence task, as well as the influence of sensory feedback in immediate post-test (i.e., execution of a similar, but not identical, manual motor sequence, other manual tasks) on performance in delayed post-test. The secondary objective will be to examine corticospinal changes (i.e., amplitude of motor evoked potentials) induced by mental training, by measuring the amplitude of motor evoked potentials before and after mental training. For Sequence 2, the main objective is to examine the impact of a motor disturbance induced by a robotic arm at different intervals during the motor imagery process. The secondary objective will be to examine the corticospinal changes (i.e. amplitude of evoked motor potentials) induced by mental training as a function of the applied perturbations, before and after perturbation. For Sequence 3, the main objective will be to examine the influence of neuroplasticity on the quality of mental training. More specifically, the investigators will study the links between brain plasticity and motor learning through mental training. The secondary objective will be to examine the corticospinal changes (i.e. amplitude of evoked motor potentials) induced by mental training at different levels of the neuromuscular system (cortical, cervicomedullar, peripheral) after a training period. For Sequence 4, the main objective will be to examine the effect of short-term arm-immobilization of on the retention of motor learning induced by mental training. The secondary objective will be to examine the corticospinal changes (i.e., amplitude of motor evoked potentials) induced by of short-term arm-immobilization, or by transcranial direct current stimulation (tDCS), on motor learning. The results of this fundamental research project will allow a better understanding of neurophysiological and behavioral mechanisms that underlie motor learning through motor imagery. The results will allow to efficiently consider inter-individual specificities and will thus open up to clinical research perspectives, towards the establishment of adapted motor rehabilitation protocols.

ReferenceCitation: Abraham WC. Metaplasticity: tuning synapses and networks for plasticity. Nat Rev Neurosci. 2008 May;9(5):387. doi: 10.1038/nrn2356. Review.

ReferenceCitation: Anwar MN, Khan SH. Trial-by-trial adaptation of movements during mental practice under force field. Comput Math Methods Med. 2013;2013:109497. doi: 10.1155/2013/109497. Epub 2013 May 7.

ReferenceCitation: Allami N, Paulignan Y, Brovelli A, Boussaoud D. Visuo-motor learning with combination of different rates of motor imagery and physical practice. Exp Brain Res. 2008 Jan;184(1):105-13. Epub 2007 Sep 12.

ReferenceCitation: Arora S, Aggarwal R, Sevdalis N, Moran A, Sirimanna P, Kneebone R, Darzi A. Development and validation of mental practice as a training strategy for laparoscopic surgery. Surg Endosc. 2010 Jan;24(1):179-87. doi: 10.1007/s00464-009-0624-y. Epub 2009 Jul 25.

ReferenceCitation: Avanzino L, Giannini A, Tacchino A, Pelosin E, Ruggeri P, Bove M. Motor imagery influences the execution of repetitive finger opposition movements. Neurosci Lett. 2009 Nov 27;466(1):11-5. doi: 10.1016/j.neulet.2009.09.036. Epub 2009 Sep 20.

ReferenceCitation: Bienenstock EL, Cooper LN, Munro PW. Theory for the development of neuron selectivity: orientation specificity and binocular interaction in visual cortex. J Neurosci. 1982 Jan;2(1):32-48.

ReferenceCitation: Burianová H, Marstaller L, Sowman P, Tesan G, Rich AN, Williams M, Savage G, Johnson BW. Multimodal functional imaging of motor imagery using a novel paradigm. Neuroimage. 2013 May 1;71:50-8. doi: 10.1016/j.neuroimage.2013.01.001. Epub 2013 Jan 12.

ReferenceCitation: Cantarero G, Tang B, O'Malley R, Salas R, Celnik P. Motor learning interference is proportional to occlusion of LTP-like plasticity. J Neurosci. 2013 Mar 13;33(11):4634-41. doi: 10.1523/JNEUROSCI.4706-12.2013.

ReferenceCitation: Classen J, Liepert J, Wise SP, Hallett M, Cohen LG. Rapid plasticity of human cortical movement representation induced by practice. J Neurophysiol. 1998 Feb;79(2):1117-23.

ReferenceCitation: Cumming J, Hall C. Deliberate imagery practice: the development of imagery skills in competitive athletes. J Sports Sci. 2002 Feb;20(2):137-45.

ReferenceCitation: Decety J. The neurophysiological basis of motor imagery. Behav Brain Res. 1996 May;77(1-2):45-52. Review.

ReferenceCitation: Doyon J, Bellec P, Amsel R, Penhune V, Monchi O, Carrier J, Lehéricy S, Benali H. Contributions of the basal ganglia and functionally related brain structures to motor learning. Behav Brain Res. 2009 Apr 12;199(1):61-75. doi: 10.1016/j.bbr.2008.11.012. Epub 2008 Nov 17. Review.

ReferenceCitation: Doyon J, Benali H. Reorganization and plasticity in the adult brain during learning of motor skills. Curr Opin Neurobiol. 2005 Apr;15(2):161-7. Review.

ReferenceCitation: Gentili R, Han CE, Schweighofer N, Papaxanthis C. Motor learning without doing: trial-by-trial improvement in motor performance during mental training. J Neurophysiol. 2010 Aug;104(2):774-83. doi: 10.1152/jn.00257.2010. Epub 2010 Jun 10.

ReferenceCitation: Gentili R, Papaxanthis C, Pozzo T. Improvement and generalization of arm motor performance through motor imagery practice. Neuroscience. 2006 Feb;137(3):761-72. Epub 2005 Dec 9.

ReferenceCitation: Grush R. The emulation theory of representation: motor control, imagery, and perception. Behav Brain Sci. 2004 Jun;27(3):377-96; discussion 396-442.

ReferenceCitation: Guillot A, Moschberger K, Collet C. Coupling movement with imagery as a new perspective for motor imagery practice. Behav Brain Funct. 2013 Feb 20;9:8. doi: 10.1186/1744-9081-9-8.

ReferenceCitation: Halsband U, Lange RK. Motor learning in man: a review of functional and clinical studies. J Physiol Paris. 2006 Jun;99(4-6):414-24. Epub 2006 May 26. Review.

ReferenceCitation: Izawa J, Shadmehr R. Learning from sensory and reward prediction errors during motor adaptation. PLoS Comput Biol. 2011 Mar;7(3):e1002012. doi: 10.1371/journal.pcbi.1002012. Epub 2011 Mar 10.

ReferenceCitation: Jeannerod M. Neural simulation of action: a unifying mechanism for motor cognition. Neuroimage. 2001 Jul;14(1 Pt 2):S103-9. Review.

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ReferenceCitation: Keller PE. Mental imagery in music performance: underlying mechanisms and potential benefits. Ann N Y Acad Sci. 2012 Apr;1252:206-13. doi: 10.1111/j.1749-6632.2011.06439.x. Review.

ReferenceCitation: Lebon F, Lotze M, Stinear CM, Byblow WD. Task-dependent interaction between parietal and contralateral primary motor cortex during explicit versus implicit motor imagery. PLoS One. 2012;7(5):e37850. doi: 10.1371/journal.pone.0037850. Epub 2012 May 31.

ReferenceCitation: Lehéricy S, Benali H, Van de Moortele PF, Pélégrini-Issac M, Waechter T, Ugurbil K, Doyon J. Distinct basal ganglia territories are engaged in early and advanced motor sequence learning. Proc Natl Acad Sci U S A. 2005 Aug 30;102(35):12566-71. Epub 2005 Aug 17.

ReferenceCitation: Malouin F, Jackson PL, Richards CL. Towards the integration of mental practice in rehabilitation programs. A critical review. Front Hum Neurosci. 2013 Sep 19;7:576. doi: 10.3389/fnhum.2013.00576. Review.

ReferenceCitation: Minkova L, Peter J, Abdulkadir A, Schumacher LV, Kaller CP, Nissen C, Klöppel S, Lahr J. Determinants of Inter-Individual Variability in Corticomotor Excitability Induced by Paired Associative Stimulation. Front Neurosci. 2019 Aug 14;13:841. doi: 10.3389/fnins.2019.00841. eCollection 2019.

ReferenceCitation: Mulder T. Motor imagery and action observation: cognitive tools for rehabilitation. J Neural Transm (Vienna). 2007;114(10):1265-78. Epub 2007 Jun 20. Review.

ReferenceCitation: Opie GM, Evans A, Ridding MC, Semmler JG. Short-term immobilization influences use-dependent cortical plasticity and fine motor performance. Neuroscience. 2016 Aug 25;330:247-56. doi: 10.1016/j.neuroscience.2016.06.002. Epub 2016 Jun 6.

ReferenceCitation: Palmiero M, Belardinelli MO, Nardo D, Sestieri C, Di Matteo R, D'Ausilio A, Romani GL. Mental imagery generation in different modalities activates sensory-motor areas. Cogn Process. 2009 Sep;10 Suppl 2:S268-71. doi: 10.1007/s10339-009-0324-5.

ReferenceCitation: Rozand V, Lebon F, Stapley PJ, Papaxanthis C, Lepers R. A prolonged motor imagery session alter imagined and actual movement durations: Potential implications for neurorehabilitation. Behav Brain Res. 2016 Jan 15;297:67-75. doi: 10.1016/j.bbr.2015.09.036. Epub 2015 Sep 30.

ReferenceCitation: Rosenkranz K, Seibel J, Kacar A, Rothwell J. Sensorimotor deprivation induces interdependent changes in excitability and plasticity of the human hand motor cortex. J Neurosci. 2014 May 21;34(21):7375-82. doi: 10.1523/JNEUROSCI.5139-13.2014.

ReferenceCitation: Ruffino C, Papaxanthis C, Lebon F. The influence of imagery capacity in motor performance improvement. Exp Brain Res. 2017 Oct;235(10):3049-3057. doi: 10.1007/s00221-017-5039-8. Epub 2017 Jul 21.

ReferenceCitation: Saimpont A, Mercier C, Malouin F, Guillot A, Collet C, Doyon J, Jackson PL. Anodal transcranial direct current stimulation enhances the effects of motor imagery training in a finger tapping task. Eur J Neurosci. 2016 Jan;43(1):113-9. doi: 10.1111/ejn.13122. Epub 2015 Dec 15.

ReferenceCitation: Rulleau T, Robin N, Abou-Dest A, Chesnet D, Toussaint L. Does the Improvement of Position Sense Following Motor Imagery Practice Vary as a Function of Age and Time of Day? Exp Aging Res. 2018 Oct-Dec;44(5):443-454. doi: 10.1080/0361073X.2018.1521496. Epub 2018 Oct 9.

ReferenceCitation: Schuster C, Hilfiker R, Amft O, Scheidhauer A, Andrews B, Butler J, Kischka U, Ettlin T. Best practice for motor imagery: a systematic literature review on motor imagery training elements in five different disciplines. BMC Med. 2011 Jun 17;9:75. doi: 10.1186/1741-7015-9-75. Review.

location_facility: INSERM - U1093 Cognition, Action, and Sensorimotor Plasticity


title: Impact of Weight Loss on the Human Sperm Epitranscriptome

acronym: EPI-SPERM

summary:
Increasing evidence suggests that non-communicable diseases such as in particular obesity and its associated metabolic diseases are inherited from parents to children throughout several generations by epigenetic mechanisms. Thus, this environmental stress would induce epigenetic modification in the germ line that once transmitted and maintained in the progeny would induce the development of the parental pathologies. Considering the increasing prevalence of these pathologies worldwide, we urgently need to understand this process in human. Based on published and unpublished data demonstrating that sperm RNAs are vectors of epigenetic inheritance of obesity mouse model, the investigative team hypothesizes that epitranscriptome of obese men play a central role in the paternal epigenetic inheritance of obesity and its associated metabolic diseases as epigenetic vectors in this process.

To validate this hypothesis, the investigative team will use sperm from non-obese and obese men taken before and after surgery weight loss. Thanks to these cohorts, they propose to: (i) compare the epitranscriptome profiles of non-obese and obese men to identify the RNAs molecules which will be either qualitatively or quantitatively epigenetically modulated by obesity; (ii) compare the epitranscriptome profiles of obese men before and after surgery-weight loss to assess the reversibility of the newly acquired RNA modifications.

Giving some answers to this central question will provide not only some clues about the molecular mechanisms involved in this process, elements which might be crucial to stop the spread of this disorder, but will also allow the identification of obese-susceptibility loci which expression may be modulate by environmental factors and consequently able to transmit the disease.


title: Assessment of Apathy in a Real-life Situation, With a Video and Sensors-based System in Healthy Subject and Patient With Cerebral Disease

acronym: ECOCAPTURE

summary:
Apathy can be defined as a quantitative reduction of voluntary or goal-directed behavior.

So, the investigators propose a behavioral approach for assessing apathy, to obtain a quantifiable and objective signature of reduced goal-directed behavior by directly observing a patient in a real-life situation.

ECOCAPTURE consists of a multi-step scenario in a functional exploration platform equipped with data acquisition system based on video and sensors that track a participant's behavior.

The primary objective of this trial is to create a diagnostic tool for apathy, based on the video and sensors metrics.

A secondary objective of this trial is to validate a new experimental task (ICM_APATHY_TASKS) to test independently three main presumed mechanisms of apathy (motivation, cognitive inertia and coupling between motivation and action).

Another secondary objective aims to specify the pathophysiological mechanisms of apathy, corresponding to cognitive and behavioral processes, neural bases and neurohormonal mechanisms. The definition of pathophysiological mechanisms will allow the classification of apathetic patients (or several forms of apathy) and indicate which mechanism (s) best explains the apathy in a given patient.

location_facility: ICM / Pitié-Salpêtrière Hospital AP-HP / CIC


title: Decoding Presymptomatic White Matter Changes in Huntington Disease

acronym: Win-HD

summary:
WIN-HD is a monocentric longitudinal study comparing premanifest Huntingtin (HTT) mutation carriers and non HTT mutation carriers to determine that white-matter atrophy occurs far earlier than clinical onset in HD using Diffusion-weighted Nuclear Magnetic Resonance (N spectroscopy (DWS) and Diffusion Tensor Imaging (DTI).

The investigators will recruit up to 20 premanifest HTT mutation carriers (15 completed) and up to 20 non HTT mutation carriers (15 completed). It is important to have those 2 populations in order to compare our results and determine if there are significant white-matter changes far from the onset of HD. Therefore, non HTT mutation carriers will be age and gender matched to premanifest HTT mutation carriers.

In order to test the hypothesis, the study has 2 visits with a year interval.

This study is based on 4 principal criteria:

Imaging criteria
Clinical and neurological criteria
Psychological criteria
Behavioral criteria


title: Influence of TaqIB (rs708272) Polymorphism in Cholesteryl Ester Transfer Protein (CETP) Gene on Functionality of HDL Particles, in the Pathway of Reverse Transport of Fasting and Post-prandial Cholesterol.

acronym: HDL-PP

summary: Reverse cholesterol transport (RCT) pathway explains the anti-atherosclerosis role of HDL. Post prandial hypertriglyceridemia is highly predictive of atherosclerosis. TaqIB polymorphism in CETP gene plays a role on HDL particles, and might give a link between TaqIB polymorphism and the cardioprotective efficiency of HDL particles. Our main objective was to compare post-prandial HDL particles between patients having B2 allele carriers (genotype AA) to B1 allele carriers (genotype GG), and their ability to mediate cellular cholesterol efflux, via SR-BI Scavenger Receptor class B type I (SR-BI) , ABCG1 and ABCA1 pathways.

location_facility: Centre d'Investigation Clinique Paris Est


title: Effets du Tabagisme in Utero Sur la fonctionnalité de l'épithelium Respiratoire et Sur la Fonction Ventilatoire du Nouveau-né.

summary: Despite public campaigns to prevent cigarette smoking, it's about 20% of women who keep on smoking during pregnancy, exposing their fetus to prenatal tobacco adverse effects. Although environnemental tobacco smoke exposure effects are well known, consequences of prenatal tobacco smoke exposure (PTSE) need better caracterization. Previous animal study from our group have shown, in prenatal nicotine exposed mouse pups, alterations in tracheal epithelial structure similar to those observed in KO α7-nAChR mouse pups. These findings support the hypothesis that α7-nAChR are involved in the process of deleterious effects of tobacco smoking on respiratory epithelium development. The purpose of the present clinical study is to compare PTSE neonates with controls according to lung function and respiratory epithelial functionality. At the age of 3 days, small respiratory epithelium fragments will be obtained from gentle nasal brushing performed under antalgic premedication according to the method we previously published. Epithelium samples will be used for in vitro studies of α7-nAChR and CFTR functionality. Between the ages of 2 and 6 weeks, lung function testing will be performed, by means of baby-body plethysmography.


title: Emotional and Change-related Attention in Autism

acronym: AUTATTEN

summary: Several studies seem to indicate that emotional attention and change-related attention are impaired in ASD. The goal of this study is to identify the relationships between those two types of automatic attention in visual and auditory modalities in subjects with ASD compared to healthy controls and also, over the course of development (children, adults). In order to achieve this goal, the investigators will use complementary techniques (EEG and MRI-based techniques (fMRI, DTI)).


title: Relationship Between Endogenous CETP Activity and Atherosclerosis Distribution in Patients With High Cardiovascular Risk

acronym: CETP-ATHERO

summary:
The reverse cholesterol transport (RCT) pathway, which involves the centripetal movement of free cholesterol from peripheral tissues, including the vessel wall, to the liver represent the primary mechanism by which HDL protects against atherosclerosis and by which it may induce plaque regression. Recent data reveal that the capacity of HDL to efflux cholesterol from macrophages, a metric of HDL function reflecting the initial step of the RCT, is clinically relevant, displaying a strong inverse association with both carotid intima-media thickness and the severity of angiographic CAD; such observations were independent of HDL-C levels.

In human, the Cholesteryl Ester Transfer Protein (CETP), represents a key protein of the RCT pathway and mediates redistribution of neutral lipids between lipoproteins, has been identified as a potential therapeutic target against atherosclerosis. It is known that CETP activity correlates with HDL-C levels and represents a key modulator of the ability of whole plasma to mediate free cholesterol efflux from human macrophages.

Recent studies showed that 23% of endogenous plasma CETP activity variability is explained by plasma LDL-C (12.0%), HDL-C (6.4%) and TG (4.4%) whereas sex and BMI accounted together for only 0.7% of its variability. Scoring patients for cardiovascular risk on the basis of their plasma lipid levels (TC, TG, LDL-C and HDL-C), revealed that patients with high cardiovascular risk (score ≥3) displayed a mean endogenous plasma CETP activity above 34%. Therefore plasma CETP activity represents a potent indicator of cardiovascular risk in patients with metabolic disorders since it integrates major independent risk factors.

The objective of this study is to decipher the relationship between CETP, HDL efflux capacity and the development of atherosclerosis in humans in order to identify CETP as a potent biomarker of atherosclerosis distribution.


title: Contribution du Cervelet Dans l'Adaptation Sensori-motrice Via Les Oscillations Gamma : le Cas de la Dystonie

acronym: GAMMA

summary: Dystonia, a disabling disease with uncontrolled movement disorders was considered to be a manifestation of basal ganglia dysfunction, yet there is accumulating evidence from animal and human experiments that the cerebellum plays a prominent role in the pathophysiology of dystonia. Our recent results suggest a deficient cerebellar sensory encoding in dystonia, resulting in a decoupling of the motor component from the afferent information flow resulting from changes in the environment. An overall loss of gabaergic-mediated inhibition is at the forefront in dynamic changes in neural circuitry described in dystonia. In the mature brain gabaergic control the generation of temporal synchronies and oscillations in the glutamatergic neurons. Taken these all together with the results of a pilot experiment, the investigators hypothesize that deficient synchronies in the fast gamma range are one of the key mechanisms leading to abnormal communication inside the cerebello-cortical network in dystonia. The investigators aim first to demonstrate it by means of MEG (Magneto encepholography) recordings allowing to reconstruct the spatio-temporal dynamics of gamma oscillations in the nodes of the cerebello-cortical network. The investigators then aim to re-establish (if lost) or boost (if decreased) the defective synchronies by applying to the cerebellum at high gamma frequency a non invasive transcranial alternative current stimulation.


title: Obtention d'un modèle Cellulaire de la Maladie CADASIL à Partir de Fibroblastes cutanés de Patients

summary:
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucoencephalopathy (CADASIL) is an archetypal small vessel disease of the brain caused by dominant mutations in the NOTCH3 receptor. Cardinal vascular lesions include deposition of granular osmiophilic material (GOM) within the basal lamina of smooth muscle cells, progressive smooth muscle cell loss, and fibrosis of the media. Pathogenic mutations alter the number of cysteine residues in the extracellular domain of NOTCH3 (Notch3 ECD), leading to its abnormal accumulation in the GOM deposits. Vascular smooth muscle cell has been identified as the primary target cell in this disease. Pathophysiological processes leading from NOTCH3 mutations to smooth muscle cell loss remain poorly understood.

The investigators propose to study these mechanisms by reprogramming skin cells to become stem cells and then differentiating them to vascular smooth muscle cells.

The hypothesis of this study is that the differentiated smooth muscle cells will display the characteristic features of CADASIL, ie, Notch3 ECD accumulation and GOM deposits.


title: Etude génétique Des Arméniens

summary: This study aims at better understanding the genetic structure of the Armenians, an old population whose genetics has not been the subject of many studies. We will study 500 individuals whom grandparents originate from different regions of Armenia. Each individual will be genotyped using a large panel of genetic markers. Principal component analysis will be used to analyze the genetic structure of this population.


title: Phase II Open Label Study Using Triheptanoin in Patients With Glucose Type 1 Transporter Deficiency GLUT1-DS

acronym: GLUT-HEP

summary: The purpose of this project is to study the efficacy of triheptanoin oil in patients with GLUT1 deficiency syndrome.

ReferenceCitation: Mochel F, Hainque E, Gras D, Adanyeguh IM, Caillet S, Héron B, Roubertie A, Kaphan E, Valabregue R, Rinaldi D, Vuillaumier S, Schiffmann R, Ottolenghi C, Hogrel JY, Servais L, Roze E. Triheptanoin dramatically reduces paroxysmal motor disorder in patients with GLUT1 deficiency. J Neurol Neurosurg Psychiatry. 2016 May;87(5):550-3. doi: 10.1136/jnnp-2015-311475. Epub 2015 Nov 3.


title: Recherche et caractérisation de Nouveaux gènes impliqués Dans la déficience Intellectuelle.

acronym: GeneDefi

summary:
Intellectual disability (ID) occurs in 2 to 3 % of the general population but the cause is identified only in 30 to 60% of cases.

The purpose of this study is to indentify genes involved in ID with new genetics tools (SNP-arrays, next generation sequencing...) and establish genotype-phenotype correlations.

ReferenceCitation: Nava C, Lamari F, Héron D, Mignot C, Rastetter A, Keren B, Cohen D, Faudet A, Bouteiller D, Gilleron M, Jacquette A, Whalen S, Afenjar A, Périsse D, Laurent C, Dupuits C, Gautier C, Gérard M, Huguet G, Caillet S, Leheup B, Leboyer M, Gillberg C, Delorme R, Bourgeron T, Brice A, Depienne C. Analysis of the chromosome X exome in patients with autism spectrum disorders identified novel candidate genes, including TMLHE. Transl Psychiatry. 2012 Oct 23;2:e179. doi: 10.1038/tp.2012.102.

location_facility: CRICM - UPMC/Inserm UMR_S975/CNRS UMR7225, Groupe Hospitalier de la Pitié-Salpêtrière,


title: Study of the Influence of Sleep on Hemodynamic Parameters in Patients With Sleep Disorders

acronym: HATS

summary: Several epidemiological studies in large cohorts suggest a strong association between sleep duration, complaint of insomnia and risk of hypertension.These findings suggest an important role of sleep quality in development of hypertension. Principal limitations of these studies are the cross-sectional study design, self-report sleep duration and poor measurement of blood pressure. The investigators propose to study an insomniac population with complete evaluation of quality and quantity of sleep, associated to complete hemodynamic measurement of hypertension.

location_facility: centre du sommeil et de la vigilance, Hotel Dieu


title: Evaluation de l'efficacité thérapeutique de la Stimulation magnétique transcrânienne répétée Sur le Traitement du Craving à l'Alcool et la prévention de la Rechute Alcoolique à 6 Mois Chez Les Sujets dépendants et Des Facteurs génétiques déterminant la réponse thérapeutique

summary: Prior research in substance dependence has suggested potential anti-craving effects of repetitive transcranial magnetic stimulation (rTMS) when applied to the dorsolateral prefrontal cortex (DLPFC). The aim of the investigators study was to investigate the effect of high frequency rTMS of the left dorsolateral prefrontal cortex compared to sham stimulation on craving and alcohol consumption.


title: Identification of HCV Specific T Cells Using Tetramer Technology - TETRA Study

acronym: TETRA

summary:
Nearly 175 million people worldwide are infected by Hepatitis C Virus (HCV), close to 3% of the global population. Contrary to other chronic infections such as HIV, clearance of HCV is possible. While much is now known about the response to treatment in chronic HCV patients, the fact that acute HCV infection is typically asymptomatic (~80% of patients show no clinical signs) has made it challenging to define the mechanisms involved in spontaneous clearance.

Immune protection against HCV is thought to be largely dependent upon the CD8 T cell response. Therefore using the latest T cell detection technology the investigators will develop a panel of tetramers specific for all potential HCV epitopes. To produce the tetramers the investigators will utilize HLA ligand exchange technology which allows the production of very large collections of peptide-HLA multimers for T cell staining. The investigators have already performed a large scale identification of HCVg1 and HCVg4 CD8 T cell epitopes using published viral sequences and algorithm prediction databases. Using this information the investigators are currently in the process of developing collections of peptide-HLA multimers for T cell staining. Therefore the investigators require large lymphocyte pools from HCV+ patients to test both the sensitivity and accuracy of each tetramer on the CD3+CD8+ T cells.

The investigators wish to examine cells from patients infected with HCV g1 and HCV g4 to be able to test and compare the frequency of possible conserved epitopes present in both HCVg1 and HCVg4 infections. Once developed this technique will allow us to examine all virus-specific CD8 T cells present in patients with acute or chronic disease, and on smaller quantities of blood. The development of these technologies will also allow us to tailor such future diagnostic tests to local populations where a viral subspecies is prevalent; for example using North-African HLA alleles for HCVg4 epitopes.

The work carried out using such assays will provide important immunological correlates of viral clearance that will impact vaccine design for HCV infections. Finally, the identification of protective CD8 T cells specific for HCV may allow new diagnostic tools with predictive powers of disease progression that can be used on any flow cytometer machine.


title: Adaptation Sensorimotrice, Cervelet et Mouvements Anormaux: Projet d'étude Oculomotrice

acronym: MOUVADOC

summary:
Dystonia is a movement disorder characterized by involuntary, sustained, often repetitive muscle contractions of opposite muscles that lead to abnormal twisting movements or odd postures. Essential tremor is a slowly progressive neurologic disorder characterized by the appearance of a tremor during the voluntary movement. The pathophysiology of dystonia or essential tremor is not fully elucidated. Dystonia and essential tremor are associated with dysfunction of the sensorimotor basal ganglia-cortical network and involvement of the cerebellum and cerebellar pathways has also been recently suggested.

The investigators propose to study 30 patients having a primary dystonia (15 DYT11 genetically documented), 15 patients having an essential tremor without deep brain stimulation and 15 patients having an essential tremor with deep brain stimulation.A group of 30 healthy volunteers will be recruited and tested according to the same modalities. They will be paired in sex and age. 30 patients having a Parkinson disease will be also tested.

Eye position will be sampled with a video-based monocular eye tracker (SMI, Germany) before and immediately after an adaptation task. Saccade adaptation is evaluated as the percentage change in the mean saccade amplitude between pre-test and post-test.

Expected results:

no or fewer alteration of the performance to the adaptation task in the Parkinson group than in the Essential Tremor group/ dystonia group.
abnormal reactive saccade backward adaptation in the Dystonia group and Essential Tremor group, providing further neurophysiological evidence of cerebellar dysfunction.

location_facility: : Fédération des Maladies du Système Nerveux


title: Dopaminergic Reactivity In Idiopathic Generalized Epilepsy: A "Proof Of Concept" Clinical, Pharmacological And Neurophysiological Study

acronym: BYE BYE DOPA

summary:
The objective of the present study is to assess dopaminergic reactivity with behavioural markers (i.e. yawning and blinking) in patients with idiopathic generalized epilepsy compared to matched healthy controls, after injection of either low dose of apomorphine or placebo.

Other parameters will be recorded: biochemical (prolactin, GH) and neurophysiological (Spike-Waves Discharge: SWD rating). Safety parameters will be recorded to assess tolerance.

ReferenceCitation: Ahmad S, Fowler LJ, Whitton PS. Effect of acute and chronic lamotrigine on basal and stimulated extracellular 5-hydroxytryptamine and dopamine in the hippocampus of the freely moving rat. Br J Pharmacol. 2004 May;142(1):136-42. Epub 2004 Mar 22.

ReferenceCitation: Ahmad S, Fowler LJ, Whitton PS. Lamotrigine, carbamazepine and phenytoin differentially alter extracellular levels of 5-hydroxytryptamine, dopamine and amino acids. Epilepsy Res. 2005 Feb;63(2-3):141-9.

ReferenceCitation: Aymard G, Berlin I, de Brettes B, Diquet B. Pharmacokinetic-pharmacodynamic study of apomorphine's effect on growth hormone secretion in healthy subjects. Fundam Clin Pharmacol. 2003 Aug;17(4):473-81.

ReferenceCitation: Biraben A, Semah F, Ribeiro MJ, Douaud G, Remy P, Depaulis A. PET evidence for a role of the basal ganglia in patients with ring chromosome 20 epilepsy. Neurology. 2004 Jul 13;63(1):73-7.

ReferenceCitation: Blin O, Masson G, Azulay JP, Fondarai J, Serratrice G. Apomorphine-induced blinking and yawning in healthy volunteers. Br J Clin Pharmacol. 1990 Nov;30(5):769-73.

location_facility: CIC Department - University Hospital of Grenoble


title: A Phase II Study With Tumor Molecular Pharmacodynamic (MPD) Evaluation of Oral mTOR-inhibitor Everolimus (RAD001) 10 mg Daily in Patients Suffering From Classic or Endemic Kaposi's Sarcoma

summary: Classic Kaposi's sarcoma (CKS) is an angioproliferation associated with human herpes virus 8 (HHV8), which sometimes requires systemic treatment. Rapamycin and everolimus are mTOR inhibitors. The PI3K-AKT-mTOR pathway is activated in CKS.The aim of this study is to evaluate the rate of clinical response and tolerance to everolimus 10mg/d in CKS. Patients suffering from CKS will be enrolled in a multicenter two-stage phase II trial. At inclusion, all patients will have at least 10 lesions or more than one limb or 3% of body surface affected, in the absence of symptomatic visceral CKS. The primary endpoint is objective response to everolimus after 6 months therapy (complete or partial response per ACTG criteria). The trial is planned using Simon's minimax two-stage design to demonstrate a response rate of 50% as compared to 20% with type I error rate 2.5% and power of 90%. Accordingly, 11 patients will to be enrolled in the first stage and provided at least 3 patients responded, 15 patients will be accrued in a second stage.


title: Neuropsychological and Anatomical Study of Concept Formation in Frontal Patients

summary:
The capacity of concept formation is not well understood, even if a link is supposed with the functioning of the frontal lobes.

Our aim is to better understand the cognitive mechanisms underlying this function and to try to correlate the performance with atrophy of the frontal lobe in neurodegenerative diseases involving this region (frontotemporal lobar degeneration and progressive supranuclear palsy).


title: Study of Abnormal Structure and Bone Density at the Feet of Diabetic Patients

summary:
Assumptions and Objectives: The working hypotheses are: 1 - subjects with type 1 diabetes and / or type 2, compared to subjects without diabetes are at risk for osteopenia and / or abnormal bone structure the foot (calcaneus and ankle) can lead to bone deformities, fractures and final stage of Charcot foot. These anomalies are favored by the presence of peripheral neuropathy and plasma levels of advanced glycation end products higher than in diabetic subjects without bone abnormalities.

The objectives of this research are to evaluate these anomalies quantitative and qualitative bone in the foot (calcaneus and ankle) through the use of MicroScanner. In parallel a whole body bone mineral density (BMD) and calcaneal ultrasound will be performed to measure bone mineral density as realized in clinical practice in a defined population of patients with type 1 or type 2. These bone abnormalities will be correlated with the presence of peripheral neuropathy and the rate of advanced glycation end products of proteins and reference to parameters of chronic inflammation and oxidative stress to better understand the pathophysiology and target a population at risk.

The importance of this study is paramount in the management of diabetic foot. Indeed for the moment we are dealing primarily the consequences of diabetes impact bone when bone deformities have appeared with their attendant disability and the risk of recurrent infections in areas of friction in this fragile environment. The ultimate goal is to target people with diabetes have abnormal bone subclinical and take care to avoid changes to bone deformities and find ways to treat them.


title: Study of a Large Family With Congenital Mirror Movements : From Underlying Pathophysiology to Culprit Gene Identification : MOMIC

acronym: MOMIC

summary: Mirror movements are involuntary, symmetrical and simultaneous movements occurring on one side of the body that accompany controlateral voluntary movements. Congenital mirror movements (CMM) are characterized by childhood onset and the absence of additional manifestations. The aim of this study is to unravel the pathophysiology of the CMM that remains poorly elucidated. The combination of imaging studies and neurophysiological studies using transcranial magnetic stimulation in a homogeneous and relatively large group of patient is likely to allow us to better understand the underlying pathophysiology of the disorder. Using a linkage analysis approach we will try to identify a locus associated with CMM and related candidate genes.

location_facility: Fédération des Maladies du Système Nerveux, Hôpital Pitié Salpétrière


title: Repetitive Transcranial Magnetic Stimulation of the Posterior Parietal Cortex in Patients Suffering From Gilles de la Tourette Syndrome

acronym: rTMSPPCGT

summary: Repetitive transcranial stimulation (rTMS) of the posterior parietal cortex will be applied daily over five days in adult Gilles de la Tourette patients. This approach aims at reducing premonitory sensations believed to induce tics. Patients will be randomized to an active or placebo (sham) group in a crossover design.


title: Etude Multicentrique en Population de la susceptibilité génétique à Faire Une Mort Subite

acronym: CARTAGENE

summary: Sudden death is a major problem in industrially developed countries. Despite a decline in ischemic heart disease mortality and the progress has been made in resuscitation, treatment of sudden death victims is frequently unsuccessful. the ideal solution would be to prevent the disease process that causes the initial episode of cardiac arrest. Parental sudden death is an independent risk factor for sudden death. So, detect a gene predisposing to sudden death may help provide better identification of subjects at high risk of cardiac arrest. This research is a genetic study of sudden cardiac death, recruited 2000 subjects in out-of-hospital cardiac arrest.