title: Retrospective and Prospective, Multicenter Study on T.E.S.S.® V3 (Implants and Instrumentation)

summary: This is a multicenter, retrospective and prospective, non-controlled post market surveillance study. The objectives of this study are to confirm safety, performance and clinical benefits of the T.E.S.S.® Version 3 Anatomic and Reverse Modular Total shoulder prosthesis and its instrumentation.

time_perspective: Other

lead_sponsor: Zimmer Biomet


title: Randomized Controlled Study Evaluating The Contribution of a Hypnosis Intervention During a Lumbar Puncture in the Neurology Department.

acronym: HYPNOPLUS

summary: The purpose of this study is to assess the effect of hypnosis, as add on therapy, on patients requiring a lumbar puncture (LP) as part of their medical management.

study_start_date_type: Actual

status: Recruiting

study_completion_date_type: Anticipated

study_type: Interventional

design_allocation: Randomized

primary_purpose: Supportive Care

enrollment_type: Anticipated

lead_sponsor: University Hospital, Grenoble

location_facility: Neurology department of Grenoble University Hospital

intervention_type: Other

lead_sponsor_type: academique

status_simplified: Ongoing


type: Other Identifier

title: Post-surgical Patient Experience: Definition of New Indicators

acronym: CALEX

summary: The success of a surgical intervention is evaluated by different indicators: survival, functional after-effects, regression of the clinical signs that led to the intervention, rate of re-operation or re-hospitalization, etc. However, the success of an intervention and, more generally, the quality of care are complex notions that include several aspects: technical, human, narrative, relational, ethical and systemic aspects. Thus, quantitative criteria are very useful and reliable indicators, but they must be integrated into a more global vision. In particular, quality of care is not perceived in the same way by caregivers, patients and their families. The integration of the patient experience in the design and implementation of quality indicators opens new perspectives for reflection and action. For example, patient-tracer questionnaires, which make it possible to evaluate the patient's experience after the fact, have been developed by the High Authority for Health (HAS) and are now part of the quality indicators in hospitals. Some studies have adopted a qualitative approach to collect the patient's experience after surgery. However, there is currently no questionnaire based on the patient's experience evaluating the success of a surgical procedure. The objective of this work will be to report meta-narratives based on patients' experiences and in a second step to build a quality questionnaire of the surgical pathway focused on patients' needs.

study_start_date_type: Anticipated

status: Not yet recruiting

primary_purpose: Other

ipd_sharing: No

lead_sponsor: Centre Hospitalier Intercommunal Creteil

location_facility: Centre Hospitalier Intercommunal Créteil

intervention_type: Behavioral


title: Impact of Listening to Music on Anxiety Postoperative in a Postanesthesic Care Unit (PACU) After Spinal Anesthesia

acronym: MusicAnx-SSPI

summary: Our hypothesis is that listening to music has a beneficial effect on the French population receiving spinal anesthesia for a scheduled procedure. We think we can reduce anxiety when switching to SSPI, using creative music therapy software (Music Care) French validated by clinical research.

lead_sponsor: CHU de Reims


title: Prevalence and Risk Factors of Dermatoporosis in Patients Over 75 Years of Age Hospitalized in Reeducation

acronym: Dermatoporose

summary:
The term dermatoporosis, by analogy to osteoporosis, was proposed by Professor Saurat to define all the manifestations linked to skin aging leading to fragility and skin failure. With age, the gradual disappearance of hyaluronic acid and its CD44 cell receptor leads to the degeneration of the extracellular matrix and then to the loss of the protective mechanical functions of the skin. It thus appears an alteration of the viscoelasticity of the skin. The most common skin manifestations of dermatoporosis are mainly located on the upper limbs. Several clinical manifestations characterize dermatoporosis: skin atrophy, senile purpura, stellate pseudo-scars, delayed healing and finally dissecting skin hematoma. There are 4 evolutionary stages of dermatoporosis described by Professor Saurat and by Doctor Kaya, in 2007: Stage 1: strong thinning of the skin with senile purpura and stellate pseudo-scars. Stage 2: manifestations of the previous stage and small, localized skin lacerations resulting from a cleavage between the dermis and the epidermis. Stage 3: more and larger skin lacerations with a noticeable delay in healing Stage 4: the progression of the lesions described above leads to the formation of dissecting skin hematomas which may progress to skin necrosis. (Saurat JH Dermatoporosis - the functional side of skin aging. Dermatology 2007 and Kaya G, dermatoporosis: A chronic cutaneous insufficiency / fragility syndrome. Clinicopathological features, mechanisms, prevention and potential treatments. Dermatology 2007).

A study by Mengeaud et al found a significant association between severe renal failure and dermatoporosis. Two studies, one in Toulouse and the other in Finland, looked at the prevalence and risk factors of dermatoporosis in patients over 60 years of age. The observational study on 202 patients over 60 years old in Toulouse shows a prevalence of 32%, with preferentially localization on the upper limbs. Stage 1 is the most common. Multivariate statistical analyzes show that dermatoporosis is significantly associated with the use of local and oral corticosteroids, anticoagulants, and chronic renal failure. On the other hand, it has not been shown to be associated with diabetes and the patient's sun exposure.Another study, dating from 2018 also found that kidney failure, taking antiaggregants and anticoagulants, corticosteroid therapy (local or systemic) are risk factors for dermatoporosis. However, no study has been carried out on a geriatric population, and the association between phototype, sun exposure and dermatoporosis has to our knowledge never been systematically investigated in the few studies conducted.

status: Completed

study_completion_date_type: Actual

study_type: Observational

time_perspective: Prospective

enrollment_type: Actual

ipd_sharing: Undecided

lead_sponsor: Assistance Publique - Hôpitaux de Paris

status_simplified: Completed


title: Etude Pilote d'évaluation de l'efficacité de l'ETP Sur l'Insomnie Chronique

acronym: ETP-INSOMNIE

summary:
20 to 30% of the general population suffers from chronic insomnia. Cognitive behavioral therapy (CBT) is the first-line treatment, but unfortunately its implementation is complex. Long waiting times for a consultation / exploration, too short a consultation period, non-reimbursement of specialists and a lack of trained staff make the current care of insomniac patients difficult. Patients are thus treated late, often with heavy drug treatment, dependence on sleeping pills, difficult withdrawal and / or reactive mood disorders. The treatment is therefore limited to advice on sleep hygiene and a restriction of time spent in bed without ultimately intervening in the cognitive domain. Therapeutic education consists of empowering the patient in the management of chronic insomnia through group education workshops. The patient learns the principles of normal sleep, the way in which sleep evolves with aging, the dangers of treatments as well as the rules of sleep hygiene and the behaviors to modify to sleep well. In addition to benefiting from sharing of experience with other patients, therapeutic education makes the care pathway smoother and considerably reduces the long waiting times of the traditional care pathway in consultation.

The study investigators hypothesize that therapeutic education is more effective as a treatment for chronic insomnia than traditional management in individualized consultation (IC). Thus, therapeutic education could constitute an effective alternative to CBT.

primary_purpose: Treatment

lead_sponsor: Centre Hospitalier Universitaire de Nīmes


title: Detection of Significant Coronary Artery Disease by Promising Biomarker: A2A Adenosine Receptor (A2AR) Assays

acronym: ADOCAD

summary:
Transversal, national, multi-center study with progressive recruitment designed to assess the diagnostic accuracy of A2AR expression for the identification of significant obstructive CAD (FFR<0.8) of patients suspected of CCS compared to the gold standard.

To assess the diagnostic accuracy of the A2AR profile (i.e. KD/EC50) for identifying myocardial ischemia in patients with suspected CCS compared to the gold standard inducible myocardial ischemia.
To determine the best threshold value for A2AR expression for identifying significant obstructive CAD (FFR<0,8) in patients with CCS, and to estimate the diagnostic performances associated with the identified threshold
To determine the best threshold value for A2AR profile (i.e. KD/EC50) for identifying myocardial ischemia (See annex 2) in patients with CCS and to estimate the diagnostic performances associated with the identified threshold.

primary_purpose: Diagnostic

lead_sponsor: Assistance Publique Hopitaux De Marseille

location_facility: Assistance Publique Hopitaux de Marseille

intervention_type: Biological


type: EudraCT Number

title: Administration of Fibrinogen Concentrate for Refractory Bleeding in Hematological Patients With Intensive Chemotherapy-induced Thrombocytopenia - Analysis Using Viscoelastic Haemostatic Assay (FORMAT)

acronym: FORMAT

summary: Platelet transfusions are widely employed to prevent or treat bleeding episodes in patients with thrombocytopenia. Patients with bone marrow failure secondary to haematological malignancy and chemotherapy frequently receive prophylactic platelet transfusion when platelet level reaches 10x109.L-1, to avoid spontaneous major bleeding. Due to immune or nonimmune factors, platelet refractoriness may be observed and is defined as a repeated suboptimal response to platelet transfusions with lower-than-expected post-transfusion count increments. The management of patients with alloimmunization is complex and prophylactic platelet support is no longer indicated. Therefore, platelet refractoriness remains a clinically challenging complication.

lead_sponsor: Centre Hospitalier Universitaire de Saint Etienne

intervention_type: Drug


title: A Phase 1, Double-blind, Randomized, Placebo-controlled, First-in-human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Oral Doses of ALG-055009 in Healthy Volunteers and Subjects With Hyperlipidemia, and an Open-Label Assessment of Bioavailability and Food-effect in Healthy Volunteers

summary: A Randomized Study of ALG-055009 Drug to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses in Healthy Volunteers and Subjects with Hyperlipidemia

status: Active, not recruiting

lead_sponsor: Aligos Therapeutics

lead_sponsor_type: industriel


title: Ventilator-associated Pneumonia Ecology Comparison in a French ICU Center NIMES Between First and Second Wave of COVID-19 : a Retrospective Monocentric Descriptive Study

acronym: ECOLCOVID

summary: In December 2019, a new pandemic emerged, the COVID-19 disease caused by a SARS-Cov-2 virus. One of the most common symptoms of COVID-19 is mainly respiratory failure and patients requires assistance by mechanical ventilation. Ventilator-associated pneumonia (VAP) is a risk of this assistance. Since the beginning of the pandemic, Standard of care have evolved with new data. The prevalence of these VAPs seems significantly higher in the population of patients with ARDS COVID-19 (40-50%) and their ecology seems to have evolved over time, particularly in terms of bacterial resistance. Investigators want to describe and compare this evolution of bacterial and fungal ecology as well as identify potential risk factors that may be associated with these changes in ecology during different waves.

time_perspective: Retrospective

location_facility: CHU de Nîmes - Hôpital Universitaire Carémeau


title: MAster Protocol Studying the Impact of Blood Biopsy on Screening, Diagnosis, Diagnostic and Follow-up of Solid Cancer in Adult

acronym: CIRCAN MAP

summary: This exploratory study will focus on the development of the analyses of blood biomarkers to better understand the circulating biomarkers associated with cancer diagnosis, treatment efficacy and progressive disease

lead_sponsor: Hospices Civils de Lyon


title: Efficacy of Prolonged Anticoagulation for Primary Prevention of Venous Thromboembolic Disease in Autoimmune Hemolytic Anemia: a Prospective, Phase II, Randomized, Multicenter Study

acronym: API-AHAI

summary:
Autoimmune hemolytic anemia (AIHA) is a rare autoimmune disease (incidence <1/100,000 population) responsible for the destruction of red blood cells by the host immune system, notably through the action of autoantibodies.

Apart from complications related to anemia, the occurrence of venous thromboembolism (VTE) in this population is frequent, estimated at 20-27%. The risk of VTE is highest during the period of hemolysis, especially during the first 3 months after the diagnosis of AIHA. This risk is 7.5 [4.7; 12.0] times greater than in the general population. No clinical predictive factor for VTE was identified and the usual factors (cancer, previous VTE, bed rest >3 days, surgery, age >70 years, heart or respiratory failure, myocardial infarction, stroke, obesity, hormone replacement therapy) were not considered. Several biological risk factors have been suggested (depth of anemia, bilirubin level, leukocyte count, antiphospholipid antibodies) but have not been confirmed in other studies.

AIHA is therefore a risk factor for VTE in its own right, and the National Diagnostic and Care Protocol (NDCP) recommends the implementation of VTE prevention during acute hemolysis (Grade C). However, the value of this prophylaxis has never been prospectively evaluated and its duration is empirical. In practice, low-molecular-weight heparin (LMWH) is generally used during "flare-ups" of AIHA (diagnosis and relapse) in hospitalized patients, but is rarely continued beyond the hospital phase when VTE also occurs in ambulatory patients.

Thus, we hypothesize that prolonged preventive anticoagulation during the 12-week risk period following diagnosis or relapse of AIHA could decrease the incidence of VTE.

In orthopedic surgery, this strategy has been proven to decrease VTE from 50% to 10-15%. In certain high-risk medical situations, prolonged prophylaxis with apixaban has been shown to decrease the occurrence of VTE from 10.2% to 4.2% in solid cancers4 and from 4-11% to 2% in myeloma.

primary_purpose: Prevention

lead_sponsor: Centre Hospitalier Universitaire Dijon


title: Osteopathic Consultation in the Emergency Department for Fresh Lateral Ligament Sprain : a Randomized Controlled Trial

acronym: OASED

summary:
The study consists in recruiting patients with ankle sprains who visit the emergency department (ED).

Each patient will be tested by an osteopath who we will measure pain, swelling and/or edema, and mobility of the ankle. Patients will be asked to reproduce exercises such as to hold on one foot, to stand on tiptoes...

Then, patients will be divided into two groups. The first group will undergo medical treatment during the ED visit, while the second group will undergo osteopathic treatment.

Three time points will be planned. The first one will be the patient's consultation in the ED where treatment will be carried out according to its assignment, as well as the clinical measures previously described. The second time point will be seven days later (plus or minus three days), where only clinical measurements will be performed. The third time point will be three weeks later (plus or minus three days), when the ankle sprain has consolidated, in order to carry out the clinical measurements again.

These clinical measurements will allow to evaluate the effectiveness of a single osteopathic consultation in the ED. The investigators expect a reduction in immediate pain, and thereafter, a reduction in swelling, and an improved mobility and stability of the ankle.


title: Impact of Obesity, Chronic Kidney Disease and Type 2 Diabetes on Human Urinary Stem Cells

acronym: URISTEM

summary:
Obesity is at risk for the development of chronic kidney disease but the involved mechanisms are not known (Navarro et al. 2015). Establishing the link between obesity and kidney damage is difficult. Indeed, kidney function measurement lacks precision in obese people (Lemoine et al. 2014) and requires expensive methods such as measurement of 99mTc-DTPA clearance. Biopsies are too invasive for the detection of emerging kidney damage or for the following of the kidney function. Therefore new tools are required for the early identification of at risk individuals for the kidney damage complication.

Mesenchymal stem cells may represent such a relevant tool. These cells are present in a large number of organs, including kidney (Costa et al. 2020).

In addition to be differentiated cells progenitors (Dominici et al. 2006), they also support immunosuppressive, anti-fibrotic and pro-angiogenic functions that have been used for the treatment of kidney fibrosis (Usunier et al. 2014). Therefore, mesenchymal stem cells contribute to tissue homeostasis and their alterations may reflect organ dysfunctions. Indeed, mesenchymal stem cells from obese adipose tissue lose their immunosuppressive (Serena et al. 2016) and differentiation (Gustafson et al. 2009) functions and contribute to fibrosis (Keophiphath et al. 2009) and inflammation (Lee et al. 2010; Gustafson, Nerstedt, et Smith 2019). It is thus probable that kidney dysfunctions are associated with functional alterations of kidney mesenchymal stem cells.

The collection of mesenchymal stem cells from kidney can easily be performed from urine and next cultivated for amplification. They are called urine stem cells (USC).

From our experience with obese mouse adipose stem cells, we observed that functional changes of stem cells preceded adipose tissue dysfunctions. Functional signatures of mesenchymal stem cells are thus representative of changes occuring in the function of the tissue notably in answer to obesity. These features could be used to identify obese people presenting ongoing alterations of kidney function, before clinical manifestations of kidney dysfunction. Because kidney mesenchymal stem cells are easy to isolate from urine, their collection is compatible with the follow up of patients and can be applied to a large number of individuals, including the younger. USC could represent a valuable tool to detect progression towards kidney damage.

In this project we plan to analyse USC alterations induced by obesity and to identify signatures associated with the progression towards kidney damage and type 2 diabetes. The goal is to evaluate USC as potential marker for the non invasive monitoring of patients in answer to a need that is not achieved by the present available approaches.


title: Cardio-visual Stimulation in Augmented Reality for Pain Reduction

acronym: HEART

summary: The objective of this study is to evaluate the feasibility and efficacy of an Augmented Reality (AR) biofeedback intervention to alleviate pain symptoms in individuals suffering from chronic pain of the hand and/or the forearm.

lead_sponsor: Union de Gestion des Etablissements des Caisses d'Assurance Maladie - Nord Est

location_facility: Institut Régional de Médecine Physique et de Réadaptation

intervention_type: Device


title: Evaluation of Physical Capacities Within the Company and Effect of a Personalized Versus Traditional Training Program on the Quality of Life of Sedentary Employees: Randomized Controlled Trial

summary:
The practice of a physical activity, even moderate, plays an important role in the prevention and the management of the main chronic non-communicable diseases (cardiovascular diseases, certain cancers, diabetes, obesity, osteoporosis ...) as well as by improving psychological health. Several studies have shown that physical activity has a positive impact on the economy of companies via the reduction of absenteeism and the improvement of productivity. However, it seems important to individualize these recommendations in order to prescribe the best possible dose of physical activity for each individual. In this project, the investigators want to test the physical qualities of employees in order to prescribe the best possible dose of physical activity with the ultimate goal of improving quality of life.

The originality of this project is to evaluate physical capacities directly within the company of the participants instead of hospital unit.


title: Intestinal Permeability in Obesity of Intercellular Tight Junctions to Metabolic Complications

acronym: LEAKY GUT

summary: In rodents, obesity is associated with changes in tight junctions' structure in small intestine, which impacts intestinal permeability and results in metabolic complications. Few data exist in human. We hypothesized that intestinal permeability is altered in obese subjects in comparison to lean subjects, linked to metabolic and inflammatory status and that these alterations are modified after gastric bypass.

status: Terminated

design_allocation: Non-Randomized

status_simplified: Unknown


title: Effect of the Alpha-galacto-oligasaccharides on Weight Loss in Overweight or Moderately Obeses Adults : A Randomized Controlled Double Blinded Trial Versus Placebo

summary: Clinical intervention on overweight or moderately obeses adults. The objective of this trial is to demonstrate the superior eficacy of Alphagos to placebo on weight loss during a low-calorie diet of 12 weeks. The superiority is judged on body weight. Change in cardiometabolic risk factors through the intervention have been evaluated as secondary endpoints

lead_sponsor: Olygose

location_facility: Centre d'Investigation Clinique Paris-Est/ Bâtiment Antonin Gosset Hôpital de la Pitié Salpêtrière- 56 Boulevard Vincent Auriol

intervention_type: Dietary Supplement


title: Modulating Speech Perception With Current Stimulation (SPEECHSTIM)

acronym: SPEECHSTIM

summary: This study aims to further develop tACS as a tool to improve speech perception, by manipulation of brain-speech synchronisation ("entrainment"), thereby transforming a promising approach into a technique that can benefit to society on a large scale.

primary_purpose: Basic Science

ReferenceType: background

ReferenceCitation: van Bree S, Sohoglu E, Davis MH, Zoefel B. Sustained neural rhythms reveal endogenous oscillations supporting speech perception. PLoS Biol. 2021 Feb 26;19(2):e3001142. doi: 10.1371/journal.pbio.3001142. eCollection 2021 Feb.

ReferenceCitation: Zoefel B, Davis MH, Valente G, Riecke L. How to test for phasic modulation of neural and behavioural responses. Neuroimage. 2019 Nov 15;202:116175. doi: 10.1016/j.neuroimage.2019.116175. Epub 2019 Sep 6.

ReferenceCitation: Zoefel B, Allard I, Anil M, Davis MH. Perception of Rhythmic Speech Is Modulated by Focal Bilateral Transcranial Alternating Current Stimulation. J Cogn Neurosci. 2020 Feb;32(2):226-240. doi: 10.1162/jocn_a_01490. Epub 2019 Oct 29.

lead_sponsor: University Hospital, Toulouse

intervention_type: Procedure


title: Assessment of the Acceptability of a Humanoid Robot at Home for Children With Cochlear Implants - H2R2

summary: The quality of the rehabilitation of deafness in children with cochlear implantation is a major prognostic factor for the outcome on speech comprehension and oral expression. This rehabilitation is carried out cooperatively by the hospital cochlear implantation team, and by a speech therapist located near the child's home. The multi-weekly sessions represent a constraint for the child and his parents. Complementary training work at home would make it possible to balance the equity in the distribution of care in the territory, and should promote the progress of the child, who is more inclined to use a tool available at home.

ReferenceCitation: Diehl JJ, Schmitt LM, Villano M, Crowell CR. The Clinical Use of Robots for Individuals with Autism Spectrum Disorders: A Critical Review. Res Autism Spectr Disord. 2012 Jan;6(1):249-262.

location_facility: University Hospital Toulouse - Service d'ORL, ORL pédiatrique et Otoneurologie


title: Assessment of Brain Activity Associated With Inhibition of Action in Attention-deficit Hyperactivity Disorder

acronym: INHIB'MOV

summary: Inhibitory control allows individuals to suppress unwanted actions and to resist irrelevant stimuli. It is thought to be a core deficit in Attention-deficit/hyperactivity disorder (ADHD). The present study aims at evaluating this deficit in adults with ADHD. Executive and inhibitory capacities, as well as the neural mechanisms underlying inhibitory control, will be assessed in adults with ADHD and two control groups of participants.


title: Defining the Role of the Skin Microbiome in Vitiligo and Immune-related Adverse Events in Advanced Melanoma Patients Treated With Anti-PD1

acronym: SKINBIOTA

summary: The skin microbiome has been implicated in several cutaneous autoimmune pathologies such as psoriasis and atopic dermatitis. However, its role in vitiligo and vitiligo lesions occuring in patients receiving anti-PD-1 for metastatic melanoma

lead_sponsor: University Hospital, Bordeaux

location_facility: Service de Dermatologie - Hôpital Saint-André


title: 3D Modelling and Morphometric Characterisation of the Skull Deformations in Congenital Muscular Torticollis : Development of Physiopathological Sequences

summary: The congenital muscular torticollis (CMT) is defined by an abnormal posture of the head and the neck compared to shoulders' level of the newborn. The mainly affected muscle is the sternocleidomastoid muscle (SCM) causing a lateral inclination of the head on the side affected by the CMT and a rotation on the opposite side. CMT comes with asymmetricalndeformation of the skull or plagiocephaly, facial asymmetry, skull and cranio-vertebral deformatioes in CMT are the results of a complex mechanism of biomechanical stresses upon a developing skull. The hypothesis of a traction force on the base of the skull from the SCM could explain most of all the asymmetrical deformatios encountered in CMT. It would be associated to a compression force at the occipital level

ipd_sharing_description: NC

lead_sponsor: University Hospital, Montpellier


title: Functional Near Infra-Red Spectroscopic Study of Central Auditory System Cortical Functional Reorganization in Unilateral Deaf Children

acronym: SUN

summary: This study aims to compare the auditory cortical activity in response to monaural and binaural stimuli, measured by functional Near-Infrared Spectroscopy (fNIRS) between Single-sided Deaf (SSD) Children, and Normal-Hearing (NH) children from 5 to 16 years. Binaural audiological performance, speech skills and quality of life (QoL) will be compared between the 2 groups and links to with the cortical activity will be assessed.

status: Unknown status


title: Investigation of Urinary Biomarkers for the Diagnosis of Insulin Resistance

acronym: BIOMUIR

summary:
The study aims at the identification and the quantification of urinary branched-chain amino acids (BCAAs) by mass spectometry in healthy subjects and patients with insulin resistance and correlating urinary BCAAs with HOMA index.

Blood and urine levels of BCAAs will be correlated with HOMA index to assess and quantify insulin resistance.

Identification and quantification of urine BCAAs by an innovative method based on synthetic biology will also be performed.

Correlations between mass spectometry and the innovative detection method of BCAAs will be searched.

intervention_type: Diagnostic Test


title: Amyloidosis Typing Using Mass Spectrometry-based Proteomics: a New Accurate Tool for Difficult Typing

acronym: TYPAMYL

summary: The main objective is to establish that a new technique of amyloidosis typing by Proteomics (based on nanoLC-MS/MS mass spectrometry) allows typing in > 90% of observations in patients whose Amyloidosis is reported to have failed typing (impossible typing, uncertain or inconsistent) with the traditional anatomopathological approach, and this in a cohort of 40 patients identified consecutively in the Department of pathological anatomy and cytology of the University Hospital of Toulouse and included prospectively.

ReferenceCitation: Vrana JA, Gamez JD, Madden BJ, Theis JD, Bergen HR 3rd, Dogan A. Classification of amyloidosis by laser microdissection and mass spectrometry-based proteomic analysis in clinical biopsy specimens. Blood. 2009 Dec 3;114(24):4957-9. doi: 10.1182/blood-2009-07-230722. Epub 2009 Oct 1.

ReferenceCitation: Theis JD, Dasari S, Vrana JA, Kurtin PJ, Dogan A. Shotgun-proteomics-based clinical testing for diagnosis and classification of amyloidosis. J Mass Spectrom. 2013 Oct;48(10):1067-77. doi: 10.1002/jms.3264.


type: Registry Identifier

title: Identification of Acoustic and Perceptual Markers of Lower and Upper Motor Neuron Signs in Dysarthria of Patients With Amyotrophic Lateral Sclerosis : a Comparison With Primitive Lateral Sclerosis, Kennedy's Disease and Controls

acronym: SPEECH-ALS

summary: This study proposes to identify acoustic and perceptual markers related to upper motor neuron (UMN) degeneration and lower motor neuron (LMN) degeneration in the dysarthria of patients with amyotrophic lateral sclerosis (ALS) which involves the degeneration of both systems. ALS patients will be gathered in clinical groups according to electromyogram (EMG) and clinical signs observed in the bulbar site. UMN signs are defined as jaw clonus, gag reflex and pseudobulbar features (lability). LMN signs are defined as lingual atrophy and fasciculations. The dysarthria will be compared to dysarthria of patients involving an exclusive UMN system degeneration (in primitive lateral sclerosis) and an exclusive LMN system degeneration (Kennedy's disease). Patients will be compared to the controls who permitted to establish the standards of the "MonPaGe" tool. MonPaGe is a computerized tool based on a multidimensional and quantified assessment of voice and speech, by a set of targeted acoustic and perceptual criteria.

ReferenceType: derived

ReferenceCitation: Slis A, Lévêque N, Fougeron C, Pernon M, Assal F, Lancia L. Analysing spectral changes over time to identify articulatory impairments in dysarthria. J Acoust Soc Am. 2021 Feb;149(2):758. doi: 10.1121/10.0003332.


title: Can the Peritoneal Cavity be a Source of Regulatory B Cells to Treat Auto-immune Disease?

summary: Some subsets of lymphocytes are able to inhibit immune response and thus, could be used to control auto-immune diseases and transplant reject. In mice, the main source of those anti-inflammatory lymphocytes is the peritoneal cavity. No data are available in human. This study aims at exploring the presence of those anti-inflammatory lymphocytes in human peritoneal cavity and at determine how to expand those cells.

location_facility: CHU montpellier - department of rheumatology


title: Endometrial Cancer and Fractalkine-receptor Axis of Fractalkine

summary:
The endometrial cancers are among the most common malignancies in postmenopausal women with an incidence on the rise. It is most often a endometrioid adenocarcinoma (grade I, II, III). Other histological types are represented mainly by the clear cell carcinoma, papillary serous carcinoma, the carcinosarcoma. The main risk factors for endometrial cancer are age, obesity, diabetes, hypertension, hormone replacement therapy with estrogen and tamoxifen.

Endometrial hyperplasia usually precedes endometrial cancer is classified by degree of cytologic atypia. Tumor grade quantifies the degree of differentiation and significantly influences the prognosis. Most research has been applied to define the role of estrogen in these cancers, however an accumulation of data indicate that the general process of tumorigenesis is closely related to immune and inflammatory microenvironment of the tumor. In fact, the microenvironment may be seen as a prognostic parameter of tumors or even predictive of therapeutic response.

Recognized as the key molecules responsible for leukocyte recruitment into the tissues, the chemokine-receptor pairs are key players in the immune response, including the anti-tumor immune response but also the inflammatory response. The chemokine-receptor pairs are also involved in many other basic processes such as proliferation, survival or cell death.

The objective of this study was to evaluate the prognostic value of the expression of the chemokine fractalkine (FKN) and its receptor CX3CR1 for the development of endometrioid adenocarcinomas.

Chemokine FKN has the particularity to exist in two forms, a soluble (FKNs), like all chemokines and membrane form (FKNm). The FKNs, resulting from proteolytic cleavage of the FKNm, is provided with chémoattractantes properties. FKNm the present adhesion molecule properties.

The role of FKN in cancer biology is complex.

To date, the role of FKN in endometrial cancer has not been reported. Similarly, the precise role of FKN in the physiology of the endometrium is unknown.

Nevertheless, fractalkine is one of the most expressed in endometrial chemokines. The expression of FKN and its CX3CR1 receptor is detected in the endometrium at all stages of the menstrual cycle. The respective levels of expression of each are fluctuating and largely dependent on the cycle of stage suggesting a possible control by estrogen and progesterone control described elsewhere ovarian level and endothelial. The cells of the endometrial glandular epithelium, macrophages, neutrophils and NK cells infiltrated in this tissue as well as the endothelial cells of blood vessels express FKN. Interestingly, all the cells mentioned above express CX3CR1, except for NK cells and unlike most tissues, the CD8 cells, present in the endometrium, do not express CX3CR1.

In addition, the strongest expression of FKN and CX3CR1 cells by endometrial epithelial coincides with the maximum activity of the glandular epithelium suggesting a possible autocrine loop promoting cell proliferation of the endometrium. Concurrently with the peak of fractalkine, an accumulation of monocytes / macrophages and neutrophils is observed in the endometrium. It appears, moreover, that the balance between the soluble and membrane forms of FKN is important for positioning, infiltration and activity of immune cells within the endometrium.

Current knowledge on the involvement of FKN / CX3CR1 axis in the physiology of the endometrium, although incomplete, point unequivocally the potential role of this ligand pair / receptor in the physiology of the tissue and also suggest that a malfunction of this axis could easily cause various diseases.

Chronic inflammation of a tissue, largely dependent on macrophage infiltration rate, generally represents the tumor development. The endometrium is subjected to physiologically cyclic and regular inflammatory episodes, mirrors for the expression of chemokines and leukocyte infiltration. However, prolonged leukocyte infiltration establishing chronic or prolonged inflammation of the endometrium could help shape a favorable microenvironment in tumor development. Curiously, the axis FKN / CX3CR1 is involved in the development of several inflammatory diseases, including obesity and diabetes are also risk factors for endometrial cancer.

A change in the expression of FKN and / or CX3CR1 is potentially capable of altering the inflammatory physiological cycle of the endometrium and therefore likely to be an element to consider in the evaluation of cancer risk factors of the endometrium.

The assumption is that the FKN / CX3CR1 couple could intervene in the pathophysiology of endometrioid adenocarcinomas.

lead_sponsor: Centre Hospitalier Universitaire de Nice


summary:
Myeloproliferative disorders (MPD) include chronic myeloid leukemia (CML) (Ph +) and essential thrombocythemia (ET), the polycythemia vera (PV), myelofibrosis (MF) called SMP Ph. CML is the ultimate model of carcinogenesis. SMP is a characterized by a malignant monoclonal proliferation of a pluripotent hematopoietic progenitor determined by the presence of a balanced translocation between chromosomes 9 and 22 (Ph chromosome) which leads to major changes of a large number of cell functions. Investigators now believe that within the bone marrow exist two types of "hematopoietic niches' niche osteoblastic / endosteal and vascular niche, controlling the maintenance and differentiation of hematopoietic stem cell pool. The endosteal niche, is a hypoxic region near the endosteal trabecular, which provides protection to deeply dormant stem cells. Data from the literature suggest that in the SMP, especially CML, the interaction of malignant stem cells with the microenvironment niche Endosteal could favor their survival and resistance to treatment. The therapeutic management of CML was upset by the use of tyrosine kinase inhibitors (TKIs). However, despite these advances, even in situations of undetectable residual disease, it has been observed relapses of the disease stopped TKI leaving suggest that there is a resistance of leukemic stem cell to TKI.

Work in the group Bipoa "Bio Engineering and Pathophysiology Osteo-Articular" helped develop a 3D model of ex vivo bone formation, which can mimic the endosteal niche. the goal is to apply this model to the SMP of hematopoiesis by referring to normal hematopoiesis. it will be tested the hypothesis that the endosteal ex vivo recess of the 3D modeling allows to highlight a special interaction can promote the persistence of the leukemia stem cell despite the use of effective therapies.


title: Plasticity and Cross-modal Interactions for Oral Communication in Profoundly Deaf Adults

acronym: PLASMODY

summary:
The aim of this study is to evaluate cerebral asymmetry for face processing in a group of profoundly deaf participants and a group of hearing controls by the mean of fMRI measure. To this end, we present chimeric faces (faces split into different halves), entire faces, or faces presented in divided visual field, and subjects perform a gender categorization task while lying in a fMRI scanner.

It is expected to find a reduced cerebral asymmetry in the Fusiform Face Area in deaf in comparison with hearing participants.


title: Post-fall Syndrome of the Aged Person : Contribution of SAFEWALKER for Rehabilitation

acronym: SAFEER

summary: The main objective of this study is to evaluate the feasibility and acceptability of the use of the robot "SAFEWALKER" complement classical rehabilitation in a group of elderly patients over 70 years during the rehabilitation of post-fall syndrome.

ReferenceCitation: Ambrose AF, Paul G, Hausdorff JM. Risk factors for falls among older adults: a review of the literature. Maturitas. 2013 May;75(1):51-61. doi: 10.1016/j.maturitas.2013.02.009. Epub 2013 Mar 22. Review.

ReferenceCitation: Büchele G, Becker C, Cameron ID, König HH, Robinovitch S, Rapp K. Predictors of serious consequences of falls in residential aged care: analysis of more than 70,000 falls from residents of Bavarian nursing homes. J Am Med Dir Assoc. 2014 Aug;15(8):559-63. doi: 10.1016/j.jamda.2014.03.015. Epub 2014 May 11.

ReferenceCitation: Cumming RG, Salkeld G, Thomas M, Szonyi G. Prospective study of the impact of fear of falling on activities of daily living, SF-36 scores, and nursing home admission. J Gerontol A Biol Sci Med Sci. 2000 May;55(5):M299-305.

ReferenceCitation: Denkinger MD, Lukas A, Nikolaus T, Hauer K. Factors associated with fear of falling and associated activity restriction in community-dwelling older adults: a systematic review. Am J Geriatr Psychiatry. 2015 Jan;23(1):72-86. doi: 10.1016/j.jagp.2014.03.002. Epub 2014 Mar 15. Review.

ReferenceCitation: Evitt CP, Quigley PA. Fear of falling in older adults: a guide to its prevalence, risk factors, and consequences. Rehabil Nurs. 2004 Nov-Dec;29(6):207-10. Review.


title: Development of New Cortical Excitability Methodologies Using Robotised and Neuronavigated Transcranial Magnetic Stimulation.

acronym: ROBEXCI

summary:
This study has two main goals :

to develop the cortcial excitbality (CE) measurement methodology using coupling between transcranial magnetic stimulation (TMS) and physiological recordings such as electroencephalography (EEG) and electromyography (EMG),
to automatize these measurements using robotized TMS.

Assessing CE is a preliminary and crucial step in any TMS protocol, in either fundamental or clinical research. It is an important indicator which determine the stimulation power applied on the cortical target during the TMS experiment, or during the rTMS cure (patients). CE is in general measured on the motor cortex using EMG activity as the main indicator of the system's response, whatever the real cortical target is located. The present study thus propose to generalize this measurement on other cortical areas in link with the actual targets, and using other external recordings such as EEG. Moreover, as neuronavigation systems significantly improved TMS precision in the past years, CE measurements could significantly gain to become fully automatized using robotized TMS.


title: Virtual Reality and Concept of Control in the Treatment of Acrophobia by Exposure to Virtual Environments: Comparative Test

acronym: CTRLSTRESS

summary: Virtual reality is currently used as a therapeutic strategy in common phobia as agoraphobia or acrophobia, since it permits to have a better control (on occurrence of events or on the environment) during the therapy than in "in vivo" therapy. Our hypothesis here is that we can improves the therapeutic effects of the virtual exposure by giving control to acrophobic patients during their exposure.

lead_sponsor: Qualissima

location_facility: Service hospitalo-universitaire de psychologie médicale de psychiatrie d'adultes du Pr Lançon - CHU Marseille


title: Evaluation and Medical Care of Oculomotor Dysfunction Leading to Vertigo in Children

acronym: VERVE

summary: The eye movements of vergence allow binocular vision whatever the viewing distance or the body movements are and the perception of depth. Vergence dysfunction can lead to erroneous visual sensation of movements. In our daily life using screens (computer, game boys..) is increasing and this approach heavily the ocular vergence and can lead to symptoms if oculomotor and accommodative systems are dysfunctioning (Ped. Neurology 2000). Not knowing this pathology lead to inappropriate and expensive prescription CT scan or NMR. To evaluate the vergence performances just evaluation in static condition is currently available in ophthalmology departments. The CNRS laboratory (IRIS, FRE 3154) adapted a technic of eye movement recording to study ocular vergence in dynamic condition.


title: A Phase 3b Open-label, Multicenter, Safety and Efficacy Extension Study of a Recombinant Coagulation Factor IX Albumin Fusion Protein (rIX-FP) in Subjects With Hemophilia B

summary:
This study will examine the long-term safety and efficacy of rIX-FP for the control and prevention of bleeding episodes in children and adults with severe hemophilia B. The study will include subjects who have not previously been treated with Factor IX products, subjects who previously completed a CSL-sponsored rIX-FP lead-in study and subjects requiring major non-emergency surgery who have not previously completed a CSL-sponsored rIX-FP lead-in study.

A surgical prophylaxis substudy will examine the efficacy of rIX-FP in subjects with hemophilia B who are undergoing non-emergency major or minor surgery. An additional substudy will examine the safety and PK of subcutaneous (SC) administration of rIX-FP.

lead_sponsor: CSL Behring

location_country:
Spain
Italy
Austria
Australia
Canada
Philippines
United States
France
Israel
Malaysia
South Africa
Japan
Germany
Bulgaria
Czechia

location_facility: UOS Gestione e Organizzazione Funzlone Hub Emofilia

location_facility: SHAT "Joan Pavel" ODD [Hemorrhagic Diathesis & Anemia]

location_facility: Hospital of the University of Pennsylvania

location_facility: Werlhof-Institute for Haemostasis and Thrombosis

location_facility: St. Marianna University, School of Medicine, Seibu Hospital

location_facility: Indiana Hemophilia & Thrombosis Center Inc.

location_facility: Medical University of Vienna, Vienna General Hospital

location_facility: IRCCS Ospedale Maggiore[Centro emofilia e Trobosi]

location_facility: The Hospital of Hyogo College of Medicine

location_facility: Department of Pediatrics, Medical University of Vienna

location_facility: Hopital Bicetre - Centre de Traitement del'Hemophilia

location_facility: Centro Malattie Emorragiche e Trombotiche Ospedale

location_facility: University of Occupational and Environmental Health


title: Graft Acute Kidney Injury: Vitamin B3 to Facilitate Renal Recovery In the Early Life of a Transplant - GABRIEL

acronym: GABRIEL

summary:
Delayed graft function occurs in more than 20% of kidney transplantations. It is an episode of post-ischemic acute kidney injury with long-term consequences on the allograft's function. Based on preclinical data and on a stage 1 clinical trial, the hypothesize is that an acquired defect in NAD+ biosynthesis is instrumental in delayed graft function and that a treatment with high doses of vitamin B3 (nicotinamide) will improve the early renal graft function.

Thus, it is planned to recruit 204 kidney allograft recipients immediately before transplantation and randomize them to either placebo or nicotinamide treatment for 3 administrations before transplantation, immediately after it and on the next day.

The efficacy of nicotinamide to foster early graft function will be evaluated by comparing the creatinine reduction ratio between the placebo and the nicotinamide treated groups.

Serum will be collected before and 2 days after transplantation and urine 2 days and 3 months after transplantation to study the relationship between biological markers of NAD+ biosynthesis and nicotinamide's effect on early kidney graft function.

location_facility: Department of Renal Transplantation - Hospital Pitié Salpétrière


title: Evaluation of Aortic Stiffness as a Prognostic Indicator of Aortic Dilatation in Patients With Bicuspid Aortic Valve (BAV) by Multimodal Imaging (MRI, Echocardiography and Ultrafast Ultrasound Imaging)

acronym: IRM-BAO

summary:
The objective is the development and validation of morphological markers informative of aortic dilatation in order to improve the precision of the risk of aneurysm of the thoracic aorta and of acute aortic syndrome for patients with bicuspid aortic valve (BAV).

The primary objective of this study is to demonstrate a correlation between the aortic local pulse wave velocity (PWV) measured with MRI and the progression of the thoracic aorta diameters measured by MRI after a follow-up of 2 years.

lead_sponsor: French Cardiology Society


title: Thymic Generation of Regulatory T Lymphocytes in Type I Diabetes Patients.

acronym: TregDiab

summary: Regulatory T lymphocytes play a major role in the protection from autoimmune pathology. Defects in immunosuppression mediated by these cells is therefore suspected to contribute to these diseases. This issue has very little been studied in humans.Regulatory T cells emigrated from the thymus will be isolated from the blood of patients and healthy controls. The repertoire of antigen-receptors will be analysed by high throughput sequencing and its diversity estimated using appropriate statistical models borrowed from ecology.

status: Withdrawn

ReferenceCitation: Ferreira C, Singh Y, Furmanski AL, Wong FS, Garden OA, Dyson J. Non-obese diabetic mice select a low-diversity repertoire of natural regulatory T cells. Proc Natl Acad Sci U S A. 2009 May 19;106(20):8320-5. doi: 10.1073/pnas.0808493106. Epub 2009 Apr 9.

ReferenceCitation: Thiault N, Darrigues J, Adoue V, Gros M, Binet B, Perals C, Leobon B, Fazilleau N, Joffre OP, Robey EA, van Meerwijk JP, Romagnoli P. Peripheral regulatory T lymphocytes recirculating to the thymus suppress the development of their precursors. Nat Immunol. 2015 Jun;16(6):628-34. doi: 10.1038/ni.3150. Epub 2015 May 4.

ReferenceCitation: Steffens CM, Al-Harthi L, Shott S, Yogev R, Landay A. Evaluation of thymopoiesis using T cell receptor excision circles (TRECs): differential correlation between adult and pediatric TRECs and naïve phenotypes. Clin Immunol. 2000 Nov;97(2):95-101.

ReferenceCitation: Calder AE, Hince MN, Dudakov JA, Chidgey AP, Boyd RL. Thymic involution: where endocrinology meets immunology. Neuroimmunomodulation. 2011;18(5):281-9. doi: 10.1159/000329496. Epub 2011 Sep 22. Review.

ReferenceCitation: Sakaguchi S, Miyara M, Costantino CM, Hafler DA. FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol. 2010 Jul;10(7):490-500. doi: 10.1038/nri2785. Epub 2010 Jun 18. Review.

ReferenceCitation: Lancaster GA, Dodd S, Williamson PR. Design and analysis of pilot studies: recommendations for good practice. J Eval Clin Pract. 2004 May;10(2):307-12.


title: A Double-Blind, Placebo-Controlled, Balanced, 4-Way, Incomplete Block Design to Evaluate the Effects of a Single Administration of SAM-531 on Sleep Electroencephalogram (EEG) and Quantitative Wake EEG (qEEG) in Healthy Subjects

summary: Primary: To evaluate the pharmacologic effect of single doses of SAM-531 on sleep EEG in healthy subjects.

lead_sponsor: Wyeth is now a wholly owned subsidiary of Pfizer


title: An Ascending Multiple-Dose Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SAM-315 Administered Orally to Healthy Young Adult and Elderly Subjects

summary:
Primary: To assess the safety and tolerability of ascending multiple oral doses of SAM-315, an investigational drug, in healthy young adult and elderly subjects.

Secondary: To assess the Pharmacokinetic and Pharmacodynamic profiles of multiple oral doses of SAM-315 in healthy young adult and elderly subjects.


title: A Randomized, Double-Blind, Placebo-Controlled, Ascending Multiple Dose Study of the Safety, Tolerability, and Pharmacokinetics of Lecozotan SR Administered Orally to Healthy Young and Elderly Subjects

summary: To assess the safety, tolerability and pharmacokinetics of single and multiple ascending oral doses of lecozotan SR in healthy young and elderly subjects.


title: Long-Term Supervised Treatment Interruption in HIV-Infected Patients Who Started Antiretroviral Treatment With CD4 Over 350/mm3 and Plasma HIV RNA Below 50 000/mL ANRS 116 Trial SALTO

summary: This trial is aimed at studying the safety of long term supervised treatment interruption in HIV infected patients with CD4 over 350/mm3 and plasma HIV RNA under 50 000/mL. Another aim of this study is to assess the immunological and virological factors associated with the duration of treatment interruption.

ReferenceCitation: Weiss L, Piketty C, Assoumou L, Didier C, Caccavelli L, Donkova-Petrini V, Levy Y, Girard PM, Burgard M, Viard JP, Rouzioux C, Costagliola D; ANRS 116 SALTO study group. Relationship between regulatory T cells and immune activation in human immunodeficiency virus-infected patients interrupting antiretroviral therapy. PLoS One. 2010 Jul 21;5(7):e11659. doi: 10.1371/journal.pone.0011659.

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

location_facility: Service d'immunologie Clinique, Höpital Européen Georges Pompidou


title: Lanreotide In Polycystic Kidney Disease Study

acronym: LIPS

summary:
LIPS study (Lanreotide In Polycystic kidney disease Study) is a prospective randomized double blind placebo controlled study. The main objective is to prove that lanreotide, a somatostatin analog, is able to reduce the glomerular filtration rate decline over 3 years by at least 30%. Cardiovascular outcomes, blood pressure, quality of life and safety are among the secondary outcomes. The study, which will include 180 ADPKD patients, is scheduled to start in early 2014.

An equal number of patients with chronic kidney disease stage 2 (90 patients with GFR 89 to 60 ml/mn/1.73 m2) and chronic kidney disease stage 3 (90 patients with GFR 59 to 30 ml/mn/1.73 m2) will be included. The primary endpoint (GFR decline) will be assessed by repeated measures, in the overall population as well as in the two GFR stratus.

lead_sponsor: Assistance Publique - Hôpitaux de Paris


title: Influence of Environmental Conditions on In Vitro Fertilization (IVF) Attempts and Induced Pregnancies

acronym: MeteoFIV

summary:
The main purpose of the study is to assess the impact of environmental conditions on live-birth rates after intraconjugal IVF.

The second purposes are

to assess the impact on pregnancies (prematurity, preeclampsia);
to assess the impact on newborn's health (stunted growth);
to evaluate the consistency of results observed between assisted pregnancies and spontaneous pregnancies.


title: Bioavailabity of the Major Metabolites of a Botanical Extract, in Healthy Adults : a Randomized, Cross-over, Open-label, Clinical Study

summary:
Scientific research on the beneficial effects of botanical extracts has led to a better understanding of the role of its bioactive compounds, but the bioavailability in human remains largely unknown. Indeed, the most of publications investigated the bioavailability of metabolites of spices in in vitro cells model or animal experiments but few clinical studies have been conducted.

Therefore, the aim of this study is to characterize and quantify in blood, the main metabolite compounds of a botanical extract, following its administration by different routes (oral or sublingual) and with different preparations (extract or powder), in quantity equivalent to those having demonstrated biological properties.

lead_sponsor: Activ'inside

location_facility: CIC Inserm 1405, University Hospital Clermont-Ferrand,


title: Phenotyping of Chronic Pain in Diffused Systemic Scleroderma: Characteristics and Perturbations of Mechanisms of Pain, Impact on the Quality of Life and Correlations of Fatigue, Sleeping Disorders and Mood or Anxiety Disorders

acronym: PAIN SSc

summary:
The primary objective of the study is to describe the different phenotyping of pain in systemic scleroderma patients and perturbations of mechanisms of the pain.

As secondary objectives, the study aims to describe the importances of overall symptoms in alteration of quality of life and conserve the questions which will be associated in a unique questionnaire in order to evaluate the pain, the fatigue and the sleeping disorders in diffused systemic scleroderma patients.

location_facility: Center of evaluation and treatment of pain - Cochin hospital - APHP


title: Behavioral Adaptation to Negative Social Cues in Depressed Patients According to Personal History of Suicide Attempt

acronym: COMPASS

summary:
Social interactions are part of daily life. To decide to interact with someone or not is a routine for humans. To ensure the quality of interpersonal relationships, emotional cues must be taken into account to adapt optimally the investigator's behavior.

Difficulties in interpersonal relationships often trigger suicidal behavior. Suicide attempters are characterized by an impaired decision - making associated with difficulties in familial relationships.

To date, little data on emotional recognition and social decision- making in clinical population is available.

The study aims to compare behavioral response to negative social cues in 82 depressed patients according to their history of suicide attempt using a computerized neuropsychological task.


title: Dosimetry and Biodistribution of [18F]-Fludarabine in Lymphoid Malignancies

acronym: FLUDATEP

summary:
The application of positron emission tomography with lymphoproliferative diseases today provides diagnostic and therapeutic information of major importance , especially in terms of speed and quality of response to treatment. The radiopharmaceutical used in clinical practice for this exam is fluorodeoxyglucose 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose ([18F]-FDG) . However , the uptake of this tracer is not elective in lymphoid tissues , with a lack of specificity. In addition , the avidity of this tracer is unequal according to the histological subtype (lack of sensitivity).

To try to improve the results of this clinical exploration of lymphoid malignancies, the investigators developed a new radiopharmaceutical ( [18F] - fludarabine ). The idea of transforming the fludarabine radiopharmaceutical is based on the existence of a fluorine atom in the molecule and the pharmacokinetic characteristics of this drug. The [18F]-Fludarabine is a new radiopharmaceutical reproducing the same dosage formulation of fludarabine , a drug used for the treatment of certain types of lymphoproliferative diseases, especially those where the tumor cells have a low proliferation kinetics . This drug is used in therapy in particular pharmacokinetic effect for a high affinity for the lymphoid tissue . Preclinical results on normal and lymphoma xenograft -bearing mice showed a specificity restricted to lymphoid tissue fixation with [18F]-Fludarabine compared with [18F]-FDG .

Based on these encouraging results , the investigators propose in this work to explore the Dosimetry and Biodistribution of [18F] - Fludarabine in human lymphoproliferative diseases : 1)A first group of patients with non-Hodgkin's large cell lymphomas in which it already has a wealth of experience in exploration [18F]-FDG, and 2) a second group of patients with chronic lymphocytic leukemia, where the results of the exploration [18F]-FDG are considered disappointing and did not, for this reason, experienced clinical development.

lead_sponsor: University Hospital, Caen


title: Cardiopulmonary Fitness and Its Clinical Determinants of a Population of Childhood Cancer Survivor: a Controlled Retrospective Study

acronym: ONCO-SPORT

summary:
Medical progress have made it possible to considerably improve the survival of children with an oncological disease. Currently, the survival rate increased to above 90 % in the most developed countries . This increase of childhood cancer survivors (CCS) asks us about their future and their quality of life. Assessing health related life quality , previous studies observe that in this particular population of patients, it is related to a poor physical capacity , physical activity level and many of these patients do not meet the activity level recommended by the world health organization due to fatigability and sedentary behaviours . In addition to these habits, the CCS are more susceptible to develop cardiovascular risk (CVR) leading to cardiovascular disease in adulthood and increases them mortality . Furthermore, CCS who have been experiencing hematopoietic stem cells transplantation (HSCT) are more susceptible to develop these CVR. In parallel with the common CVR, lower cardiopulmonary fitness assessed by cardiopulmonary exercise test (CPET) in the general population has been established as a major and independent CVR for cardiologic events.

Cardiopulmonary fitness assessed by maximal cardiopulmonary exercise test (CPET) allows physicians to measure metabolic response to maximal effort in a population that is known as VO2max. This domain of applied physiology permits a new way to approach the understanding of global health prognosis in chronic disease. For example, decrease of VO2max is involved in lower quality of life in patients with congenital heart disease. Cardiopulmonary exercise test for VO2max exploration has been demonstrated feasible in child patients with leukemia or other tumors after intensive chemotherapy, prior to HSCT.

Assessment of cardiopulmonary fitness in CCS is already described in previous studies, but this study aimed to compare a maximal CPET assessment on a large childhood cancer survivors cohort with healthy control, on a quite young cohort, during the oncologic follow up and find out its determinants.


title: Comparison of 3 Exercise Training Modalities in Obese Patient With Sleep Apnea Syndrome Treated by Continue Positive Airway Pressure : a Randomized Controlled Study

summary:
The study was designed to test the following hypotheses:

In obese patients with OSAS, the benefit of the combination of exercise training + continuous positive airway pressure (CPAP) will be higher than CPAP alone in term of functional capacity, metabolic, inflammatory, cardiovascular and sleep parameters and quality of life.

In obese patients with OSAS, the benefit of training using ventilatory assistance (NIV) during cycloergometer [cycloergometer with NIV] or respiratory muscles training (spirotiger) in addition to cycloergometer [cycloergometer + spirotiger] will be higher than cycloergometer training alone [cycloergometer] in term of functional and exercise capacities.

Dyspnea during walking test and respiratory muscle strength at baseline could influence the response to combined exercise training such as [cycloergometer + NIV] or [cycloergometer + spirotiger]

ReferenceCitation: Vivodtzev I, Tamisier R, Croteau M, Borel JC, Grangier A, Wuyam B, Lévy P, Minville C, Sériès F, Maltais F, Pépin JL. Ventilatory support or respiratory muscle training as adjuncts to exercise in obese CPAP-treated patients with obstructive sleep apnoea: a randomised controlled trial. Thorax. 2018 Feb 20. pii: thoraxjnl-2017-211152. doi: 10.1136/thoraxjnl-2017-211152. [Epub ahead of print]

lead_sponsor: AGIR à Dom

location_country: Canada France

location_facility: Institut Universitaire de Cardiologie et de Pneumologie de Quebec (IUCPQ)


title: Testing of NBIA Genes: Analysis of Genetic Heterogeneity and Validation of Mitochondrial Markers for Assessing Causality of Sequence Variants.

acronym: NBIA MITO

summary:
Neurodegeneration with brain iron accumulation (NBIA) represent a group of rare neurodevelopmental diseases, genetically as well as phenotypically heterogeneous.

The diagnosis is based on brain MRI. It is also based on genetic testing. However overlaps exist between the different clinical presentations and the molecular diagnosis may be misinterpreted.

Two main purposes must be addressed to get a better molecular diagnosis: on one hand reaching enough exhaustivity which may be performed with a larger gene panel and next generation sequencing; on the other hand, it is now necessary to validate or infirm the deleterious consequences of variants with the help of functional studies.

location_facility: Centre Hospitalier Universitaire de Bordeaux

intervention_type: Genetic


title: Prospective Cohort Primary Hyperparathyroidism

acronym: CoHPT

summary: CoHPT is a prospective, monocentric, observational cohort including all patients diagnosed with primary hyperparathyroidism in Nantes University Hospital, aiming to study the outcomes associated with parathyroidectomy. Clinical and biochemical evaluation is performed at the inclusion, and 6, 12, 36 and 60 months. A biocollection is collected. The main hypotheses are that parathyroidectomy could improve cardiovascular, renal, bone, and cardiovascular outcomes along with quality of life.

lead_sponsor: Nantes University Hospital


title: Biomarkers in Autoimmune Diseases, Vasculitis and Auto Inflammatory Diseases

acronym: BIOMAI

summary:
The objective of this work is to identify, in patients with autoimmune diseases, systemic vasculitis and autoinflammatory disease, cytokine and lymphocyte biomarkers of activity of these diseases to identify follow-up biomarkers, in order to personalize the follow-up and the treatments for each patient.

Immunological data will be obtained from biological samples collected as part of the usual patient care pathway (Blood and tissues sampling) The study will take place in the Department of Internal Medicine and Clinical Immunology (DMIIC), that is certified as the National Reference Centre for Rare Systemic Autoimmune Diseases and the National Reference Centre for Inflammatory Autoinflammatory Diseases and Inflammatory Amyloidosis (CEREMAIA). Its objective is to contribute to the advancement of fundamental knowledge in immunology, in particular to develop prognostic biomarkers of the activity of autoimmune diseases, systemic vasculitis and autoinflammatory diseases by using blood tests.

location_facility: Département de Médecine Interne et Immunologie Clinique (DMIIC), Hôpital Pitié-Salpêtrière


title: Effect of Intrapulmonary Percussion Ventilation on Deposition of Inhaled Aerosols in Idiopathic Pulmonary Fibrosis

acronym: AEROPERC

summary:
This protocol aims to evaluate the feasibility and benefit of Intrapulmonary Percussive Ventilation (IPV) to improve deposition of inhaled radiolabelled aerosols in fibrotic lung regions of patients with Idiopathic Pulmonary Fibrosis (IPF).

Phase 1 of the protocol aims to identify the highest IPV pressure that is tolerated by individual patients. Secondary endpoints explore safety of IPV in IPF patients.

Phase 2 of the protocol is a crossover randomized trial where patients will inhale 99mTc-labelled DiethyleneTriamine PentaAcetate (DTPA) aerosols with or without IPV. Aerosol deposition in HRCT-defined fibrotic regions of interest (ROI) is described by Single Photon Emission Computed Tomography (SPECT).

lead_sponsor: University Hospital, Tours

location_facility: Pulmonology Department, University Hospital, Tours

intervention_type: Radiation


title: Recovery Optimisation in Emergency Medicine Addressing Stress Adaptation Techniques

acronym: REST

summary:
The investigators hypothesize that a recovery management program could have an impact on emergency nurses and physicians by improving their sleep and reducing their psychological and physiological responses when dealing with stressful situations during their professional practice. The REST study consists in developing a recovery management program for emergency professionals. The following strategies would be proposed :

sleep management according to their schedules by anticipation and recovery,
stress management through cardio-feedback techniques (cardiac coherence) also called controlled breathing techniques and mental imagery.

The objectives are to evaluate the impact of this program on the physiological and psychological stress of the emergency professionals during their professional activity, as well as on their sleep. To do so, their respiratory and heart rates, as well as their activity and resting times will be recorded continuously for one week. At the end of each shift, the emergency professionals will report and evaluate the 3 most stressful events.

primary_purpose: Health Services Research

lead_sponsor: Hospices Civils de Lyon


title: Neopterin on Admission to the ICU: an Immunological Biomarker That Could Help Admission Decisions by Identifying Elderly Patients (≥80 Years) Able to Survive an ICU Stay Without Disability

acronym: NUAGE

summary:
For the last twenty years, the proportion of patients aged 80 years and more, hospitalized in intensive care (ICU) has been increasing. The question of the admission of an elderly patient in intensive care raises many medico-socio-economic questions. The general objective of geriatric management is to improve the survival of the patient by maintaining his autonomy. Before an invasive management, it is therefore important to assess which patients are capable of surviving in good conditions. Moreover, as intensive care resources are not extensible, it is important to rationalise the use of this type of care. To date, there are no reliable criteria for predicting which patients will benefit from ICU care. The use of a predictive biomarker, in addition to the existing scores which are not very effective in this population, could guide the intensive care physician in his decision which is generally made in the emergency.

The hypothesis of the study is that neopterin measured on admission of the elderly patient to the ICU may improve prediction of survival without major loss of autonomy at 3 months. Acute stress induced by a serious pathology has a profound impact on the immune system via the activation of the neuroendocrine system and the production of endogenous cortisol. Usually, cortisol inhibits the production of pro-inflammatory cytokines such as interferon gamma (IFNg). Sometimes this inhibition is ineffective and leads to an intense pro-inflammatory state that is harmful to the body. Neopterin is produced by monocytes/macrophages under the influence of IFNg. It is associated with a poor prognosis in many diseases such as sepsis or cancer. In the comorbid elderly patient with an upper femoral fracture, the pre-operative neopterin level is predictive of one-year mortality and functional recovery.

The hypothesis of the study is that neopterin measured on admission of the elderly patient to the ICU may improve prediction of survival without major loss of autonomy at 3 months.

Each patient will be included on admission to the intensive care unit within a maximum of 24 hours (D0). Demographic data (age, sex), severity (IGSIII), comorbidity (CIRS), autonomy (ADL and IADL) and frailty (CFS) scores will be collected as well as the diagnosis at admission.

Two additional tubes will be collected during the entry assessment (performed as part of usual care) at inclusion (D0) for neopterin and other biomarkers (4 ml dry tube and 10 ml lithium heparin tube). The blood tubes will be transferred to the research laboratory within 48 hours after sampling. The determination of neopterin, cytokines and oxidative stress biomarkers will be performed by an enzyme-linked immunosorbent assay (Neopterin ELISA Kit CE-IVD, Tecan laboratory) at the Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris).

The assays will be performed at the end of the study, blinded to the patient's outcome, and the follow-up of the patients will be performed blinded to the results of the neopterin assay and the other markers.

Patients will be followed up at 3 months from inclusion (M3). The follow-up data will be collected during a routine geriatric consultation. During this consultation, the scores of comorbidities (CIRS), autonomy (ADL and IADL) and frailty (CFS) will be collected. An assessment of physical performance will be carried out by measuring the Short Physical Performance Battery (SPPBS) and the "Handgrip". If it is impossible to carry out the consultation (patient unable to move), the follow-up data (CIRS, ADL and CFS) will be collected from the patient or his relatives during a phone interview conducted by a clinical research technician.

location_facility: Hôpital Saint-Antoine / Service de réanimation


title: Sexuality and Sexual Quality of Life in Adult Patients With Turner Syndrome (TS) Compared With Patients With Primary Ovarian Insufficiency and Normal Karyotype

acronym: SEXATURN

summary:
Turner syndrome (TS) is a rare disease affecting 1/2500 female. It is defined by a complete or partial loss of an X chromosome associated with clinical signs. The most frequent signs are a small height and primary ovarian insufficiency (POI). POI occurs in 95% of patients with TS. Clinically, patients have amenorrhea with elevated FSH levels (> 25 IU/L), before the age of 40. In most cases, patients receive hormonal replacement therapy. Among patients with POI, TS is present in less than 10% of cases. Therefore POI may occur in patients with normal karyotype, therefore without TS.

Preliminary data suggest altered sexual function in patients with TS. The first goal of our study is to evaluate sexual function and sexual quality in patients with TS using a questionnaire, the Female Sexual Function Index (FSFI).

The second goal is to compare sexual quality in patients in patients with TS compared to female patients with POI not related to TS. Our study should identify predictive markers of altered sexual function.

The final endpoint is to optimize the quality of life of patients with TS and to enhance, if necessary psychological support in such patients.

status: Enrolling by invitation

location_facility: Hôpital St Antoine, Sorbonne University, Endocrinology-Diabetology Department, Reproductive medicine


title: Rituximab in Patients With ST-elevation Myocardial Infarction: A Phase 2 Placebo-controlled Randomized Clinical Trial: RITA-MI 2

summary:
The main objective is to compare the effect of a single injection of two doses of rituximab versus placebo on 6 months left ventricular systolic function, using CMR, in patients who have had an acute anterior STEMI.

The primary endpoint is the left ventricular ejection fraction (LVEF) by CMR at 6 months.

location_facility: Cardiology department, Hôpital Bichat, AP-HP


title: Differential Vulnerability of Individual Thalamic Nuclei: Toward New Biomarkers in Multiple Sclerosis

acronym: THALNUC-MS

summary: The thalamus is composed of several nuclei interlocked in a complex anatomy. In multiple sclerosis (MS), the thalamus can be altered due to disconnection by white matter lesions and due to direct damages that could be partly mediated by CSF. Due to such pathophysiology and complex anatomy, some nuclei could be more vulnerable to multiple sclerosis than others. We will test this hypothesis by using a new algorithm to automatically segment several nuclei that we will be applied to the French national MS database


title: Involvement of Polymorphonuclear Neutrophils and Platelets in Severe Form of COVID-19

acronym: NeutroVID

summary: The main objective is to quantify the population of reverse migrating neutrophils in patients with COVID-19.

location_facility: Intensive care department, Hôpital Saint Antoine


title: Set up a Community Online in a Virtual Community Game for Tobacco Prevention in Teenagers

acronym: SCOTT

summary:
The main objective of the SCOTT project is to reduce tobacco experimentation of teenagers through an online intervention based on social networking and empowerment of users.

Specific objectives of this emerging project are : 1. To develop or identify an online community dedicated to teenagers where the investigators will develop anti-smoking skills and norms. It will be based on social cognitive theory and will combine multiple functionalities based on the current practices and preferences of adolescents on internet and mobile; ensuring user safety, regulatory and ethical issues ; 2. To analyse the adoption, acceptance and the usability of SCOTT among users in a limited scale 3.To develop SCOTT process and impact assessment methodology.

Research hypothesis Providing access to prevention in an online community will: 1) Strengthen anti-smoking skills 2) Enhance the empowerment of users 3) Allow the implementation of health interventions 4) Improve indicators of tobacco consumption in young people Methods The overall methodology of the project relies on a multidisciplinary approach with a consortium of French experts in public health (health promotion and epidemiology), education science, information and communication technologies, medical informatics, adolescent medicine, adolescent addictology, social sciences, ethics and law. The project will be led in 3 parts: 1) Development of the intervention - using the Integrate, Design, Assess, and Share (IDEAS) framework. Using qualitative methods (individual interview, focus groups), multidisciplinary team brainstorming, works meeting and quantitative assessment of SCOTT quality; the investigators will (a) empathize with target users, (b) specify target behavior, (c) ground in behavioral theory, (d) ideate implementation strategies, (e) prototype potential products, (f) gather user feedback, (g) build a minimum viable product, 2) Pilot study : (h) SCOTT will be deploying on a small scale to assess its usability; 3) Development of the large-scale evaluation protocol - following the recommendations of the Medical Research Council concerning the evaluation of complex interventions. The investigators will (i) develop, based on the results of the pilot test, the SCOTT process evaluation methodology, (j) develop the SCOTT impact / effectiveness evaluation methodology.


title: Detection of Subclinical Cerebral Suffering Related to Hypertension Using Multimodal MRI (SOUCHY) Brain Changes Due to Hypertension: a Multimodal MRI

acronym: SOUCHY

summary: Investigators propose here to study the brain consequences of hypertension in patients without cognitive complaints and neurological signs. The evaluation of brain suffering requires considering various possible brain damage. The team developed a multimodal MRI approach capable of detecting and quantifying numerous indices (e.g. morphometric, microstructural) to evaluate possible brain suffering. This project aims to identify individually signs of cerebral suffering in hypertensive patients compared to a population of normotensive volunteers, using advanced multiparametric MRI methods.


title: Postoperative Painful Chronicization After Knee Replacement Surgery : Exploratory Study of BDNF's Kinetics

acronym: KNEE BDNF

summary:
Chronic pain is an extremely disabling disease. It is a major public health problem due to the lack of effective therapy.

Chronic postoperative pain (CPOP) is defined by a painful symptomatology in the operated area unrelated to previous pain, present for more than 3 months, and without any link to surgical complication.

The prevalence of chronicization of postoperative pain is 30% after total knee arthroplasty.

Identification of clinical, biological and psychological profiles are crucial to prevent CPOP.

A biologic factor, Brain Derived Neurotrophic Factor (BDNF) produced by a variety of cells is a key regulator of neuroplasticity. BDNF is increasingly studied in the mechanisms of cerebral sensitization and pain chronicization. The role of BDNF in pain of patients remains to be explored in a prospective study. The aim of this observational study is to compare the kinetics of BDNF after total knee arthroplasty in patients with and without CPOP.

Patients will be included in the study at the preanesthetic consultation. Serum BDNF levels will be measured preoperatively, 48h postoperatively, 3 and 6 months after surgery.

location_facility: Department of Anesthesiology and critical care, Lapeyronie University Hospital


title: Use of "BUBOLight®" Device as an Innovative Phototherapy Device for the Treatment of Newborn's Jaundice. A Monocentric, Descriptive Pilot Study, for the Feasibility, Safety and Tolerance of the BUBOLight® Device

acronym: BUBO

summary:
About 50% of full-term newborns and 80% of premature infants develop jaundice which is due to hyperbilirubinemia. In the majority of cases, jaundice disappears naturally without treatment within three weeks of birth, but the bilirubin level may remain too high, which can lead to a serious neurological disease: kernicterus. To avoid this, a therapeutic management must be instituted, and in some cases, one or more phototherapy sessions (PT) may be prescribed.

The aim of this trial is to evaluate the safety and level of satisfaction of parents and healthcare team with one innovative device for phototherapy BUBOLight® included two removable strips of luminous textile incorporating optical fibers.

10 newborns requiring phototherapy, will be illuminated during four hours in one session of PT Bilirubin levels is taken at the start of phototherapy H0 and Controls are made at H+6 hours.

ReferenceCitation: Lecomte F, Thecua E, Ziane L, Deleporte P, Duhamel A, Vamour C, Mordon S, Rakza T. Phototherapy Using a Light-Emitting Fabric (BUBOLight) Device in the Treatment of Newborn Jaundice: Protocol for an Interventional Feasibility and Safety Study. JMIR Res Protoc. 2021 May 25;10(5):e24808. doi: 10.2196/24808.

lead_sponsor: University Hospital, Lille


title: Qualitative Study of the Experience of Adolescents and Health Professionals Faced With the Necessity for Changing to Remote Care During the COVID-19 Outbreak Quarantine

summary: The Maison des Adolescents (MDA) at Cochin Hospital (Paris) is a multidisciplinary service which welcomes adolescents in three different units: consultation, day care and hospitalization. However, the epidemic of coronavirus (COVID-19) in March 2020 which imposed the extreme limitation of contacts and then the confinement of the entire population, required urgent adaptation of care practices. Teleconsultation quickly became essential for most consultations (psychiatrists, psychologists, nurses, but also pediatricians and somatic physicians). In day hospital, daily reception could not be carried out, therapeutic workshops, family interviews, or speaking groups were organized remotely. In hospital unit, the interruption of visits required the organization of remote interviews with families. Far from the comfort of an organized and structured telepsychiatry, the use of videoconferencing was done in an emergency and without preparation. The objective is to explore the experience of adolescents, doctors and psychologists regarding emergency changes in the methods of their follow-up by setting up teleconsultation in the context of the COVID-19 epidemic.

lead_sponsor: Hôpital Cochin


title: Ultrasonographic and MRI Explorations of Infraspinatus Muscle in Postero-superior Rotator Cuff Tear

acronym: VISUMIR

summary: The project aims to evaluate the contribution of texture analysis on MRI sections, and the technical feasibility, reproducibility, and clinical relevance of quantitative ultrasound and elastography to characterize the composition and volume of infraspinatus muscle in postero-superior rotator cuff tears. The perspectives are to optimize the imaging to allow a quantitative, objective and reproducible analysis of the muscle tissue and its characteristics.


title: Impact of a Mobile Geriatric Team With a Pharmacist on the Optimisation of Prescriptions in Elderly Inpatients

acronym: PHARMOG

summary: In patients aged 75 years and older, polypathology is frequent and often associated with polypharmacy. This polypharmacy coupled with a lack of proactive elderly care can sometimes lead to hospitalisation. Due to comorbidities and complex problems, management of geriatric patients usually requires a multidisciplinary approach. In Toulouse University Hospital, elderly inpatients can benefit from a geriatric assessment by a Geriatric Mobile Team. Whether this team improve the prescriptions through the advice of a clinical pharmacist has not been demonstrated yet.

ReferenceCitation: Pagès A, Roland C, Qassemi S, Abdeljalil AB, Houles M, Romain M, Toulza O, Belloc A, McCambridge C, Voisin T, Cestac P, Juillard-Condat B; PharMoG study group. Impact of a Pharmacist-included Mobile Geriatrics team intervention on potentially inappropriate drug prescribing: protocol for a prospective feasibility study (PharMoG study). BMJ Open. 2020 Dec 2;10(12):e040917. doi: 10.1136/bmjopen-2020-040917.

lead_sponsor: University Hospital, Toulouse


title: Phenotypic and Functional Characterisation of Human B-cell Response in Pemphigus and Application to Other Auto-immune Diseases

acronym: CaReLyBP

summary: Pemphigus is a rare autoimmune disease involving skin and mucous membranes characterized by the production of pathogenic autoantibodies directed against desmosomal transmembrane glycoproteins belonging to the cadherin family,responsible for the disruption of desmosomes leading to the acantholysis phenomenon.Two main classical subtypes of pemphigus have been individualized:pemphigus vulgaris and foliaceus,in which pathogenic autoantibodies are directed against desmoglein 3 and 1 respectively.The knowledge about B-cell populations responsible for pemphigus activity increased a lot.In pemphigus patients,B-cell population was shown to comprise auto-reactive B lymphocytes producing antibodies targeting desmogleins,directly responsible for disease activity,and regulatory B lymphocytes.After rituximab treatment,clinical activity was proved to be associated with circulating auto-antibodies high titers and an increase of auto-reactive B-cells,whereas clinical remission was associated with a change in B-cell populations,as B cell repertoire changed from oligoclonal to polyclonal when reconstituting after treatment,with an increase of immatures and transitional B-cells producing IL-10.The mechanisms leading to autoreactive B-cells appearance,the precise role of B-reg in immune tolerance and the factors triggering the imbalance between pro autoimmune and regulatory immune B-cells leading to pemphigus activity remain to be discovered.Polymorphonuclear neutrophil granulocytes(PMN) are the first responders of the immune system to threats by invading microorganisms.Since 2004, PMN were shown to produce neutrophil extracellular traps(NET),structures consisting of decondensed chromatin embedded with histones,granular and cytoplasmic proteins that trap and kill microbes.In lupus recent works demonstrated evidences that NETs components are found in immune complexes responsible for tissue inflammation and that polyclonal activation of B-cell as well as memory B-cell activation could be obtain in presence of immune complexes derived from NET.Besides lupus,other works showed evidence of NETs implication in inflammatory and auto-immune states in rheumatoid arthritis and small vessel vasculitis.The hypotheses is that B-cell activation by NET might not be restricted to autoimmune diseases of which antibodies target NETs components.The aim is to assess the effects on B-cell activation and the phenotypic changes in B-cell population from pemphigus patients after stimulation by NET.

ReferenceCitation: Langan SM, Smeeth L, Hubbard R, Fleming KM, Smith CJ, West J. Bullous pemphigoid and pemphigus vulgaris--incidence and mortality in the UK: population based cohort study. BMJ. 2008 Jul 9;337:a180. doi: 10.1136/bmj.a180.

ReferenceCitation: Hashimoto T, Amagai M, Garrod DR, Nishikawa T. Immunofluorescence and immunoblot studies on the reactivity of pemphigus vulgaris and pemphigus foliaceus sera with desmoglein 3 and desmoglein 1. Epithelial Cell Biol. 1995;4(2):63-9.

ReferenceCitation: Martel P, Joly P. Pemphigus: autoimmune diseases of keratinocyte's adhesion molecules. Clin Dermatol. 2001 Nov-Dec;19(6):662-74. Review.

ReferenceCitation: Amagai M, Tsunoda K, Zillikens D, Nagai T, Nishikawa T. The clinical phenotype of pemphigus is defined by the anti-desmoglein autoantibody profile. J Am Acad Dermatol. 1999 Feb;40(2 Pt 1):167-70.

ReferenceCitation: Mahoney MG, Wang Z, Rothenberger K, Koch PJ, Amagai M, Stanley JR. Explanations for the clinical and microscopic localization of lesions in pemphigus foliaceus and vulgaris. J Clin Invest. 1999 Feb;103(4):461-8.


title: Interaction of HIV/Platelets and HIV-platelets/Lymphocytes in HIV Patients Under cART Treatment But Immunological Non Responders

acronym: PLAQUEVIH

summary:
The investigators propose that the lack of immune response in InR is driven by HIV-containing platelets that might interact with macrophages and CD4+ T-cells although by different mechanisms. In the one hand, HIV-sheltering platelets might fuel tissue HIV macrophage and in turn T cell reservoirs as observed in InRs and/or maintain a low-level viral replication in macrophages, sustaining a persistent inflammatory profile on in these cells. In the other hand,HIV-sheltering platelets might induce CD4+ T-cells dysfunctions via platelets/ectosomes, although without promoting platelet-to-T-cell HIV transfer/infection, thereby increasing the number of peripheral inflammatory TH17 cells and a TH17/Treg unbalance as observed in InRs.

Main Objectives:

i) To characterize and the molecular and functional level the platelet factors implicated in HIV transfer to tissue-like macrophages as well as in the immunomodulatory activity of HIV-containing platelets on macrophages and CD4+ T-cells.

ii) To interrogate the transfer of HIV-containing platelet-derived mRNA and microRNA to tissue-like macrophages and CD4+ T-cells as one major mechanism of target cell immunomodulation.

iii) To investigate the therapeutic potential of anti-platelet aggregation/activation agents (e.g. Abciximab), known to block platelet-immune cell interaction, in improving immune cell functions in vitro and promoting immunological recovery in vivo.

ReferenceCitation: Ganor Y, Real F, Sennepin A, Dutertre CA, Prevedel L, Xu L, Tudor D, Charmeteau B, Couedel-Courteille A, Marion S, Zenak AR, Jourdain JP, Zhou Z, Schmitt A, Capron C, Eugenin EA, Cheynier R, Revol M, Cristofari S, Hosmalin A, Bomsel M. HIV-1 reservoirs in urethral macrophages of patients under suppressive antiretroviral therapy. Nat Microbiol. 2019 Apr;4(4):633-644. doi: 10.1038/s41564-018-0335-z. Epub 2019 Feb 4.

ReferenceCitation: Real F, Sennepin A, Ganor Y, Schmitt A, Bomsel M. Live Imaging of HIV-1 Transfer across T Cell Virological Synapse to Epithelial Cells that Promotes Stromal Macrophage Infection. Cell Rep. 2018 May 8;23(6):1794-1805. doi: 10.1016/j.celrep.2018.04.028.

ReferenceCitation: Kaufmann GR, Perrin L, Pantaleo G, Opravil M, Furrer H, Telenti A, Hirschel B, Ledergerber B, Vernazza P, Bernasconi E, Rickenbach M, Egger M, Battegay M; Swiss HIV Cohort Study Group. CD4 T-lymphocyte recovery in individuals with advanced HIV-1 infection receiving potent antiretroviral therapy for 4 years: the Swiss HIV Cohort Study. Arch Intern Med. 2003 Oct 13;163(18):2187-95.

ReferenceCitation: Baker JV, Peng G, Rapkin J, Krason D, Reilly C, Cavert WP, Abrams DI, MacArthur RD, Henry K, Neaton JD; Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA). Poor initial CD4+ recovery with antiretroviral therapy prolongs immune depletion and increases risk for AIDS and non-AIDS diseases. J Acquir Immune Defic Syndr. 2008 Aug 15;48(5):541-6. doi: 10.1097/QAI.0b013e31817bebb3.

ReferenceCitation: Kelley CF, Kitchen CM, Hunt PW, Rodriguez B, Hecht FM, Kitahata M, Crane HM, Willig J, Mugavero M, Saag M, Martin JN, Deeks SG. Incomplete peripheral CD4+ cell count restoration in HIV-infected patients receiving long-term antiretroviral treatment. Clin Infect Dis. 2009 Mar 15;48(6):787-94. doi: 10.1086/597093.

ReferenceCitation: Chêne G, Sterne JA, May M, Costagliola D, Ledergerber B, Phillips AN, Dabis F, Lundgren J, D'Arminio Monforte A, de Wolf F, Hogg R, Reiss P, Justice A, Leport C, Staszewski S, Gill J, Fatkenheuer G, Egger ME; Antiretroviral Therapy Cohort Collaboration. Prognostic importance of initial response in HIV-1 infected patients starting potent antiretroviral therapy: analysis of prospective studies. Lancet. 2003 Aug 30;362(9385):679-86.

ReferenceCitation: Deeks SG, Kitchen CM, Liu L, Guo H, Gascon R, Narváez AB, Hunt P, Martin JN, Kahn JO, Levy J, McGrath MS, Hecht FM. Immune activation set point during early HIV infection predicts subsequent CD4+ T-cell changes independent of viral load. Blood. 2004 Aug 15;104(4):942-7. Epub 2004 Apr 29.

ReferenceCitation: Hunt PW, Martin JN, Sinclair E, Bredt B, Hagos E, Lampiris H, Deeks SG. T cell activation is associated with lower CD4+ T cell gains in human immunodeficiency virus-infected patients with sustained viral suppression during antiretroviral therapy. J Infect Dis. 2003 May 15;187(10):1534-43. Epub 2003 Apr 23.

ReferenceCitation: Marziali M, De Santis W, Carello R, Leti W, Esposito A, Isgrò A, Fimiani C, Sirianni MC, Mezzaroma I, Aiuti F. T-cell homeostasis alteration in HIV-1 infected subjects with low CD4 T-cell count despite undetectable virus load during HAART. AIDS. 2006 Oct 24;20(16):2033-41.

ReferenceCitation: Nunes-Alves C, Nobrega C, Behar SM, Correia-Neves M. Tolerance has its limits: how the thymus copes with infection. Trends Immunol. 2013 Oct;34(10):502-10. doi: 10.1016/j.it.2013.06.004. Epub 2013 Jul 16. Review.

ReferenceCitation: Wilson EM, Singh A, Hullsiek KH, Gibson D, Henry WK, Lichtenstein K, Önen NF, Kojic E, Patel P, Brooks JT, Sereti I, Baker JV; Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN Study) Investigators. Monocyte-activation phenotypes are associated with biomarkers of inflammation and coagulation in chronic HIV infection. J Infect Dis. 2014 Nov 1;210(9):1396-406. doi: 10.1093/infdis/jiu275. Epub 2014 May 9.

ReferenceCitation: Ballem PJ, Belzberg A, Devine DV, Lyster D, Spruston B, Chambers H, Doubroff P, Mikulash K. Kinetic studies of the mechanism of thrombocytopenia in patients with human immunodeficiency virus infection. N Engl J Med. 1992 Dec 17;327(25):1779-84.

ReferenceCitation: Grozovsky R, Hoffmeister KM, Falet H. Novel clearance mechanisms of platelets. Curr Opin Hematol. 2010 Nov;17(6):585-9. doi: 10.1097/MOH.0b013e32833e7561. Review.

ReferenceCitation: Hatano H, Hayes TL, Dahl V, Sinclair E, Lee TH, Hoh R, Lampiris H, Hunt PW, Palmer S, McCune JM, Martin JN, Busch MP, Shacklett BL, Deeks SG. A randomized, controlled trial of raltegravir intensification in antiretroviral-treated, HIV-infected patients with a suboptimal CD4+ T cell response. J Infect Dis. 2011 Apr 1;203(7):960-8. doi: 10.1093/infdis/jiq138.

ReferenceCitation: Green SA, Smith M, Hasley RB, Stephany D, Harned A, Nagashima K, Abdullah S, Pittaluga S, Imamichi T, Qin J, Rupert A, Ober A, Lane HC, Catalfamo M. Activated platelet-T-cell conjugates in peripheral blood of patients with HIV infection: coupling coagulation/inflammation and T cells. AIDS. 2015 Jul 17;29(11):1297-308. doi: 10.1097/QAD.0000000000000701.

ReferenceCitation: Starossom SC, Veremeyko T, Yung AW, Dukhinova M, Au C, Lau AY, Weiner HL, Ponomarev ED. Platelets Play Differential Role During the Initiation and Progression of Autoimmune Neuroinflammation. Circ Res. 2015 Oct 9;117(9):779-92. doi: 10.1161/CIRCRESAHA.115.306847. Epub 2015 Aug 20.

ReferenceCitation: Miossec P, Kolls JK. Targeting IL-17 and TH17 cells in chronic inflammation. Nat Rev Drug Discov. 2012 Oct;11(10):763-76. doi: 10.1038/nrd3794. Review.

ReferenceCitation: Rodríguez-Muñoz A, Martínez-Hernández R, Ramos-Leví AM, Serrano-Somavilla A, González-Amaro R, Sánchez-Madrid F, de la Fuente H, Marazuela M. Circulating Microvesicles Regulate Treg and Th17 Differentiation in Human Autoimmune Thyroid Disorders. J Clin Endocrinol Metab. 2015 Dec;100(12):E1531-9. doi: 10.1210/jc.2015-3146. Epub 2015 Oct 19.

ReferenceCitation: De Benedetto I, Masetti M, Fabbiani M, Biasin M, Muscatello A, Squillace N, Clerici M, Trabattoni D, Gori A, Bandera A. Higher Levels of Peripheral Th17 T CD4+ Cells Are Associated With Immunological Non Response in HIV-Infected Patients Under Effective ART. J Acquir Immune Defic Syndr. 2018 Apr 15;77(5):e45-e47. doi: 10.1097/QAI.0000000000001627.

ReferenceCitation: Deeks SG. HIV infection, inflammation, immunosenescence, and aging. Annu Rev Med. 2011;62:141-55. doi: 10.1146/annurev-med-042909-093756. Review.

ReferenceCitation: Joosse SA, Pantel K. Tumor-Educated Platelets as Liquid Biopsy in Cancer Patients. Cancer Cell. 2015 Nov 9;28(5):552-554. doi: 10.1016/j.ccell.2015.10.007.

ReferenceCitation: Laffont B, Corduan A, Plé H, Duchez AC, Cloutier N, Boilard E, Provost P. Activated platelets can deliver mRNA regulatory Ago2•microRNA complexes to endothelial cells via microparticles. Blood. 2013 Jul 11;122(2):253-61. doi: 10.1182/blood-2013-03-492801. Epub 2013 May 7.

ReferenceCitation: Risitano A, Beaulieu LM, Vitseva O, Freedman JE. Platelets and platelet-like particles mediate intercellular RNA transfer. Blood. 2012 Jun 28;119(26):6288-95. doi: 10.1182/blood-2011-12-396440. Epub 2012 May 17.

ReferenceCitation: Mann M, Mehta A, Zhao JL, Lee K, Marinov GK, Garcia-Flores Y, Lu LF, Rudensky AY, Baltimore D. An NF-κB-microRNA regulatory network tunes macrophage inflammatory responses. Nat Commun. 2017 Oct 11;8(1):851. doi: 10.1038/s41467-017-00972-z. Erratum in: Nat Commun. 2018 Aug 16;9(1):3338.

ReferenceCitation: Rowley JW, Chappaz S, Corduan A, Chong MM, Campbell R, Khoury A, Manne BK, Wurtzel JG, Michael JV, Goldfinger LE, Mumaw MM, Nieman MT, Kile BT, Provost P, Weyrich AS. Dicer1-mediated miRNA processing shapes the mRNA profile and function of murine platelets. Blood. 2016 Apr 7;127(14):1743-51. doi: 10.1182/blood-2015-07-661371. Epub 2016 Jan 14.

ReferenceCitation: Du C, Liu C, Kang J, Zhao G, Ye Z, Huang S, Li Z, Wu Z, Pei G. MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis. Nat Immunol. 2009 Dec;10(12):1252-9. doi: 10.1038/ni.1798. Epub 2009 Oct 18. Erratum in: Nat Immunol. 2010 Jun;11(6):543.

ReferenceCitation: Plé H, Landry P, Benham A, Coarfa C, Gunaratne PH, Provost P. The repertoire and features of human platelet microRNAs. PLoS One. 2012;7(12):e50746. doi: 10.1371/journal.pone.0050746. Epub 2012 Dec 4.

ReferenceCitation: Podshivalova K, Salomon DR. MicroRNA regulation of T-lymphocyte immunity: modulation of molecular networks responsible for T-cell activation, differentiation, and development. Crit Rev Immunol. 2013;33(5):435-76. Review.

ReferenceCitation: Fink L, Hölschermann H, Kwapiszewska G, Muyal JP, Lengemann B, Bohle RM, Santoso S. Characterization of platelet-specific mRNA by real-time PCR after laser-assisted microdissection. Thromb Haemost. 2003 Oct;90(4):749-56.

location_facility: Service Hématologie Immunologie, Hôpital Ambroise Paré