Saint-jean-d'angély, France

Bright Light Therapy During Residential Alcohol Withdrawal

All eligible patients will be offered and explained the study by a psychiatrist/addictologist during the consultation (or teleconsultation) to schedule a 14-day hospitalization for alcohol withdrawal (maximum 3 months before hospitalization). Patients will be randomized centrally to one of the following two treatment conditions (blind maintained by a nurse independent of the assessment), on day D0 of inpatient treatment for withdrawal (standardized withdrawal over 14 days with hydration, vitamin B1, benzodiazepines in gradual decrease before stopping and according to signs of withdrawal): 1. Active light therapy (10,000 Lux). 2. Placebo light therapy (with filter <10 Lux). Every morning in the room (patient in a single room), at 8 am, for 30 min, for the entire duration of withdrawal, i.e. 13 days (start on D1) and stopped on D14. No change in usual care apart from this intervention. After checking the inclusion and non-inclusion criteria and obtaining consent, patients will be randomized (ratio 1:1) between the groups with active light therapy or placebo, by connecting to a randomization website (REDCap software) using a randomization list prepared in advance, balanced by block of randomly variable size

Evaluation of Long-term Immunogenicity of a Boost Dose of MVA-BN Vaccine

Mpox is an endemic zoonosis in Africa, caused by the MPXV virus of which there are two clades: I (former Congo Basin) and II (former West Africa). Since 2022, clade II has emerged globally via sexual transmission, primarily among men who have sex with men (MSM), resulting in a declaration of public health emergency (PHEIC) by the WHO. In 2023, a clade I epidemic emerged in East Africa with a high case fatality rate (3-5%). In August 2024, the WHO again declared a PHEIC after the spread of clade I to African countries with no previously reported cases and outside Africa, raising fears of higher mortality and transmission. A 3rd generation vaccine, MVA-BN (Imvanex® /Jynneos®), initially developed against smallpox, was approved in 2022 to prevent mpox. In France, the HAS recommends post- and pre-exposure vaccination for populations at risk: MSM, trans people with multiple partners, sex workers and certain professionals. For people born before 1980 (history of smallpox vaccination), a single dose is recommended as primary vaccination, while immunocompromised subjects require 3 doses. Data show vaccine effectiveness of 20-80% in post-exposure prophylaxis (PEP) and ~80% in pre-exposure but neutralizing antibodies become undetectable after one year. Since the summer of 2024, the HAS has recommended a booster dose 2 years after the primary vaccination, on the basis of immunogenicity studies showing an increase in seroconversion to 98.7% one month after administration, but underlines the need to have other data, in particular on the durability of this response. A study is proposed in MSM on HIV PrEP (pre-exposure prophylaxis), a priority population for structured medical monitoring, to evaluate the immunogenicity and safety of the MVA-BN booster in this context.

Evaluation of the Efficacy of Therapeutic Infiltrations of the Pudendal Nerve, Performed Under Neurostimulation on Pain, 1 Month After an Infiltration of Local Anaesthetic, in the Treatment of Pudendal Neuralgia.

Like carpal tunnel syndrome, pudendal neuralgia (PN) is defined as a syndrome of chronic nerve compression (of the pudendal nerve) causing neuropathic pain. Treatment of NP is based on 3 therapeutic strategies of increasing aggressiveness: drug treatment, infiltrations and decompressive surgery. Drug treatment is based on the "empirical" use of drugs for neuropathic pain that have proved effective in other areas (shingles, diabetes, etc.). People with this disease are generally considered 'non-responders' to drug treatment after failure (decrease in VAS scale < 3) of at least one antidepressant and one antiepileptic drug, whose doses have been increased to the maximum possible level, or in whom a side effect has prevented the dose from being increased to the maximum authorised level. For pudendal nerve infiltration (ITNP), there is no consensus or recommendation on which molecules to use. Most studies have used a combination of local anaesthetics and corticosteroids. However, a randomised controlled trial, researchers compare lidocaine infiltration with or without methylprednisolone. The results were not significantly different (14% vs 11%). According to the data in the literature, less than half of patients (11% to 39%) are relieved in the short term, up to 3 months, and only about 10% (6.8% to 12.2%) are still relieved at 1 year. The only recognised risk factor for failure seems to be the duration of pain (more than 1 year). Other risk factors have been described in the literature, but only in one study and not in the others, such as gender (male or female), age (over or under 70), duration of pain (over or under 1 year), and whether the pain is bilateral or not. In our department, patients are currently treated with lidocaine INTP under neurostimulation. Given the poor results in terms of efficacy and the strong psychological component in chronic pain pathologies, the investigators propose in this study to compare our usual treatment with placebo, since no type of infiltration has ever been compared with placebo, although this is a condition where the placebo effect is likely to be large.

Genetic of Intellectual Deficiency and Autism Spectrum Disorders (RaDiCo-GenIDA)

Evaluation of the Effect of Lomitapide Treatment on Major Adverse Cardiovascular Events (MACE) in Patients with Homozygous Familial Hypercholesterolemia

This is a multicenter, international, long-term observational study investigating the real-world impact of lomitapide on Major Adverse Cardiovascular Events (MACE) in patients with Homozygous Familial Hypercholesterolemia (HoFH). Study Design: Observational, open-label, retrospective and prospective study Data will be collected from >26 lipid centers across Europe Patients will serve as their own control, with comparisons between pre-treatment (3 years before lomitapide) and post-treatment (first 3 years of lomitapide therapy) periods Study Population: Approximately 72 adult patients (≥18 years) diagnosed with HoFH Patients must have received lomitapide for at least 12 months Availability of 3 years of pre-treatment clinical records Objectives: Primary Objective: Evaluate the incidence of MACE before and after lomitapide treatment Secondary Objectives: Assess changes in LDL-C, total cholesterol, liver function tests (ALT, AST, GGT), and lipid-lowering therapy usage (e.g., discontinuation of LDL apheresis, addition of PCSK9 inhibitors) Endpoints: Primary Endpoint: Change in MACE incidence over the 3-year treatment period Secondary Endpoints: Changes in lipid levels, liver safety markers, and adherence to treatment protocols Safety Considerations: The study follows real-world clinical practice, with monitoring of adverse events, including liver-related safety concerns associated with lomitapide Data will be collected in an electronic Case Report Form (eCRF) and analyzed following Good Clinical Practice (GCP) guidelines This study aims to generate real-world evidence on the cardiovascular impact of lomitapide in HoFH patients, addressing an unmet clinical need for data on long-term outcomes.

A Phase 2 Study of PTX 100 in Patients With Relapsed/Refractory CTCL

PTX-100 from a Phase I study shown to help some CTCL patients. This Phase II study will be conducted in a larger population size and there will be initially two groups/arms in the first phase called Phase 2a. This phase will randomize and enroll 20 subjects into the 500 mg/m2 and 20 subjects into the 1000 mg/m2 PTX treatment arms. After determining the recommended optimal dose from phase 2a, for Phase 2b, 75 subjects will then be allocated into this single arm part of the study. Once subject has signed the informed consent, subject will undergo a 28 day screening period, where eligibility would be determined. Once subject is eligible, subject will be dosed with IP. Safety bloods will be taken on the first day of every cycle. Pharmacokinetics (PKs) which are blood samples sent to the Sponsors associated laboratory and will be analysed on how PTX-100 interacts biologically. PKs will be taken on Cycle1Day1(C1D1) to C1D5 and C1D8 for the first 4 cycles. Subject will also undergo skin evaluation and safety exams at every Cycle Day 1. Subjects will also complete quality of life questionnaires at every Cycle Day1. Subjects will be on the study for 18months, until disease progression, unacceptable toxicity, participant or Investigator decision, or until study treatment discontinuation criteria are met, whichever occurs first.

Heat Waves, Urban Heat Islands, and Wellbeing and Health: a Mobile Sensing Approach

While the number of heat wave days in France will likely continue to increase over the century, extreme heat is associated with excess mortality and morbidity in urban heat islands. The first objective of H3Sensing is to investigate outdoor environmental, building, dwelling, situational, and behavioral determinants of objectively assessed personal heat stress over daily movements during warm periods. We will explore environmental determinants associated with micro-urban heat islands at an unprecedented level of accuracy; we will assess building and dwelling characteristics associated with in-home heat stress; and we will examine how daily activities (trips, etc.) and practices (how people dress, manage heat at home) contribute to heat stress. The second aim is to investigate how these heat stress determinants and momentary and cumulated heat stress itself are related to physiological indicators of heat stress, sleep, thermal discomfort, and well-being. One hundred eighty (180) participants recruited through internet advertisements will be followed over 4 day periods in March-May and then a second time in June-September 2025. Research assistants will use a detailed assessment sheet (defined from the a priori visit to 10 dwellings) to collect information on building and dwelling characteristics. Participants will carry a smartphone with a GPS receiver and the Eco Emo tracker application permitting to identify their trips and visited places and to collect additional information on these trips (including their access to air conditioned). GPS data will permit to dynamically assess exposures in participants' everyday mobility. To move beyond simplistic assessments of personal heat stress, we will assess it in an ambulatory way considering personal ambient temperature, humidity, wind speed, and radiant temperature combined into the universal thermal climate index. Additionally, a meteorological station will be placed in the bedroom, while sensors measuring solar flux will be installed outdoor on the windows and balcony. Participants will also carry two bracelets for the measurement of physiological parameters (blood pressure, skin temperature, galvanic skin response as a marker of sweating, and heart rate). As part of the VF++ project, core temperature data will be additionally collected in a subsample of participants (e.g., 20 participants). Personal thermal discomfort, well-being, and sleep quality will be self-reported on the smartphone using the Eco Emo tracker application. An a posteriori phone questionnaire will collect detailed information on heat-related practices and health impacts over the observation period. Analyses of short-term effects will use repeated measure models. Investigations of momentary objective heat stress as the outcome will use statistical techniques for complex mixtures to handle the wide set of exposures. Analyses of sleep quality, well-being, and physiological measures as the outcomes will use two complementary designs: fixed-effect analyses of matched observations in the warm and in the cooler periods for the same participants; and participant-level fixed-effect analyses of pooled observations in the warm period. H3Sensing brings together epidemiologists, urbanists, and climate scientists. As research-to-policy translation, experts in urbanism involved in the project will formulate concrete technical recommendations and will identify practical solutions (in a pedagogical document of synthesis) to help urban actors willing to integrate considerations related to urban heat islands in their urbanistic regulations, public policies, and urban planning projects.

Validation of the Short Form of the "Lower Urinary Tract Symptoms Treatment Constraints Assessment" Questionnaire

For many years, the evaluation of treatments has been a central issue in patient care. The various domains assessed have gradually evolved over time, ranging from satisfaction, improvement and quality of life, to the m ore recent introduction of the Patient Reported Outcome Measure (PROM). These questionnaires or measurement scales (PROMs) focus assessment on the patient and his or her direct experience. Statistical validation of numerous assessment tools has made it possible to quantify objectively many areas of assessment that were initially linked to the patient's feelings, and therefore to their subjectivity. Thus, improvement, quality of life, patient expectations and goal attainment have been the preferred areas for the development of these PROMs. However, certain areas have been sidelined in the creation of these tools. For example, the constraint of care or the side-effects or negative effects of treatment have been little studied using specific assessment tools. In the field of neurology or neuro-urology, only a few multidimensional questionnaires take these domains into account. The main one is Qualiveen, which, in addition to quality of life, looks at discomfort, constraint, fear and patient experience. Other questionnaires, less specific in terms of population, enable a multidimensional evaluation of treatments according to 4 domains (efficacy, side effects, ease of use and overall satisfaction) for the Treatment Satisfaction Questionnaire for Medication (TSQM) or 6 domains (side effects, efficacy, practical aspects of drug treatment, effects of drug treatment on daily life, medical follow-up and overall opinion of treatment) for the Treatment Satisfaction with Medicine Questionnaire (SatMed-Q). These 2 multi-dimensional questionnaires do not allow for a targeted assessment of the constraint of care, which represents a much broader domain than the simple side effect or ease of use of a treatment. What's more, a mixed assessment, both positive (improvement, efficacy) and negative (side-effects) on the same questionnaire, may well limit the interpretation of results and patient understanding. In response to this shortcoming, a specific treatment constraint questionnaire has been developed for neuro-urological treatments in a neurological patient population. The LUTS-TCA (Lower Urinary Tract Symptoms Treatment Constraints Assessment) was developed in French and statistically validated in 2019. This 22-item questionnaire provides a general assessment of therapeutic constraint (physical, social, psychological, etc.). The "detailed" study of therapeutic stress is an important part of the overall therapeutic assessment of these neurological patients, as therapeutic management is often multiple and complex in terms of treatments, examinations, follow-up and impact on daily life. The use of specific, validated tools to take account of care constraints is important, and is just as justified as the assessment of satisfaction or therapeutic improvement. The "detailed" study of care constraints is an important part of the overall therapeutic assessment of these neurological patients, as therapeutic management is often multiple and complex in terms of treatments, examinations, follow-up and impact on daily life. The use of specific, validated tools to take account of care constraints is important, and is just as justified as the assessment of satisfaction or therapeutic improvement. One of the most widely used questionnaires for measuring treatment improvement is the Patient Global Impression of Improvment (PGI-I). The PGI-I takes the form of a single question, with a 7-level Likert scale ranging from +3 (much improved) to -3 (not improved at all). These positive and, above all, negative levels can be confused with the care constraint for the negative part of the response mode. To avoid measuring the same thing twice (negative PGI-I and LUTS TCA), it is vital to be able to measure the 2 parameters independently. The aim of the study is to create a short form of the LUTS TCA in French, in a population of neurological patients. This short form, which would be easier to use and interpret, would simplify its use in everyday practice. Indeed, a large majority of neuro-urology patients suffer from neurodegenerative or progressive pathologies, marked by significant and disabling physical and psychological fatigue symptoms. Long-form questionnaires, or the addition of multiple assessment questionnaires during a single visit to the department, make overall assessment more complex. In addition, this short-form questionnaire is presented in a slightly different form to the long-form version, showing several domains of constraint (physical, social, psychological and care system). This classification should simplify the interpretation and understanding of care constraint, by and for patients.

A Global Phase III Study of Rilvegostomig or Pembrolizumab Monotherapy for First-Line Treatment of PD-L1-high Metastatic Non-small Cell Lung Cancer

This is a Phase III, two-arm, randomized, double-blind, global, multicenter study assessing the efficacy and safety of rilvegostomig compared to pembrolizumab as a 1L treatment for patients with mNSCLC whose tumors express PD-L1.

Implications of Myelin in Executive Control in Adolescence and Early Adulthood

Selection visit - Call for participants for pre-selection - Sending of information forms by mail - Making an appointment for the inclusion visit Inclusion visit at GHU Paris. - Information on the modalities, constraints and foreseeable risks of the study - Collection of informed consent - Verification of inclusion/non-inclusion criteria - Clinical examination: o Verification of medical history and drug treatments - Psychiatric pathology in first-degree relatives - Consumption of toxic substances (nicotine, alcohol, cannabis, etc.) - Manual lateralization will be assessed by the score on the Edinburgh questionnaire (Oldfield, 1971) - Blood sample to measure pubertal hormones (testosterone, estradiol and progesterone levels) - Collection of main medical history and concomitant treatments - Explanation of study procedures - MRI examination - Cognitive assessment