Clinical trials

The primary objective of the AMIVAT trial is to assess whether a 5-day course of inhaled amikacin, compared to placebo, reduces the incidence of progression to ventilator-associated pneumonia (VAP) at day 28 in intensive care unit (ICU) patients with ventilator-associated tracheobronchitis (VAT). Transition from VAT to VAP will be defined as the occurrence of a first VAP episode due to the same pathogens than those responsible for VAT.

Superficial venous malformations (SVMs) are rare congenital anomalies that present as bluish masses. These masses may be focal, with limited skin involvement, or segmental, with more extensive involvement. They may be associated with syndromic conditions such as blue rubber nevus syndrome. SVMs are characterised by a progressive worsening course, with repeated episodes of superficial venous thrombosis occurring. These episodes become more frequent over time, causing acute, intense and often highly debilitating pain. To limit progression and in cases of functional impairment, long-term treatments may be offered. These include venous compression, targeted therapies such as mTOR inhibitors, and, where possible, surgical treatment or sclerotherapy. However, the management of intra-SVM superficial venous thrombosis is not currently standardised, especially in the pediatric population. This study aims to evaluate the benefits of Acetylsalicylic acid (ASA) as an add-on treatment to local non-steroidal anti-inflammatory drug for the management of thrombotic episodes in superficial venous malformations in children aged 6 to 17 years.

Depression in neurocognitive disorders (Alzheimers' disease and related disoders) is a highly prevalent condition, especially in nursing homes. While it is associated with significant distress, the current conventional antidepressants have shown only modest efficacy and exposed to potentially severe side effects. Recent evidence suggests that nitrous oxide (N2O) in its most commonly used packaging of EMONO (Equimolar Mixture of Oxygen and Nitrous Oxide) has rapid antidepressant properties and a good safety profile. However, no study has investigating the antidepressant effect of EMONO in a population of depressed older adults with moderate to severe neurocognitive disorders in nursing homes. The principal goal of the PROTO-EHPAD study is to compare the changes in depressive symptoms in such individuals in a randomized controlled trial with a follow up period of 8 weeks, with a dosage escalation procedure.

Atrial fibrillation is the most frequent cardiac rhythm disorder and its prognosis is essentially marked by the risk of embolic events. Its treatment is based on long-term oral anticoagulant therapy according to the risk of embolic events assessed by risk scores such as the CHA2DS2-Vasc score, but this prescription is associated with a risk of hemorrhagic events that must be taken into consideration when deciding on the treatment for a given patient. There are two categories of validated oral anticoagulant treatments for the prevention of embolic events in atrial fibrillation: antivitamin K agents, which have long been the reference treatment but are restrictive and difficult to use because of a narrow therapeutic window, and direct oral anticoagulants, which are now the first-line treatment but have not been evaluated in phase II and III studies in patients with severe renal failure. End-stage renal disease (clearance \<15 mL/min/1.73m2), particularly at the dialysis stage, is a risk factor for cardiovascular disease in its own right, and a significant number of patients develop atrial fibrillation. Given the co-morbidities associated with renal failure, in particular hypertension, patients with renal failure undergoing dialysis and suffering from atrial fibrillation are generally at a higher risk of embolism than patients without renal failure, but also at a higher risk of bleeding. Thus, if the indication for prescribing oral anticoagulant therapy is clear in this population, the associated bleeding complications are also more frequent and more serious in these patients who have regular vascular accesses in the context of hemodialysis. There is thus a real need for reliable therapeutic alternatives with a better benefit/risk ratio than antivitamins K. Translated with www.DeepL.com/Translator (free version)

Induction therapy decreases the rate of acute allograft rejection in kidney transplant recipients (KTRs) and is strongly recommended. Polyclonal lymphocyte-depleting antibodies and interleukin-2 receptor (IL2R) antagonists are therefore widely used around the world, with a leading position for rabbit anti-thymocyte globulin (rATG, Thymoglobulin®) and basiliximab (Simulect®), respectively. The actual immunological risk of the sensitized KTRs without donor specific antibodies (DSAs) is still debated. The benefit-risk equation of lymphocyte depleting antibodies (versus IL2R antagonists) is not known in sensitized KTRs without DSAs. This clinical trial will compare the efficacy and safety of basiliximab and rATG in sensitized KTR without pre-existing DSAs detected by Luminex.

Despite pharmaceutical innovations, chemotherapy induced nausea is frequent and largely participating to alter our patients quality of life. Non invasive vagal stimulation is approved in other health issues, for example in headache or gastroparesis, with a reported benefit on nausea. This study aims to analyse if a non invasive vagal stimulation could better prevent chemotherapy induced nausea, in addition to standard treatment, in breast cancer patients treated with cyclophosphamide and anthracycline.

The goal of this observational study is to evaluate intra-individual neurophysiological variability in children and adults with and without NeuroDevelopmental Disorders (NDD), for several sensory modalities and types of stimulation. The main hypotheses are: * NDD participants and children exhibit higher intra-individual variability than other participants * intra-individual neurophysiological variability is correlated to behavioral, psychological and learning profiles Participants in this study will: * be recorded for EEG and other neurophysiological parameters while exposed to sensory stimulations, to quantify sensory neurophysiological variability * perform behavioral tests and fill out questionnaires, to establish the behavioral and psychological profile * train for perceptual learning, to measure learning abilities These evaluations will be split in 3 visits spread on a maximum of 3 months, and training for learning will be done at home in between 2 visits.

Bevacizumab is a standard drug for metastatic colorectal cancer (mCRC) in combination with cytotoxic chemotherapy. However, inter-individual pharmacokinetic variability was observed for bevacizumab and an exposure-response relationship for efficacy was described for bevacizumab in mCRC patients treated with 1st-line bevacizumab-based chemotherapy.

Treatment and prevention of respiratory infections are of great interest in many medical areas. Create a physical device covered by primary human nasal cells could be very usefull in order to analyse delivery and efficiency of drugs. In this context the aim of this project is to create a collection of primary cells from the human nasal epithelium. This collection will be realised during programmed surgery, thanks to a specific device dedicated to collect nasal cells. Then the cells will be sent to the lab in order to grow at the air-liquid interface, which is an excellent 'ex vivo' model for their study.

Epidemiological studies show that one person in eight suffers from at least one psychiatric disorder. Mental health is therefore a major public health issue, and care for these disorders must continue to be improved. The management of mental disorders has long followed the traditional categorical approach of developing a treatment for a given disorder. However, researchers have recently pointed out the limits of this approach in the field of mental health. They highlight the large number of co-morbidities, the existence of aspecific disorders and the intra-diagnostic heterogeneity of patients. These factors have led them to develop a transdiagnostic approach, which focuses on the mechanisms common to the various disorders in order to treat them at the same time and thus reduce the cost of treatment.

The goal of this clinical trial is to evaluate the efficacy on lung function after 24 weeks of rituximab + MMF combination comparatively to placebo + MMF combination in patients with SSc-ILD severe at the initial assessment or at high risk of progression.

Autism Spectrum Disorder (ASD) is defined as a neurodevelopmental disorder that affects the functioning and development of social communication (DSM5 - 2013). ASD causes particularities in sensory treatments (auditory, visual), qualified as uni-modal. Added to this, there is difficulties to deal with prevailing stimuli of the environment (pluri-modal) ; parents report the discomfort of their child in this situation with "noisy" behavioral manifestations. Therapeutic social skills programs most often address the subject's lack of adjustment to their environment through understanding social rules and codes and cognitive treatment of situations. Thus, in order to relieve the sensory modulation disorders which can be the cause of social adjustment difficulties, it's propose to exercise the sensory habituation of children with ASD thanks to virtual reality scenarios restored in 3D immersion booth (the CAVE). The child will be exposed to multimodal stimulation during immersion sessions reproducing the conditions of an ecological environment. A therapist will accompany the child in the CAVE throughout the session. The investigators hypothesize that regular and repeated exposure to a simulated environment in the CAVE can improve multisensory treatment capacities and have a beneficial effect on the autonomy of children and adolescents with ASD in everyday situations.

The overall objective of the research project presented here is to assess the prevalence of fibromyalgia in patients being treated for ADHD, the prevalence of ADHD in patients being treated for fibromyalgia, and the neurobiological correlates of ADHD-fibromyalgia comorbidity.

The GENOPHEN study aims to explore the links between the genome, metabolomic profile, and clinical phenotype in adults with early-treated PKU.

This study will establish a prospective, multicenter national cohort of patients with spontaneous intracerebral hemorrhage (ICH). A standardized multimodal database integrating clinical, biological, and imaging data will be collected. The study aims to better characterize ICH patient phenotypes, identify diagnostic and prognostic biomarkers, and describe adherence to evidence-based acute management strategies, including the proportion of patients managed according to the care bundle validated in the INTERACT 3 study. The cohort is also intended to provide a structured platform for translational research and the preparation of future stratified interventional clinical trials in spontaneous ICH.

This will be a single-center, prospective, analytical cohort study. All included patients will undergo transcranial ultrasound (TPI) with measurement of cerebral pulsatility parameters prior to subtractive lumbar puncture during hospitalization in the neurosurgery department, followed by a second ultrasound assessment either at one year after surgery for operated patients, or at one year after the initial ultrasound assessment for non-operated patients. This ultrasound evaluation will be integrated into the routine work-up, which is already systematically performed in cases of suspected idiopathic normal pressure hydrocephalus (iNPH). The neurosurgical team's decision to perform cerebrospinal fluid (CSF) shunting will be made blinded to the ultrasound measurements and based solely on the standard clinical protocol. The primary objective of the study is to demonstrate that the mean amplitude of cerebral pulsatility (MeanBTP) prior to subtractive lumbar puncture is significantly higher in patients who show clinical improvement 12 months after CSF shunting compared with those who do not, with a type I error risk (alpha) of 0.05."

Evaluation of the prediction of clinical response to rituximab at a dose of 1000 mg once using a pharmacological model including several pharmacokinetic and pharmacodynamic parameters.

Episodic memory (EM) is a neuropsychological marker of Alzheimer's disease (AD) (Thomas-Anterion, 2006). Current tests for its assessment do not take into account the identity and emotional aspects of memory (Van der Linden et al., 2018). However, there are models that integrate links with identity, self-awareness and experience. Pause et al. (2013) propose criteria to create ecological tools, including consideration of the emotional valence of memories and the spatio-temporal context of acquisition. In line with these criteria, we have developed a new tool: the NEM (New evaluation of Episodic Memory). Preliminary studies show different response profiles on the NEM among patients (Launay et al., 2023). We now want to evaluate the relevance of this tool in the differential diagnosis of AD.

Rheumatoid arthritis is an autoimmune disease that can affect various organs, including the lungs, and lead to rheumatoid arthritis-interstitial lung disease (RA-ILD). RA-ILD is responsible for increased mortality in rheumatoid arthristis (RA) patients. The prevalence of RA-ILD varies according to the screening tool used. The current gold standard is chest CT, but this is an expensive, time-consuming and irradiating examination, and recommendations on when and how often it should be performed are not clearly established. Lung ultrasound (LUS) is an emerging tool for the detection of lung parenchymal damage, particularly in systemic scleroderma and idiopathic pulmonary fibrosis (IPF). LUS is a non-irradiating, non-expensive examination that can be performed rapidly. The aim of our study is to evaluate LUS as a screening tool for RA-ILD, in patients with risk factors for developing RA-ILD.

This study evaluates the variation of expression of the neonatal Fc receptor (FcRn) in Natural Killer T Cells Expressing an Invariant T Receptor (iNKT) and monocytes along with the surface expression of Fc gamma type II receptor (RII) and RIII in active or newly diagnosed lupus patients compared to inactive lupus patients.

Following an initial consultation with a memory, resources and research centre (MRRC) doctor, a day hospital may be prescribed to carry out an assessment of cognitive disorders. Patients are then usually followed up in consultation at least once a year, in the framework of a new day hospital and/or consultations with a MRRC doctor.

The treatment of child's vertebral malformations has evolved a lot including the realization of surgical vertebral resections. The surgical techniques used are multiple, require heavy surgery, one or more approaches and surgical time, transfusions, a neurological risk (up to 20% in some series, risk of non-consolidation, insufficient correction). These surgical techniques deserve an evaluation of the early complications and the skeletal maturity of these children (maintenance of the surgical correction, evolution of the associated curvatures).

Intensive care is a unit that admits ventilated patients. Hospitalization is extremely challenging for these patients. Their vital prognosis is at stake, and they often have difficulty moving due to pain, edema, neuromyopathy, or the presence of monitoring cables. They are also hindered in their communication: they cannot speak because of the presence of the intubation tube between their vocal cords or the tracheostomy cannula with the inflated cuff. Every day, in each intensive care unit, about 50% of ventilated patients are conscious and face communication difficulties. They describe this difficulty as a "nightmare." This leads to challenges in care management and increases the anxiety caused by hospitalization in the intensive care unit. A large proportion of patients will develop post-intensive care syndrome. The tools currently used are not efficient. Moreover, many patients have comprehension difficulties due to the medications administered to them (sedatives) or due to the initial or secondary pathologies related to their hospitalization (confusional syndrome, ICU delirium). Our objective is to implement an adapted and personalized communication tool for ventilated patients in intensive care.

Community acquired pneumonia, in particular when requiring oxygen therapy because of acute hypoxemic respiratory failure and meeting acute respiratory distress syndrome (ARDS) criteria frequently leads to tracheal intubation and poor outcome. Among invasively mechanically ventilated patients with ARDS and presenting a PaO2/FiO2 ratio (arterial partial pressure of oxygen to inspired fraction of oxygen) of less than 150 mmHg, the prone position significantly reduces mortality and represents standard care (Guérin 2013). Among non-intubated COVID-19 patients, a subtype of viral community acquired pneumonia, a recent study showed that awake prone positioning reduces the composite outcome of intubation or death among patients requiring nasal high flow therapy. Furthermore, it favored weaning of nasal high flow therapy. Prone position in patients with non-COVID ARDS treated with high nasal flow was evaluated in 20 patients with predominantly viral pneumonia (Ding 2020) and was associated with improved oxygenation. Coordinating investigator hypothesize that prone positioning of patients suffering non-COVID community acquired pneumonia and undergoing nasal high flow therapy can significantly improve outcome by reducing the need for intubation and associated therapies such as sedation and muscle relaxation.

Erysipelas (superficial cellulitis) is a frequent streptococcal bacterial infection. Each episode of erysipelas may worsen preexisting lymphedema and evolve to life-threatening necrotizing soft-tissue infection. Moreover, each attack of cellulitis may worsen lymphatic damage and therefore favour additional attacks. Recurrence is frequent: 10-30% of cases and even up to 50%. In this context, at least 2 episodes of erysipelas in the same limb during a 1-year period defines recurrent erysipelas requiring prophylaxis. Such prophylaxis is based usually on penicillin therapy. Compression was evaluated only in a monocentric randomized controlled trial, and was never compared to antibioprophylaxis. The investigators hypothesized that compression therapy alone might represent a single intervention for prophylaxis of erysipelas recurrence as efficient as long-term antibiotic prophylaxis with compression therapy combined. This study is a multicenter, parallel groups, assessor-blinded, non-inferiority, randomized clinical trial. Main objective is to evaluate whether supervised compression therapy alone is non-inferior to supervised compression therapy + oral penicillin in controlling relapse of recurrent erysipelas. Secondary objectives are to assess time to first recurrence ; to assess the severity of the recurrence ; to assess the safety of the intervention to assess the quality of life during the prophylaxis phase ; to assess the adherence of patients with the intervention and to assess, in a joint analysis, that supervised compression therapy is both not inferior in terms of QALY and not more expensive at 1 year than supervised compression therapy + antibiotic. The study will included male or female adults who have had at least 2 episodes of recurrent erysipelas at the same leg within the previous 52 weeks, and no more than five episodes of erysipelas in the same areas of the lower limbs during the year before randomization. Experimental group is supervised compression therapy + emollient cream during 12 months and control group is supervised compression therapy + emollient cream + oral penicillin (phénoxyméthylpénicilline) during 12 months Main outcome is the proportion of patients with at least one recurrence of erysipelas during the 1-year prophylaxis phase, performed by an assessor-blinded. Patients will be identified in a hospital setting, or referred by physicians servicing the local region, or by direct advertising through patients' associations. If the patient gives consent to participate, at the end of a inclusion visit (V0), the randomization will be performed via the e-CRF. Prescriptions will then be issued on inclusion. Control group who will start antibiotic treatment at inclusion. A run-in period of 7 ±2 days will be planned between V0 and the beginning of the compression therapy for the both group, in order to get the prescribed elastic stockings, and to train the nurse in charge of the compression supervision. A nurse trained in the study will supervise the first applications of the compression in the patient's home. After inclusion visit (V0), a home visit by the liberal IDE will be planned at M1 for to check daily adherence (use of ATB or/and wearing compression and application of emollients). A patient diary must be completed from inclusion and during the follow-up period. Two telemedicine clinic were scheduled at M3 and M9 and two study visits were scheduled at M6 and M12 with a complete physical examination. All the evaluations will be performed by a blinded evaluator investigator. Supplementary telemedicine clinic(s) in case of potential recurrence of erysipelas will be done by the blinded evaluator in the presence of the nurse who will be at bedside of patient. The organization and design of the study will be realistic, and thus is designed to facilitate its feasibility and generalizability of results. In case of demonstration of non-inferiority of supervised compression therapy, patients with recurrent erysipelas will be spared of antibiotics first-line, and therefore suppress the impact of both long-term antibiotics on gut microbiota individuals and health burden of antibiotics at the population level.