Clinical trials

Chronic kidney disease (CKD) is a major public health issue worldwide. Hypertension is the first risk factor in patients with CKD for mortality, cardiovascular disease and end-stage renal disease. It's now well established that lowering blood pressure (BP) reduces renal and cardiovascular complications in this high-risk population. In the general population, in addition to lifestyle interventions, the strategy to initiate and escalate a BP-lowering drug treatment is well described. The drug therapies recommended to achieve optimal BP control in the general population are the following: blockers of the renin-angiotensin system (angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB)), diuretics (thiazides and thiazide-like diuretics), and calcium channel blockers. For patients with CKD, the guidelines advise to start the BP-lowering agent with ACEi or ARB, but then, there is no strong evidence to support the preferential use of any particular agent in controlling BP and the results of clinical trials are discordant. In the NephroTest cohort, a French cohort of patients with CKD stage 1 to 5, among 2015 patients, 1782 had hypertension, only 54% had a diuretic and 44% had uncontrolled hypertension. In this cohort, extracellular fluid (ECF) overload was an independent determinant of hypertension, uncontrolled hypertension and apparent treatment resistant hypertension. In the same cohort, ECF overload was independently associated with end-stage kidney disease and death. Our hypothesis is that patients with CKD and uncontrolled hypertension are fluid overloaded and that the second line of treatment after an ACEi or an ARB should be a diuretic. We hypothesize that a specific algorithm to lower BP in patients with moderate to severe CKD based on diuretics will be more effective in term of cardiovascular event, mortality and evolution to end-stage kidney disease as compared to standard of care.

Pain is one of the most frequent patient-reported symptoms in emergency departments (EDs). Pain management could be very challenging, notably for patients that must wait in an ED waiting room. In such context, antalgic drugs that could be used are mainly oral medications with the paracetamol (acetaminophen), the non-steroidal anti-inflammatory drugs and the weak and strong opioid drugs as the main available options, depending on the degree of pain. Those commonly used painkillers, with oral administration, need a delay (approximatively 20 to 30 minutes) before the full analgesic effect could be observed. Methoxyflurane is a self-administered inhaled analgesic used for over 40 years in countries such as Australia. Methoxyflurane has a rapid onset of action, is well tolerated and is widely used for moderate to severe traumatic pain, with several trials that have investigated it efficacy in such indication. However, no data are available concerning the management of non-traumatic painful diseases. Thus, the aim of the open-label, multicenter, and two parallel-arms superiority PAIN-THROX randomized controlled trial is to assess how using self-administered inhaled Methoxyflurane could reduce the time to pain relief comparatively with oral analgesic medications for patients seeking in an ED for non-traumatic painful diseases and who could wait in an ED waiting room.

Twenty-two percent of deliveries in France are induced. In cases where labor is induced and cervix is unfavorable, cervical ripening prior oxytocin administration is advised in order to reduce the risk of cesarean delivery. Cervical ripening agents, pharmacological (prostaglandins) or mechanical are administered during 24 hours. After 24 hours, most women will be either delivered or in labor but 25% of women will require further induction of labor. For 16% of women who undergo cervical ripening, whatever the cervical ripening method, the cervix remains unchanged after 24 hours. The management of these women is not consensual and depends on the maternity unit where women are cared for. This study seeks to identify the most appropriate strategy for the management of women with an unfavorable cervix after 24 hours of cervical ripening, a strategy which would be associated with the lowest maternal and perinatal morbidity but also with the best maternal satisfaction. Because both strategies are practiced in France, the trial would compare: induction of labor with oxytocin and repeated cervical ripening. The aim is to show that repeating cervical ripening is an unnecessary procedure. And more specifically that oxytocin administration is not associated with a higher caesarean delivery rate and that it reduces the time to delivery in comparison with cervical ripening with prostaglandins.

Dissociative symptoms and disorders are particularly prevalent in the general population and among people suffering from psychiatric disorders. To date, no treatment has proven effective for this type of problem. Exploratory studies (without control group) have been carried out. Among these studies, dissociation-focused cognitive behavioral therapy (DF-CBT) seems promising. DF-CBT is based on a solid empirical model that has received numerous scientific evidence.

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.