Clinical trials

A significant proportion of patients remain resistant to antidepressant therapies, even when treatment is well managed. Electroconvulsive therapy (ECT) is a well-established method for treating certain severe and resistant psychiatric pathologies. ECT is also the gold standard for treating mood disorders. Although effective, it is associated with cognitive side effects (memory impairment, post-ECT confusion, longer reorientation time), particularly with bitemporal (BT) montage and brief pulse stimulation. These effects may contribute to patient reluctance and limit adherence to this therapy. From a mechanistic point of view, ECT causes changes in cerebral blood flow (rCBF) and brain electrical activity, particularly in the prefrontal cortex, where the induction of "pseudo-epileptic seizures" appears to be related to therapeutic efficacy, while cognitive side effects appear to be associated with alterations in the temporal areas. The conventional stimulation method results in widespread diffusion of the current due to the properties of the skull, limiting control over the distribution of intracerebral charge densities. In this context, a new approach called "Focal Electrically Administered Seizure Therapy" (FEAST) has been developed to focus the electrical current and limit cognitive side effects. Unlike traditional ECT, FEAST uses unidirectional current and optimized electrode placement, aiming to induce seizures in a more localized manner in the right prefrontal cortex while reducing propagation to temporal regions. The FEAST configuration is based on scientific literature (protocols, parameters, electrode positioning) and not on a "pre configured" mode validated by the medical device manufacturer. Neuroimaging studies suggest that FEAST causes an increase in blood flow in the right prefrontal cortex at the onset of the seizure, followed by a postictal redistribution similar to that observed with ECT, confirming its targeted effect. Open-label clinical trials conducted to date show that FEAST significantly improves depressive symptoms with a more favorable cognitive profile compared to traditional ECT, notably by reducing the impact on autobiographical memory and decreasing the time needed to regain orientation acutely after treatment. Several comparative studies between FEAST and unilateral ultra-brief pulse ECT suggest an advantage in terms of cognitive tolerance, although the differences are not always statistically significant. A multicenter trial also showed comparable effects on reducing suicidal ideation, suggesting that FEAST could be an alternative to traditional ECT. Indeed, preliminary studies indicate that FEAST may offer similar benefits to ECT in terms of reducing depressive symptoms, but with fewer cognitive side effects, which could lead to a better quality of life. Although these studies are promising, they remain few in number and have methodological limitations (open-label clinical trials, feasibility studies, lack of randomization with a comparator arm, small sample size, or assignment to the study arm based on patient preference). There are currently no other randomized clinical trials on FEAST underway or in preparation worldwide. Well-designed, multicenter clinical trials with sufficient patient numbers to achieve satisfactory statistical power are therefore needed to address the limitations of previous studies and explore the clinical benefits of FEAST. The present study is therefore a randomized, multicenter, double-blind clinical trial designed to evaluate the superiority of FEAST in terms of safety and efficacy compared to traditional ECT modalities.

8 participants including 2 pilots. The 2 pilot participants will each execute an MRI acquisition session in order to adjust the experimental paradigm

The disruption of immune system is a key candidate in the pathogenesis of psychiatric disorders, especially those resistant to traditional treatments. Involving complex processes within the brain and peripheral immune system, inflammation may lead to imbalance of neurotransmitter systems and synaptic plasticity and directly contribute to the psychiatric symptoms observed in conditions such as depression, bipolar disorder (BD) and schizophrenia (SCZ). Studies show that treatment-resistant depression (TRD) is associated with elevated levels of inflammatory markers in the blood, which are linked to a lower response to conventional antidepressants. Interventions that modulate this inflammatory response, such as immunomodulatory treatments or therapies targeting pro-inflammatory cytokines, have demonstrated beneficial effects by reducing symptoms and improving patients' quality of life. A thorough understanding of the links between inflammation and treatment resistance therefore paves the way for innovative therapeutic strategies. These approaches could transform current practices by offering more personalized and effective solutions for patients suffering from chronic and resistant psychiatric disorders.

Psilocybin, a serotonin receptor agonist in the brain, significantly and quickly improves depressive symptoms while inducing profound acute subjective effects. The benefit-risk ratio of psilocybin in treatment-resistant depression seems favorable, but needs to be confirmed. Moreover, the role of 5-HT2A receptors, involved in the psychedelic experience, on the therapeutic efficacy of psilocybin is still poorly understood. For example, pre-administration of trazodone, a 5-HT2A antagonist antidepressant, could annihilate the acute subjective effects of psilocybin without altering its beneficial effects (Rosenblat et al., 2023). We intend to test this hypothesis by comparing, in a randomized, double-blind, placebo-controlled study, the effect of two possible doses of trazodone (total or partial occupancy of 5-HT2A receptors) on the benefit/risk ratio of psilocybin. We hypothesize that the therapeutic effects of psilocybin are partially independent of 5-HT2A receptor activation and thus persist even after total or partial neutralization of its acute subjective effects.

Depression and bipolar disorder are frequent, debilitating conditions. Both are thought to be primarily caused by an impaired regulation of mood, which is why they are sometimes referred to as "mood disorders". However, the biological basis of mood remains poorly understood, which is a major limitation for the development of new treatments. Recent work that combines neuroscience with mathematical models are promising to better understand mood and to link it to its biological basis, but they don't have any medical application yet. Can these models describe mood in a way that is relevant to mood disorders, and help doctors and psychologists predict subsequent clinical evolution? With the objective of extending this framework to real-life fluctuations and to assess its clinical relevance, this study will combine a neuroimaging session with a smartphone-based, longitudinal follow-up. Three groups of 96 subjects each will be recruited: depressive disorder, bipolar disorder and healthy controls. They will have their mood fluctuations assessed first in the lab (in the neuroimaging experiment), then in their daily lives (by providing a few ratings and choices every day on the smartphone app). This study will allow to better understand the differences in how patients' mood reacts to daily events, as compared to people who don't suffer from depression or bipolar disorder. The combination of the two steps will allow to assess whether a short neuroimaging evaluation can be useful to predict subsequent clinical evolution during the following months. The investigators wanted to add two optional ancillary studies. The first uses a mobile application for implicit, passive, and longitudinal mood assessments through emotion tracking. Indeed, it seems relevant to add this type of evaluation alongside explicit assessments to more accurately detect mood fluctuations. The second study uses a mobile application that allows voice recordings. The analysis of these vocal parameters will help to characterize a specific linguistic and vocal profile within the three groups, as well as to identify specific symptoms of conditions such as depression and bipolar disorder. These ancillary studies will be offered to both patients and the control group.

Deep brain stimulation (DBS) is a therapeutic approach aimed at applying high-frequency, low-intensity electrical stimulation using electrodes implanted in subcortical structures and connected subcutaneously to a stimulator implanted in the abdomen. In recent years, new indications have been studied for severe and drug-resistant forms of several neurological and neuropsychiatric pathologies. Its non-lesional, reversible and customizable nature make it a therapy of choice. However, several factors are currently slowing down the evolution and optimization of SCP. The identification of objective, quantifiable and predictive criteria for the therapeutic effects of stimulation would allow an acceleration of the individualized identification of the therapeutic parameters of SCP. The surgical procedure for implanting the stimulation equipment is carried out in several stages, which offer unique opportunities to acquire individual imaging or electrophysiology data that are potentially predictive of the therapeutic effect of DBS. In order to continue the optimization of DBS procedures, and therefore to maximize its therapeutic effects, it seems crucial to us to take advantage of all the neurophysiological data likely to be collected during this procedure. Furthermore, given the multiplication of indications for SCP, it seems necessary to highlight specific markers. Thus, the use of neurocognitive and/or motor tests specific to each pathology and coupled with electrophysiological recordings and anatomical and functional examinations would make it possible to highlight specific functional biomarkers predictive of therapeutic effects.

Schizophrenia is a serious psychiatric illness affecting approximately 25 million people worldwide. Patients with schizophrenia experience hallucinations, auditory illusions, disordered thinking, movement disorders, cognitive impairment and social isolation. Treatments with antipsychotics have proven effective in improving their living conditions, but poor compliance results in relapses and rehospitalizations for the majority of patients, which often results in a worsening of residual symptoms. The prevention of these relapses is a major issue in the care of these patients and frequent monitoring is necessary. The use of a simple, rapid and inexpensive tool to monitor symptoms and treatment effect in schizophrenia could improve the effectiveness of the treatment of these patients and prevent relapses. Speech is a good candidate as a biomarker in the monitoring of patients with schizophrenia. Schizophrenia is accompanied by speech disorders including poor speech, variations in tone or intensity or even difficulties in organizing speech.

Approximately 1% of the general population will be affected by schizophrenia over the course of their lives, with life expectancy being reduced by 20 years on average and quality of life being severely diminished in affected individuals. One third of patients suffering from schizophrenia will evolve towards a resistant form of the disease, amongst which many will suffer from auditory-verbal hallucinations (AVH) that current therapeutic approaches struggle to alleviate. Previous work from our team has demonstrated the possibility of robustly inferring the periods of occurrence of AVH from fMRI data, paving the way for the development of a closed-loop neuromodulation system comprised of an electrode array positioned in Broca's area, which would detect AVH in real time, and effector electrodes which would stimulate the temporo-parietal cortex to interrupt them. The aim of this project is to assess the feasibility of this system. To do so, we will first test the ability of transcranial magnetic stimulation of the "continuous theta burst" (cTBS) type, applied at the time of AVH onset, to reduce their duration and intensity, and assess whether this is associated with therapeutic response to the current gold standard rTMS protocol for AVH reduction through neuroplasticity induction. Demonstrating the feasibility of acute suppression of AVH by cortical neurostimulation is an essential element in the feasibility of a closed-loop reactive neuromodulation system. The research project comprises two phases: -Phase 1: randomized controlled clinical trial (1 weekly session per patient over 12 weeks: 6 active stimulation sessions and 6 sham sessions) evaluating the phasic effects of rTMS on AVHs as they appear during the sessions. Phase 2: open-label study offering patients a routine rTMS protocol which has demonstrated its effects on AVH (10 TMS sessions over one workweek - twice daily with 1-hour intervals, MULTIMODHAL study, NCT01373866).

Language is central to children's cognitive, emotional, and social development, and language difficulties are a frequent reason for consultation in child psychiatry, often co-occurring with psychiatric disorders. Yet, systematic language assessment is rarely possible due to the limited availability of speech-language therapists in these services. The TICOALA tool (Interactive Test of Language Comprehension and Learning on tablet) offers a quick and engaging way to evaluate lexical and syntactic comprehension and word learning. This study aims to assess its acceptability among children aged 3-7 attending a child psychiatry service in Paris, as well as among clinicians and parents. Secondary goals include testing the feasibility of a larger study, describing children's language skills, and examining how these relate to clinical and background variables.

The primary objective of this study is to optimize the protocol for the TUS administration in patients with TRD while gaining an initial impression of treatment efficacy.

Efficacy of Transcranial Direct Current Stimulation (tDCS) in the Treatment of Adult Attention-Deficit/Hyperactivity Disorder (ADHD): A Randomized Double-Blind Controlled Trial

An observational behavioural and neurophysiological study of the effects of controlled sensory stimulation (such as music, for example) on brain function

Chronic psychosis, including schizophrenia is now viewed as a progressive disorder where cognitive deficits predate the clinical onset. Early intervention programs improve the general outcome with staged care strategies, supporting the view that the period before and around the first episode of psychosis is a window of opportunity for improving its functional recovery. Pioneering epigenetic analyses indicate that psychosis onset involves oxidative stress and inflammation suggesting that neuroprotective strategies could limit or even prevent the onset of or the transition into a chronic disorder. Several biological factors associated with the emergence of psychosis can all be rectified by using safe and easily accepted supplements including alterations folate deficiency/hyperhomocysteinemia; redox imbalance and deficit in polyunsaturated fatty acids (PUFA). The prevalence of these anomalies (20-30%) justifies a systematic detection and could guide personalised add-on strategy. Cognitive remediation improves quality of life (QoL) and functional outcome in patients with chronic psychosis. It would even be more efficacious in the early phase of psychosis by tackling the negative impact of psychosis on education achievement and employment. However, cognitive dysfunctions are often overlooked in patients at ultra-high risk (UHR) for psychosis and patient with a first episode of psychosis (FEP) and cognitive remediation is not always accessible. New technologies can provide us with youth-friendly, non-stigmatising tools, such as applications with cognitive strategies, motivational tools and functioning guidance personalised according to the need of each individual. Patients can have access to it, wherever they live. Early psychosis can be associated with inflammation, metabolic deficiency, as well as early structural brain anomalies that reflect brain plasticity abilities and could influence the prognosis and response to cognitive training. The study hypothesis is that promoting neuroplasticity by cognitive training and personalised virtual psychoeducation guidance could attenuate or reverse early cognitive deficits and improve the overall functional outcome in young patients UHR or FEP and that this effect is modulated by individual brain plasticity abilities. The overall objective of PsyCARE\_trial is to improve early intervention in psychosis by providing a composite personalised care (CPC) that will enable personalised cognitive training and psychoeducation guidance, adapted to individuals' needs, cognitive abilities and biological background.

Eating disorders (EDs) are complex psychiatric conditions-such as anorexia nervosa and bulimia nervosa-often emerging in young adulthood and associated with high morbidity and mortality. Despite their severity, access to specialized care remains difficult, delayed by shame, stigma, and a lack of insight among patients, as well as long waiting times and limited specialized resources. The AGIS-TCA pilot study aims to evaluate the effectiveness of a systematic minimal early intervention designed to reduce the number of patients lost to follow-up between their request for specialized care and the actual start of treatment. This monocentric, low-risk interventional study will be conducted at the Clinique des Maladies Mentales et de l'Encéphale (CMME), GHU Paris Psychiatrie \& Neurosciences. The intervention includes three early, structured telephone calls and five online support group sessions offered during the waiting period for care. The main objective is to determine whether this proactive approach decreases attrition rates ("lost to follow-up") compared with a historical cohort. Secondary objectives include assessing the acceptability of early phone contact, adherence to support groups, and describing the clinical and sociodemographic profiles of patients requesting care or lost to follow-up. The expected benefit is to facilitate timely access to care for vulnerable patients, prevent symptom worsening, and strengthen engagement in treatment pathways. Risks and constraints are minimal, as participation involves only remote interactions without any invasive procedures.

This project aims to evaluate the impact of relaxation sessions conducted using a virtual reality device on the sleep quality of night-shift healthcare workers. The intervention specifically targets the immediate post-night-shift period, a critical time for recovery, by offering immersive guided relaxation experiences designed to reduce anxiety and promote both mental and physiological relaxation.

This non-interventional study aims to validate the French version of a meningioma-specific quality-of-life questionnaire (MQOL-FR) and to describe health-related quality of life in adults diagnosed with an intracranial meningioma. Participants will be invited to complete online questionnaires through a secure REDCap link. After reading the study information and recording their non-opposition, participants will complete: (1) MQOL-FR (meningioma-specific), (2) EQ-5D-5L (generic health-related quality of life), and (3) FACT-Br (brain tumor-specific quality of life). The questionnaire session takes approximately 30-45 minutes and can be completed in more than one sitting using a REDCap access code. There is no additional visit and no change in usual care. The study will recruit adults (≥18 years) with a meningioma diagnosis based on imaging and/or confirmed by surgery, through the GHU Paris-Sainte-Anne neurosurgery clinic and through patient/community networks. The goal is to obtain 100 fully completed MQOL-FR questionnaires suitable for psychometric analyses.

In the proposed research, we will assess motor and sensory functions of the hand using clinical tests and a tool designed to measure manual dexterity combined with vibrotactile stimulation. We will also evaluate the integrity of brain structure and function using MRI.

Bipolar disorder (BD) is a chronic, cyclical mental illness affecting over 1% of the global population. It is characterized by alternating episodes of elevated mood and energy (mania or hypomania) and episodes of decreased mood and energy (depression). Manic episodes involve hyperactivity, decreased need for sleep, grandiosity, accelerated speech, and sometimes psychotic symptoms such as hallucinations or delusions. Depressive episodes, in contrast, are characterized by sadness, low energy, social withdrawal, sleep and appetite disturbances, and low self-esteem. Bipolar patients are at very high risk of suicide, with rates up to 20 times higher than in the general population; nearly half will attempt suicide during their lifetime, and 15-20% of these attempts are fatal. BD is associated with a substantial decrease in quality of life, often greater than that seen in other mood or anxiety disorders. This reduction is primarily driven by depressive symptoms, including residual ones that may persist during remission periods. The frequent comorbidity with anxiety disorders further exacerbates the burden of the illness. Recently, research has turned toward the concept of the digital phenotype to identify early markers of relapse using passive and continuous monitoring. Among potential digital biomarkers, voice has shown particular promise. Automated speech analysis, combined with machine learning algorithms, has demonstrated effectiveness in detecting psychiatric symptoms and differentiating mood states. In BD, vocal and linguistic patterns vary with mood fluctuations, suggesting that voice could serve as a sensitive indicator of relapse risk. The main hypothesis of the present study is that automated analysis of speech and lifestyle data can help develop a predictive model capable of identifying early signs of relapse, whether manic, depressive, or mixed, or transitions to high-risk states in individuals with bipolar disorder.

Neuropsychiatric disorders are extremely common, severe, and disabling conditions. In the field of psychiatry, they notably include schizophrenia, mood disorders (depressive and bipolar disorders), autism spectrum or neurodevelopmental disorders, obsessive-compulsive disorder, eating disorders, and personality disorders. In the field of neurology, one can cite neurodegenerative diseases (such as Alzheimer's disease, but also frontotemporal dementia or Parkinson's disease, which often represent frequent and challenging differential diagnoses of psychiatric disorders), focal neurological lesions (notably strokes and tumors), or epilepsy. Cognitive impairments are present in nearly all neuropsychiatric disorders and contribute significantly to disability. While impairments in working memory and attention, executive functions, and social cognition have been relatively well studied, other cognitive domains remain largely unexplored in these populations. This is particularly the case for various aspects of motivation, metacognition, conscious access, or causal (Bayesian) inference. Although these domains likely play an important role in prognosis, no consensus currently exists regarding the methods for evaluating these functions. The main objective of this study is to define a multidimensional, transdiagnostic atlas of high-level cognitive impairments-both specific and shared-across severe psychiatric disorders (notably schizophrenia, depressive disorder, bipolar disorder, autism spectrum or neurodevelopmental disorders, and obsessive-compulsive disorder) and neurological disorders (notably neurodegenerative diseases, focal neurological lesions, and epilepsy), by comparing them to healthy volunteers. The investigators also aim to investigate the progression of cognitive impairments over time, across different phases of illness (symptom stabilization or exacerbation) or therapeutic intervention, through longitudinal follow-up of patients being monitored within the recruiting center. Finally, in a more exploratory manner, the investigators aim to investigate the neural correlates of the identified cognitive impairments.

Administration of low-dose selective noradrenaline reuptake inhibitor (sNRI) (e.g. atomoxetine) to healthy subjects is a validated model of increasing cortical noradrenaline levels which, combined with computational modelling of behaviour, allows fine-grained analysis of the impact on learning processes of noradrenaline's fluctuations in the human cortex. The study goal is to characterize the modifications of certain cognitive processes and associated brain circuits under low-dose sNRI using validated computational learning models. The study will be interested in how subjects will modify their learning under the effect of the drug across two separate investigations; one utilizing in a stable evidence accumulation task and one utilising a changing evidence accumulation task. This approach will help to better understand the link between noradrenaline and accumulation of evidence in healthy subjects, and indirectly in some neuropsychiatric pathologies. The study is a single centre, double-blinded, randomized, placebo-controlled, cross-over study involving evaluable healthy adults separated in 2 cohorts: A for participants having the stable task and B for those having the changing one. Participants will then be randomized in a 1:1 ratio to one of the following treatment sequences: * Atomoxetine 40 mg - Placebo (Subgroups A1 or B1); * Placebo - Atomoxetine 40 mg (Subgroups A2 or B2).

During a cessation therapy for tobacco or cannabis, sleep disorders are one of the main risk factors of relapse, and a symptom of substance withdrawing. In this study, we make the hypothesis that identifying and managing potential sleep disorders during cessation treatment may contribute to maintain tobacco / cannabis abstinence on the long-term. To evaluate the impact of such intervention, we will conduct a randomised pilot study among patients consulting at two addiction prevention and care centres, for smoking or cannabis use cessation treatment. Control group will benefit of usual care (a multidisciplinary care with individual and group therapies); intervention group will benefit in addition of a systematic screening of sleep disorders, and in case of a diagnosed alteration, they will be addressed to the Chronos centre, for specific care to help them manage and reduce the consequences of their sleep disorders. Participants will be followed over a 6-month period, with visits at 1 and 3 months, to monitor smoking or cannabis cessation, and other criteria associated with their substance use or sleep.

The goal of this clinical trial is to assess the feasibility of conducting a clinical trial of the use of blue-blocking glasses among patients with a type1 bipolar disorder, experiencing a manic episode. The feasibility criteria include: recruitment rates, participation rates, adherence to the research protocol, the material feasibility of the study. Feasibility criteria will be assessed at the end of the study period. The investigators also want to assess patients' acceptability regarding the use of blue-blocking glasses during a manic episode, using self-reported satisfaction criteria. Those criteria will be monitored at the end of participation period for each patient (7 days after inclusion). In addition, the study will evaluate the impact of the use of blue-blocking glasses on the severity of manic symptoms, sleeping pattern (quality of sleep, sleep latency, night wake, etc.), global functioning, and on suicidal ideations. Those indicators will be assessed at day 0 (inclusion), day 3 and day 7, using validated questionnaires and actimetry data. The study is presented to all patients over 18 years old, with type 1 bipolar disorder, presenting a manic episode, hospitalised in an adult psychiatric ward of Bichat Hospital (GHU Paris). Patients' participation duration is of 7 days after inclusion.

DREPA-COG is an observational study evaluating the effect of exchange transfusions on cognitive function in adults with severe sickle cell disease (SS or Sβ0). Information processing speed is assessed at three time points during the transfusion cycle using the Symbol Digit Modalities Test (SDMT) and additional validated neuropsychological measures. This minimal-risk, fully remote study aims to identify processing speed as a reproducible marker for clinical monitoring and future therapeutic trials.

The CASH study is a randomized, double-blind, placebo-controlled trial evaluating whether adding cilostazol to standard nimodipine therapy improves neurological outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). The primary objective is to assess functional outcome at 6 months using the modified Rankin Scale. A total of 630 patients will be enrolled within 96 hours of aSAH onset and treated for 14 days. The study is conducted across 9 centers in France, funded by a PHRC, and overseen by an independent monitoring board.

The Myelex study is a fundamental research study that aims to better understand how the brain functions and develops. The objective of this study is to better understand the role of myelin, a sheath that surrounds nerve fibers and determines the speed of information propagation in the brain, in cognitive functioning during development in adolescents and young adults. investigator use Magnetic Resonance Imaging (MRI) because this method allows us to study the anatomy and functioning of the brain in a non-invasive (no injection) and painless manner. investigator focus on cognitive control, a set of cognitive functions in the prefrontal cortex, at the front of the brain, that enable the use of the best strategies on a case-by-case basis to solve problems effectively. These functions are closely associated with academic and professional success and develop late, continuing until early adulthood. The goal of this project is simple: to measure the myelin of nerve fibers using MRI and to evaluate the link with the development of cognitive control. Each participant will undergo an MRI examination and cognitive assessments. The study takes place at the Clinical Research Center of GHU Paris and lasts a total of 3.5 hours, including reception, setup, MRI recording, and the completion of a series of cognitive tasks.