protocolSection identificationModule nctId: NCT06361160, orgStudyIdInfo id: D23-P037, briefTitle: Reduction of Auditory-Verbal Hallucinations in Schizophrenia Through Cortical Neuromodulation, acronym: HALLUSTIM, statusModule overallStatus: NOT_YET_RECRUITING, startDateStruct date: 2024-04, primaryCompletionDateStruct date: 2026-04, completionDateStruct date: 2026-04, studyFirstPostDateStruct date: 2024-04-11, lastUpdatePostDateStruct date: 2024-04-11, sponsorCollaboratorsModule leadSponsor name: Centre Hospitalier St Anne, class: OTHER, descriptionModule briefSummary: 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)., conditionsModule conditions: Treatment Resistant Schizophrenia, designModule studyType: INTERVENTIONAL, phases: NA, designInfo allocation: RANDOMIZED, interventionModel: CROSSOVER, interventionModelDescription: Patients (20) suffering from resistant schizophrenia will be enrolled over a 12-month period and will be randomized in a (1:1) ratio to start with either active or sham Transcranial Magnetic Stimulation (TMS) for the first of their 12 sessions, which will then alternate from one condition to the other for each patient., primaryPurpose: TREATMENT, maskingInfo masking: TRIPLE, maskingDescription: Only the person conducting the experiment will know which condition each patient is in., whoMasked: PARTICIPANT, whoMasked: CARE_PROVIDER, whoMasked: OUTCOMES_ASSESSOR, enrollmentInfo count: 20, type: ESTIMATED, armsInterventionsModule interventions name: Active Transcranial Magnetic Stimulation (TMS), interventions name: Sham Transcranial Magnetic Stimulation (TMS), outcomesModule primaryOutcomes measure: Duration of auditory-verbal hallucinations, secondaryOutcomes measure: Clinical scales scores, secondaryOutcomes measure: Measure of the duration and/or intensity of HAV (in seconds) during active phasic stimulation sessions compared to sham sessions (phase 1) among TMS responders and non-responders in phase 2, secondaryOutcomes measure: Intensity of auditory-verbal hallucinations, eligibilityModule sex: ALL, minimumAge: 18 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule, hasResults: False