Reduction of Auditory-Verbal Hallucinations in Schizophrenia Through Cortical Neuromodulation: Towards a Closed-loop System
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Duration of auditory-verbal hallucinations
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
盲法说明
Only the person conducting the experiment will know which condition each patient is in.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age > 18 years old
- •Schizophrenic Disorder (Diagnostic and statistical manual of mental disorders, DSM-5-TR, American Psychiatric Association, 2013)
- •AVHs that have resisted to at least two properly conducted antipsychotic therapies at an effective dose for at least 8 weeks (criteria of Kinon et al., 1993)
- •Frequent AVHs (at least 10 times per hour) (Fovet et al., 2022)
- •Unmodified antipsychotic dosage for 30 days prior to inclusion in the protocol
- •AVH are the main residual symptom of schizophrenia.
- •Consent to participate in the study
排除标准
- •Pregnancy (based on date of last menstrual period with possibility of urine test if in doubt)
- •Anticonvulsant therapy
- •Neurological disorder (e.g., multiple sclerosis, epilepsy)
- •Current addictive behavior (except tobacco and cannabis, widely used in this clinical population; Fovet et al., 2022)
- •Contraindication to MRI (i.e., presence of ferromagnetic material or implanted neurostimulation devices due to the risk of displacement or dysfunction such as cochlear implants, cardiac pacemakers, metal splinters in the body following an accident, permanent makeup applied less than 6 months ago, neurosurgical clips, deep brain or vagus nerve stimulation devices, baclofen pumps) (Lefaucheur et al., 2011)
- •Morphological criteria: weight > 130 Kg, abdominal circumference conditioned by the opening of the magnet, shoulder width
- •Lack of coverage by the social security system
- •Current participation in another interventional research protocol or being in the exclusion period of a previous research protocol
- •Refusal to be informed of an brain anomaly detected in the MRI
- •Person under guardianship or curatorship
- •Behavioral disorders or delusions likely to prevent the MRI or rTMS from being performed under good conditions (left to the discretion of the investigator at baseline).
结局指标
主要结局
Duration of auditory-verbal hallucinations
时间窗: During the intervention of Phase 1 (for each active or sham TMS session)
The primary endpoint is the reduction in the duration of AVH (in seconds) during active phasic stimulation sessions compared to sham sessions. Participants will press a button when an AVH occurs (starting the intervention) and press another when the AVH disappears. This allows for the recording of the duration of the AVHs.
次要结局
- 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(Through study completion, an average of 2 years)
- Clinical scales scores(At baseline (before Phase 1), before the intervention of Phase 2 (Day 0, two weeks after the end of Phase 1), after the intervention of Phase 2 (Day 15, Month 1, Month 3, Month 6, Month 12))
- Intensity of auditory-verbal hallucinations(During the intervention of Phase 1 (for each active or sham TMS session))