Deep Brain Stimulation of the Ventral Hippocampus in Treatment-resistant Schizophrenia: Exploring the Glutamatergic/GABAergic Mechanisms
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Positive and Negative Syndrome Scale for Schizophrenia (PANSS)
研究概览
简要总结
The goal of this clinical trial is to assess the efficacy and safety of hippocampus-targeted deep brain stimulation (DBS) in treatment-resistant schizophrenia. The main question it aims to answer are:
- whether patients with treatment-resistant schizophrenia can benefit from hippocampus-targeted DBS;
- what is the neural and electrophysiological mechanism underlying the treatment effect of hippocampus-targeted DBS.
详细描述
The first phase of the study will consist of DBS surgery. Participants will receive electrodes implantation in bilateral ventral hippocampus. Continuous stimulation will be applied to optimize and individualize the stimulus parameters. This period is anticipated between 3 and 6 months.
The next phase will consist of the crossover study. Patients who respond to DBS will be randomly assigned to two groups, for a period of 3 months: on stimulation group and off stimulation group. Patients will then be crossed over to the other group for a further 3 months.
Participants will receive PET-CT, clinical assessment and cognitive tests at the main study points to evaluate treatment efficacy and patient tolerance, and to reveal the underlying mechanism of the treatment effect of DBS.
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)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female aged between 18 and 55 years.
- •Having a diagnosis of schizophrenia according to DSM-IV criteria
- •Having a chronic, recurrent course of disease with a five-year minimum duration
- •Determined to be treatment-resistant as demonstrated by:
- •Persistence of positive symptoms which have not responded to appropriate treatments for at least 2 years.
- •Inadequate response from adequate trials of two different classes of antipsychotic drugs (not including clozapine), at least 8 weeks.
- •Inadequate response from adequate trial of clozapine, at least 3 months, or unable to tolerate clozapine because of intolerable side effects.
- •Presence of persistent positive symptom defined as i) requiring a score of 4 (moderate) or more on at least 2 of the next PANSS items: delusions, conceptual disorganization, hallucinatory behavior, suspiciousness and unusual thought content; or as ii) requiring a score of 6 (severe) or more on at least 1 of the above PANSS items.
- •Maintaining stable pharmacological treatment for two months preceding screening visit.
- •Informed consent
排除标准
- •Neurological disease
- •Severe physical illness
- •Contraindications to neurosurgery, MRI or PET-CT;
- •Substance abuse or dependence
- •Mental retardation
- •Female patients who are pregnant or breastfeeding
- •Severe suicide risk and tendencies
结局指标
主要结局
Positive and Negative Syndrome Scale for Schizophrenia (PANSS)
时间窗: Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks
Scale to assess changes in clinical symptoms; response to DBS is defined as a 20% reduction from baseline in PANSS score
次要结局
- Clinical Global Impression-Schizophrenia (CGI-SCH) Scale(Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks)
- The Chinese version of Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery(Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks)
- Clinician-Rated Dimensions of Psychosis Symptom severity (CRDPS) Scale(Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks)
- Cerebral metabolism(PET-CT scans)(Baseline, 24 weeks, 48 weeks)
研究者
Dengtang LIU
Chief Psychiatrist and Professor
Shanghai Mental Health Center