Targeted Intervention Study of Deep Transcranial Magnetic Stimulation for Impaired Insight in Patients with High-Risk and First-Episode Psychosis
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 138
- 试验地点
- 1
- 主要终点
- Clinical Insight
研究概览
简要总结
Impaired insight is a key factor in the conversion of high-risk individuals to schizophrenia, but there is a lack of targeted interventions. We found that an electroencephalogram (EEG) signal, error-related negativity (ERN), was closely related to impaired insight. The more pronounced the ERN attenuation in patients with high-risk and first-episode psychosis, the more severe the impairement of clinical insight. ERN is a negative potential that appears at the frontal and central scalp electrode locations within 100 ms after an erroneous behavioral response, reflecting the activity of the brain's error-monitoring system. Research has shown that the brain region underlying ERN is partly located in the anterior cingulate cortex (ACC). Other research has reported that the activity extending from the ACC to the medial prefrontal cortex (mPFC) is associated with impaired insight in patients with various disorders. Therefore, this project targets mPFC/ACC and uses deep transcranial magnetic stimulation (dTMS) for targeted modulation, with an exploratory observation of changes in patients' insight before and after neurostimulation.
详细描述
This study will be carried out at a single center, the Shanghai Mental Health Center (SMHC).
- Modulating ACC Functional Activity Using dTMS to Observe Changes in Insight Among FES and CHR Before and After Intervention This study will employ a randomized, double-blind, sham-controlled experimental design. dTMS intervention will be administered for 10 consecutive days, with two sessions per day, ensuring at least a 3-hour interval between sessions. A total of 36 FES participants and 68 CHR participants with impaired insight will be recruited. Participants will be randomly assigned to either the active-dTMS group or the sham-dTMS group to compare changes in insight between the two conditions. This study will conduct clinical assessments and laboratory testing before and immediately after the intervention. Additionally, clinical assessments will be performed at one month and three months post-intervention to analyze the sustained effects of dTMS in modulating ACC functional activity to improve insight.
- Follow-Up of CHR Participants to Analyze the Predictive Role of Insight and ACC Functional Activity on CHR Outcomes A prospective cohort design will be used to compare the transition outcomes among three CHR groups: the active-dTMS group, the sham-dTMS group, and an observational control group. The primary focus is to examine the probability of conversion to schizophrenia at a one-year follow-up and to analyze the extent to which insight and ACC functional activity predict CHR outcomes. 34 CHR participants with intact insight (observational control group) will be recruited for baseline assessments and laboratory testing, followed by a one-year follow-up. By comparing baseline assessments, laboratory indicators, and clinical outcomes between the observational control group and the CHR intervention groups (active-dTMS and sham-dTMS), this study aims to determine whether improvement in insight in the active-dTMS group leads to prognostic outcomes comparable to those of the observational control group. Specifically, it will assess whether the risk of conversion to schizophrenia in the active-dTMS group becomes statistically indistinguishable from that of the observational control group.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Participants will remain blinded to the dTMS montage they receive. The research team will include clinical evaluators, laboratory inspectors, dTMS operators, and statistical analysts. Prior to unblinding, each group of researchers will be blinded to the information collected by the other groups. For example, except for the dTMS operators, no one will know which stimulus montage any participant receives.
After the post-intervention assessments, the first stage of unblinding will take place. At this stage, dTMS operators will provide group identifiers (A and B) to the statistical analysts, but without revealing the corresponding stimulation montages. Once the statistical analysis of group differences is completed, a second stage of unblinding will occur, allowing for further analysis of the clinical trial results, with the corresponding stimulation montage revealed for each group.
入排标准
- 年龄范围
- 15 Years 至 35 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Meet the criteria of clinical high risk for psychosis or meet the DSM-V diagnostic criteria for schizophrenia;
- •Meeting the following definition of impaired insight: below a specific threshold in at least one dimension of the Scale to Assess Unawareness of Mental Disorder (SAI). Specifically, a score of less than 2 in the "awareness of the need for treatment" dimension, less than 3 in the "recognition of illness" dimension, or less than 2 in the "attribution of psychotic symptoms" dimension qualifies an individual as having impaired insight;
- •Having completed at least six years of primary education;
- •Being able to give informed consent, oral or written. Patients under 18 years old give oral consent and their next of kin or legal guardians give written consent.
排除标准
- •Participating in any other clinical intervention research;
- •Meeting the diagnostic criteria of psychotic disorders (including affective disorders);
- •Threshold symptoms are induced by other mental disorders or psychoactive substances;
- •Undergoing anti-psychotic medication for more than 2 weeks;
- •Being diagnosed as organic brain diseases, or severe somatic diseases;
- •Had Experienced traumatic brain injury, and got scores of 7;
- •Dementia, or mental retardation (IQ<70);
- •Being a condition of scalp infection;
- •A pacemaker or other metal implants in the body, pregnancy, or claustrophobia.
研究组 & 干预措施
NoI-CHR
For the observation group of CHR, baseline assessments will be conducted, and follow-up outcomes will be observed one year later. Clinical outcomes will be compared with those of the CHR intervention group.
active-CHR
Individuals with clinical high risk for psychosis (CHR) will be intervened with dTMS.
干预措施: active-dTMS (Device)
sham-CHR
Individuals with CHR, as a control group, will receive sham stimulation.
干预措施: sham-dTMS (Device)
active-FEP
Patients with first-episode psychosis (FEP) will be intervened with dTMS.
干预措施: active-dTMS (Device)
sham-FEP
FEP patients , as a control group, will receive sham stimulation.
干预措施: sham-dTMS (Device)
结局指标
主要结局
Clinical Insight
时间窗: Baseline and immediately after the intervention
Clinical insight will be assessed using the SAI (Schedule for Assessment of Insight). The SAI is a semi-structured interview tool consisting of seven items, with a total score of 14. It evaluates three areas: illness recognition (scoring 0-6), relabeling of symptoms (scoring 0-4), and treatment compliance (scoring 0-4). Patients are considered to have impaired insight if they score less than 3 on illness recognition, less than 2 on relabeling of symptoms, and less than 2 on treatment compliance.
次要结局
- Error-related negativity(Baseline and immediately after the intervention)
- Resting-state functional activity of the anterior cingulate cortex (ACC) and its functional connectivity with the whole brain(Baseline and immediately after the intervention)
- Psychopathological symptoms(Baseline and immediately after the intervention)
- Reality monitoring ability(Baseline and immediately after the intervention)
- Convertion rate of transition into psychosis(1-2 year)