Clinical trial NCT06831877: Study on Deep Transcranial Magnetic Stimulation for Enhancing Insight
Official title: Targeted Intervention Study of Deep Transcranial Magnetic Stimulation for Impaired Insight in Patients with High-Risk and First-Episode Psychosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Impaired Insight
Keywords: Insight
Self monitoring
Anterior cingulate cortex
Medial prefrontal cortex
Deep transcranial magnetic stimulation
Lead sponsor: Shanghai Mental Health Center
Sponsor class: OTHER
First posted: 2025-02-18
Enrollment: 138
Sex: ALL
Minimum age (years): 15
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomly assigned to different montage of stimulation, including deep transcranial magnetic stimulation (active-dTMS) and sham stimulation (sham-dTMS).
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: This study will be carried out at a single center, the Shanghai Mental Health Center (SMHC).

1. 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.
2. 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Clinical Insight
timeFrame: Baseline and immediately after the intervention
Secondary outcomes:
measure: Error-related negativity
timeFrame: Baseline and immediately after the intervention
measure: Resting-state functional activity of the anterior cingulate cortex (ACC) and its functional connectivity with the whole brain
timeFrame: Baseline and immediately after the intervention
measure: Psychopathological symptoms
timeFrame: Baseline and immediately after the intervention
measure: Reality monitoring ability
timeFrame: Baseline and immediately after the intervention
measure: Convertion rate of transition into psychosis
timeFrame: 1-2 year
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Mental Health Center
state: Shanghai
Study officials:
affiliation: Shanghai Mental Health Center
name: Jijun Wang
role: STUDY_DIRECTOR
References: