Targeted Intervention Study of DTMS on Impaired Insight in Early Psychosis

December 19, 2024 updated by: Shanghai Mental Health Center

A Study on Targeted Intervention for Insight in Patients with First Episode and Clinical High Risk of Schizophrenia Based on Theta Oscillation in Anterior Cingulate Cortex

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 reflecting the function of self monitoring was a potential objective marker of impaired insight. And further functional magnetic resonance imaging (fMRI) analysis showed that the functional connectivity between anterior cingulate gyrus (ACC) and medial temporal gyrus (MTG) was related to insight. Studies have shown that ACC theta oscillation is the key to self monitoring, and theta-alpha phase synchronization between frontotemporal is closely related to cognition. Therefore, this project hypothesized that targeted regulation of ACC theta oscillations could promote theta-alpha phase synchronization and functional connectivity between ACC and MTG, thereby improving patients' insight. The first-episode and high-risk subjects were recruited to detect the theta oscillation of ACC, theta-Alpha phase synchronization and functional connectivity between ACC and MTG using EEG-fMRI. Deep transcranial magnetic stimulation was introduced to regulate ACC theta oscillations. The high-risk subjects were followed up for two years. It was estimated that the theta-alpha phase synchronization of ACC-MTG and insight in the active-dTMS group were significantly improved. And the outcome of the high-risk subjects is better. The project develops neuroregulatory techniques for impaired insight of schizophrenia and is expected to provide a solution for this clinical pain point.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The study will conduct randomized and controlled experimental design, including deep transcranial magnetic stimulation (dTMS) and sham stimulation (SH-dTMS). Each included participant will be given informed consent and then randomly assigned to different montage of stimulation. Participants are blind to the dTMS montage. Researchers in this study will include clinical evaluators, laboratory inspectors, dTMS operators, and statistical analysts. Before unblinding, each group of researchers will have no access to the information collected by the other groups. For example, except the dTMS operators, no one knows which stimulus montage any of the participants receive. The sessions of dTMS will be conducted twice daily for 5 consecutive days, and twice sessions of a day will be separated by 3 hours at least. Clinical assessments and laboratory tests will be administered at baseline and at the end of the last session. After the post-intervention tests, first stage unblinding will be conducted. At this moment, dTMS operators will provide the groups of A and B, but no corresponding montage, to the statistical analysts. After analyzing the differences between the two groups, second stage unblinding will be performed and the results of the clinical trial will be further analyzed by revealing the corresponding stimulus montage of each group. This study will be implemented at a single center, the Shanghai Mental Health Center (SMHC).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200030
        • Shanghai Mental Health Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 35 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 14~35 years old;
  • 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;
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: active-CHR
Participants will be intervened with deep transcranial magnetic stimulation (dTMS).
Device: active-dTMS
The dTMS using H-coil with 5Hz stimulate ACC. The sessions of dTMS will be conducted twice daily for 5 consecutive days, and twice sessions of a day will be separated by 3 hours at least.
Sham Comparator: sham-CHR
Participants, as a control group, will receive sham stimulation.
Device: sham-dTMS
The sham-dTMS has the same appearance with the real stimulation coil, which can not generate magnetic field. A sound generator is built in the coil beat to simulate the sound of the real stimulation.
Active Comparator: active-FES
Patients with first-episode schizophrenia will be intervened with deep transcranial magnetic stimulation (dTMS).
Device: active-dTMS
The dTMS using H-coil with 5Hz stimulate ACC. The sessions of dTMS will be conducted twice daily for 5 consecutive days, and twice sessions of a day will be separated by 3 hours at least.
Sham Comparator: sham-FES
Patients with first-episode schizophrenia, as a control group, will receive sham stimulation.
Device: sham-dTMS
The sham-dTMS has the same appearance with the real stimulation coil, which can not generate magnetic field. A sound generator is built in the coil beat to simulate the sound of the real stimulation.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in clinical insight
Time Frame: Baseline and immediately after the intervention
Clinical insight will be assessed using SAI. SAI is a semi-structured interview tools including seven items, with a total score of 14, 0-6 for recognition of illness, 0-4 for relabeling of psychotic phenomena, and 0-4 for treatment compliance. Patients, with less than 3 scores on recognition of illness, 2 on relabeling of psychotic phenomena, and 2 on treatment compliance, are considered to be improved on insight.
Baseline and immediately after the intervention
Change in error-related negativity
Time Frame: Baseline and immediately after the intervention
The error-related negativity (ERN) is observed over frontocentral sites within 100 ms following an error response in behavioral tasks, reflecting error-detecting activity, and a reduced ERN indicates reduced error monitoring. EEG epochs were marked with artifacts and excluded from the following ERN analysis if on any electrode, (i) the maximal peak-to-peak amplitude exceeded 100 μV within any moving window (width: 200 ms; step: 50 ms) or (ii) the absolute amplitude exceeded 100 μV at any time point. The calculation for the ERN was based on no fewer than five available epochs with erroneous responses.
Baseline and immediately after the intervention
Change in Resting-state functional brain connectivity between anterior cingulate cortex (ACC) and middle temporal gyrus (MTG)
Time Frame: Baseline and immediately after the intervention
Imaging data will be collected on a 3-T Siemens Magnetom Verio syngo MR B17 scanner and a 32-channel head coil, including structural phase and resting stage detection, which will be used to analyze the functional connection between ACC and MTG.
Baseline and immediately after the intervention

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in psychopathological symptoms
Time Frame: Baseline and immediately after the intervention
This study will also observe the psychopathological symptoms, including positive, negative and general symptoms, using PANSS.The reductive ratio of PANSS points will be calculated after dTMS treatment.
Baseline and immediately after the intervention
Covariant change of clinical insight and psychopathological symptoms
Time Frame: Baseline and immediately after the intervention
Clinical insight will be assessed using SAI, and the psychopathological symptoms will be measured using PANSS. The correlation of psychopathological symptoms with clinical insight will be analyzed, especially possible covariant change after dTMS treatment.
Baseline and immediately after the intervention
Change in reality monitoring ability
Time Frame: Baseline and immediately after the intervention
Reality monitoring ability refers to distinguish internally self-generated information from externally-derived information. The test will be carried out by the experimental paradigm of reality monitoring ability.The stimulus materials are easy to be accepted and understood by patients with mental illness.The material consisted of 48 pairs of familiar pictures and was divided into two tests, each consisting of a learning and a testing phase. In the learning phase, 24 pictures will be presented with different combinations of conditions (four combinations of "perceptive/imaginative × left/right" conditions). In the testing phase, one object will be presented and the participants will be asked to decide whether the other paired object is perceptive or imaginative, or whether the image is positioned on the left or right side of the screen.
Baseline and immediately after the intervention
Change in theta oscillation in ACC and theta-alpha phase synchronization between ACC and MTG
Time Frame: Baseline and immediately after the intervention
Theta oscillation and theta-alpha phase synchronization will be recorded using using a magnetic resonance compatible 64 electrode cap (BrainAMP MR, Brain Products, Munich, Germany) based on the international society for electroencephala 10/20 standard system.
Baseline and immediately after the intervention
Convertion rate of transition into psychosis
Time Frame: 2 year
This study will use SIPS to identify individuals with CHR and assess the participants' clinical outcomes, including transition into psychosis, symptomatic, remission, and other disorders
2 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Shanghai Mental Health Center

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Jijun Wang, Doctoral, Shanghai Mental Health Center
  • Study Director: Tianhong Zhang, Doctoral, Shanghai Mental Health Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 5, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 11, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 14, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 19, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • DTMS2024

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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