A Study on the Brain Mechanism of cTBS in Improving Medication-resistant Auditory Hallucinations in Schizophrenia

August 20, 2024 updated by: Guo Wenbin, Central South University
This study is dedicated to exploring the brain mechanism of medication-resistant auditory hallucinations and developing effective treatment methods for them by using both cross-sectional and longitudinal designs. The continuous theta burst stimulation(cTBS) treatment mode, with the left cerebellum Crus II as the stimulation target, is applied to treat the schizophrenia patients with the medication-resistant auditory hallucinations. At the same time, the first-episode schizophrenia patients with auditory hallucinations were recruited as a test cohort to examine that brain mechanism of general auditory hallucinations in schizophrenia may be the structural and functional abnormalities in the temporoparietal circuit.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Previous studies have shown that repetitive transcranial magnetic stimulation (rTMS) targeted at the temporal-parietal junction can effectively treat genenal auditory hallucinations in schizophrenia, but it is not the case for medication-resistant auditory hallucinations. Studies suggested that rTMS targeted at the left Crus II might be effective for medication-resistant auditory hallucinations. This study is dedicated to exploring the brain mechanism of medication-resistant auditory hallucinations and developing effective treatment methods for them by using both cross-sectional and longitudinal designs. The continuous theta burst stimulation(cTBS) treatment mode, with the left cerebellum Crus II as the stimulation target, is applied to treat the schizophrenia patients with the medication-resistant auditory hallucinations. Assessment with symptomatology, neuropsychology, neuroimaging, and machine learning methods is utilized to examine the investigators hypothesis that structural and functional abnormalities of the cerebral cortico-cerebellar-thalamic-cortical circuit (CCTCC) may contribute to brain mechanism of medication-resistant auditory hallucinations in schizophrenia. At the same time, the first-episode schizophrenia patients with auditory hallucinations were recruited as a test cohort to examine that brain mechanism of general auditory hallucinations in schizophrenia may be the structural and functional abnormalities in the temporoparietal circuit, whereas structural and functional abnormalities of the CCTCC may contribute to brain mechanism of medication-resistant auditory hallucinations in schizophrenia.

Study Type

Interventional

Enrollment (Actual)

200

Phase

  • 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
      • Changsha, China
        • The Second Xiangya Hospital of Central South University

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

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. Written informed consent
  2. 18-45 years old, right-handed
  3. Meet the diagnostic criteria for schizophrenia according to the Structural Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V)
  4. After a sufficient course of antipsychotic treatment (more than 6 weeks, two or more antipsychotic drugs, at least one of which is the second generation of atypical antipsychotic drugs), auditory hallucinations occurred more than 5 times a day for more than 6 months
  5. Stable antipsychotic medication 4 weeks before and during the treatment (except auditory hallucination symptoms)

Exclusion Criteria:

  1. A history of epilepsy, convulsions, stroke or other serious brain diseases
  2. There are serious infectious diseases, malignant tumors, and severe somatic comorbidity
  3. Mental retardation, personality disorder and so on
  4. Contraindications for magnetic resonance imaging
  5. Diagnose of substance dependence or abuse as primary clinical problem
  6. Pregnancy
  7. Participants had received Modified Electraconvulsive Therapy (MECT) or TMS treatment in recent 6 months

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: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: The schizophrenia patients with medication-resistant auditory hallucinations
Drug + cTBS intervention (the left cerebellum Crus II as the stimulation target)
Drug: Antipsychotic drugs
Stable antipsychotic medication 4 weeks before and during the treatment. Chlorpromazine (CPZ) equivalent dosages were calculated for second- and first-generation antipsychotic drugs
Other Names:
  • MRI scan
Device: cTBS （the left cerebellum Crus II as the stimulation target）
Participants received 3 daily sessions of cTBS treatment. One session of cTBS was 40 seconds in duration and consisted of 3-pulse bursts at 50 Hz repeated every 200 milliseconds (5 Hz) until a total of 600 pulses was reached. To achieve cumulative aftereffects, this protocol was repeated 3 times and (1800 pulses in total) separated by two 15 minute breaks
Other Names:
  • MRI scan
Active Comparator: The schizophrenia patients with general auditory hallucinations
Drug intervention
Drug: Antipsychotic drugs
Stable antipsychotic medication 4 weeks before and during the treatment. Chlorpromazine (CPZ) equivalent dosages were calculated for second- and first-generation antipsychotic drugs
Other Names:
  • MRI scan
No Intervention: The healthy controls
MRI scan at baseline and no drugs treatment
Experimental: Drug + cTBS intervention: the first-episode schizophrenia patients with auditory hallucinations
Drug + cTBS intervention (the left temporoparietal cortex as the stimulation target)
Drug: Antipsychotic drugs
Stable antipsychotic medication 4 weeks before and during the treatment. Chlorpromazine (CPZ) equivalent dosages were calculated for second- and first-generation antipsychotic drugs
Other Names:
  • MRI scan
Device: cTBS（the left temporoparietal cortex as the stimulation target）
Participants received 3 daily sessions of cTBS treatment. One session of cTBS was 40 seconds in duration and consisted of 3-pulse bursts at 50 Hz repeated every 200 milliseconds (5 Hz) until a total of 600 pulses was reached. To achieve cumulative aftereffects, this protocol was repeated 3 times and (1800 pulses in total) separated by two 15 minute breaks
Other Names:
  • MRI scan
Active Comparator: Drug intervention: the first-episode schizophrenia patients with auditory hallucinations
Drug intervention
Drug: Antipsychotic drugs
Stable antipsychotic medication 4 weeks before and during the treatment. Chlorpromazine (CPZ) equivalent dosages were calculated for second- and first-generation antipsychotic drugs
Other Names:
  • MRI scan
Experimental: The schizophrenia patients with medication-resistant auditory hallucinations from the fourth arm
Drug + cTBS intervention (the left cerebellum Crus II as the stimulation target)
Drug: Antipsychotic drugs
Stable antipsychotic medication 4 weeks before and during the treatment. Chlorpromazine (CPZ) equivalent dosages were calculated for second- and first-generation antipsychotic drugs
Other Names:
  • MRI scan
Device: cTBS （the left cerebellum Crus II as the stimulation target）
Participants received 3 daily sessions of cTBS treatment. One session of cTBS was 40 seconds in duration and consisted of 3-pulse bursts at 50 Hz repeated every 200 milliseconds (5 Hz) until a total of 600 pulses was reached. To achieve cumulative aftereffects, this protocol was repeated 3 times and (1800 pulses in total) separated by two 15 minute breaks
Other Names:
  • MRI scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Psychotic Symptom Rating Scales-Auditory Hallucination Subscale (PSYRATS-AH)
Time Frame: From baseline to 10 weeks
The Psychotic Symptom Rating Scales-Auditory Hallucination Subscale (PSYRATS-AH) is an instrument designed to quantify the severity of hallucinations before and after treatment at different follow up point. Raw score range is 0-44. A higher score indicates a worse outcome.
From baseline to 10 weeks
Structural and Function MRI data
Time Frame: From baseline to 10 weeks
A 3.0 T Siemens scanner was used to obtain the fMRI images in the Second Xiangya Hospital of Central South University.The MRI data wii be obtained before and after treatment at different follow up point.
From baseline to 10 weeks
Positive and Negative Syndrome Scale (PANSS)
Time Frame: From baseline to 10 weeks
The PANSS total scores, subscale scores were used to evaluate the severity of psychotic symptoms for schizophrenia before and after treatment at different follow up point.The total score of the PANSS was more than 60.The higher scores mean a worse outcome.
From baseline to 10 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
Time Frame: From baseline to 10 weeks
Pre-post assessment of cognitive function via Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
From baseline to 10 weeks
The Stroop test
Time Frame: From baseline to 10 weeks
Pre-post assessment of cognitive function via the Stroop test
From baseline to 10 weeks
Wisconsin Card Sorting Test (WCST)
Time Frame: From baseline to 10 weeks
Pre-post assessment of cognitive function via Wisconsin Card Sorting Test (WCST)
From baseline to 10 weeks

Collaborators and Investigators

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

Sponsor

Central South University

Investigators

  • Principal Investigator: Wenbin Guo, Central South University

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 (Actual)

September 9, 2021

Primary Completion (Actual)

October 31, 2023

Study Completion (Actual)

November 30, 2023

Study Registration Dates

First Submitted

August 31, 2021

First Submitted That Met QC Criteria

September 2, 2021

First Posted (Actual)

September 9, 2021

Study Record Updates

Last Update Posted (Actual)

August 21, 2024

Last Update Submitted That Met QC Criteria

August 20, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 82171508

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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