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

Sponsor
Central South University (Other)
Overall Status
Recruiting
CT.gov ID
NCT05039489
Collaborator
(none)
200
Enrollment
1
Location
6
Arms
26.7
Anticipated Duration (Months)
7.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Antipsychotic drugs
  • Device: cTBS（the left temporoparietal cortex as the stimulation target）
  • Device: cTBS （the left cerebellum Crus II as the stimulation target）
 N/A

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 Design

Study Type:
Interventional
Anticipated Enrollment :
200 participants
Allocation:
Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Study on the Brain Mechanism of cTBS in Improving Medication-resistant Auditory Hallucinations in Schizophrenia
Actual Study Start Date :
Sep 9, 2021
Anticipated Primary Completion Date :
Oct 31, 2023
Anticipated Study Completion Date :
Nov 30, 2023

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Psychotic Symptom Rating Scales-Auditory Hallucination Subscale (PSYRATS-AH) [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.

    2. Structural and Function MRI data [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.

    3. Positive and Negative Syndrome Scale (PANSS) [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.

    Secondary Outcome Measures

    1. Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) [From baseline to 10 weeks]

      Pre-post assessment of cognitive function via Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)

    2. The Stroop test [From baseline to 10 weeks]

      Pre-post assessment of cognitive function via the Stroop test

    3. Wisconsin Card Sorting Test (WCST) [From baseline to 10 weeks]

      Pre-post assessment of cognitive function via Wisconsin Card Sorting Test (WCST)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 45 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 The Second Xiangya Hospital of Central South University Changsha China

    Sponsors and Collaborators

    • Central South University

    Investigators

    • Principal Investigator: Wenbin Guo, Central South University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Guo Wenbin, Professor of Psychiatry Department of Psychiatry of the Second Xiangya Hospital, Central South University, Central South University
    ClinicalTrials.gov Identifier:
    NCT05039489
    Other Study ID Numbers:
    • 82171508
    First Posted:
    Sep 9, 2021
    Last Update Posted:
    Mar 11, 2022
    Last Verified:
    Sep 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Guo Wenbin, Professor of Psychiatry Department of Psychiatry of the Second Xiangya Hospital, Central South University, Central South University
    Medication-Resistant Auditory Hallucinations
    Continuous theta burst stimulation，cTBS
    Neuroimaging
    Additional relevant MeSH terms:
    Hallucinations
    Schizophrenia
    Antipsychotic Agents

    Study Results

    No Results Posted as of Mar 11, 2022