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

Primary Purpose

Schizophrenia

Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Antipsychotic drugs
cTBS(the left temporoparietal cortex as the stimulation target)
cTBS (the left cerebellum Crus II as the stimulation target)
Sponsored by
Central South University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Schizophrenia focused on measuring Medication-Resistant Auditory Hallucinations, Continuous theta burst stimulation,cTBS, Neuroimaging

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • The Second Xiangya Hospital of Central South UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Active Comparator

No Intervention

Experimental

Active Comparator

Experimental

Arm Label

The schizophrenia patients with medication-resistant auditory hallucinations

The schizophrenia patients with general auditory hallucinations

The healthy controls

Drug + cTBS intervention: the first-episode schizophrenia patients with auditory hallucinations

Drug intervention: the first-episode schizophrenia patients with auditory hallucinations

The schizophrenia patients with medication-resistant auditory hallucinations from the fourth arm

Arm Description

Drug + cTBS intervention (the left cerebellum Crus II as the stimulation target)

Drug intervention

MRI scan at baseline and no drugs treatment

Drug + cTBS intervention (the left temporoparietal cortex as the stimulation target)

Drug intervention

Drug + cTBS intervention (the left cerebellum Crus II as the stimulation target)

Outcomes

Primary Outcome Measures

Psychotic Symptom Rating Scales-Auditory Hallucination Subscale (PSYRATS-AH)
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.
Structural and Function MRI data
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.
Positive and Negative Syndrome Scale (PANSS)
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

Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
Pre-post assessment of cognitive function via Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
The Stroop test
Pre-post assessment of cognitive function via the Stroop test
Wisconsin Card Sorting Test (WCST)
Pre-post assessment of cognitive function via Wisconsin Card Sorting Test (WCST)

Full Information

First Posted
August 31, 2021
Last Updated
March 10, 2022
Sponsor
Central South University
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1. Study Identification

Unique Protocol Identification Number
NCT05039489
Brief Title
A Study on the Brain Mechanism of cTBS in Improving Medication-resistant Auditory Hallucinations in Schizophrenia
Official Title
A Study on the Brain Mechanism of cTBS in Improving Medication-resistant Auditory Hallucinations in Schizophrenia
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Recruiting
Study Start Date
September 9, 2021 (Actual)
Primary Completion Date
October 31, 2023 (Anticipated)
Study Completion Date
November 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Central South University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia
Keywords
Medication-Resistant Auditory Hallucinations, Continuous theta burst stimulation,cTBS, Neuroimaging

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
The schizophrenia patients with medication-resistant auditory hallucinations
Arm Type
Experimental
Arm Description
Drug + cTBS intervention (the left cerebellum Crus II as the stimulation target)
Arm Title
The schizophrenia patients with general auditory hallucinations
Arm Type
Active Comparator
Arm Description
Drug intervention
Arm Title
The healthy controls
Arm Type
No Intervention
Arm Description
MRI scan at baseline and no drugs treatment
Arm Title
Drug + cTBS intervention: the first-episode schizophrenia patients with auditory hallucinations
Arm Type
Experimental
Arm Description
Drug + cTBS intervention (the left temporoparietal cortex as the stimulation target)
Arm Title
Drug intervention: the first-episode schizophrenia patients with auditory hallucinations
Arm Type
Active Comparator
Arm Description
Drug intervention
Arm Title
The schizophrenia patients with medication-resistant auditory hallucinations from the fourth arm
Arm Type
Experimental
Arm Description
Drug + cTBS intervention (the left cerebellum Crus II as the stimulation target)
Intervention Type
Drug
Intervention Name(s)
Antipsychotic drugs
Other Intervention Name(s)
MRI scan
Intervention Description
Stable antipsychotic medication 4 weeks before and during the treatment. Chlorpromazine (CPZ) equivalent dosages were calculated for second- and first-generation antipsychotic drugs
Intervention Type
Device
Intervention Name(s)
cTBS(the left temporoparietal cortex as the stimulation target)
Other Intervention Name(s)
MRI scan
Intervention Description
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
Intervention Type
Device
Intervention Name(s)
cTBS (the left cerebellum Crus II as the stimulation target)
Other Intervention Name(s)
MRI scan
Intervention Description
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
Primary Outcome Measure Information:
Title
Psychotic Symptom Rating Scales-Auditory Hallucination Subscale (PSYRATS-AH)
Description
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.
Time Frame
From baseline to 10 weeks
Title
Structural and Function MRI data
Description
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.
Time Frame
From baseline to 10 weeks
Title
Positive and Negative Syndrome Scale (PANSS)
Description
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.
Time Frame
From baseline to 10 weeks
Secondary Outcome Measure Information:
Title
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
Description
Pre-post assessment of cognitive function via Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
Time Frame
From baseline to 10 weeks
Title
The Stroop test
Description
Pre-post assessment of cognitive function via the Stroop test
Time Frame
From baseline to 10 weeks
Title
Wisconsin Card Sorting Test (WCST)
Description
Pre-post assessment of cognitive function via Wisconsin Card Sorting Test (WCST)
Time Frame
From baseline to 10 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Written informed consent 18-45 years old, right-handed Meet the diagnostic criteria for schizophrenia according to the Structural Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) 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 Stable antipsychotic medication 4 weeks before and during the treatment (except auditory hallucination symptoms) Exclusion Criteria: A history of epilepsy, convulsions, stroke or other serious brain diseases There are serious infectious diseases, malignant tumors, and severe somatic comorbidity Mental retardation, personality disorder and so on Contraindications for magnetic resonance imaging Diagnose of substance dependence or abuse as primary clinical problem Pregnancy Participants had received Modified Electraconvulsive Therapy (MECT) or TMS treatment in recent 6 months
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wenbin Guo
Phone
+8613875936768
Email
guowenbin76@csu.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wenbin Guo
Organizational Affiliation
Central South University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Second Xiangya Hospital of Central South University
City
Changsha
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wenbin Guo, professor
Email
guowenbin76@csu.edu.cn

12. IPD Sharing Statement

Learn more about this trial

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

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