SchizophreniaNCT05039489
A Study on the Brain Mechanism of cTBS in Improving Medication-resistant Auditory Hallucinations in Schizophrenia
A study testing Antipsychotic drugs, cTBS（the left temporoparietal cortex as the stimulation target） and cTBS （the left cerebellum Crus II as the stimulation target） in people with Schizophrenia, run by Central South University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Antipsychotic drugs, cTBS（the left temporoparietal cortex as the stimulation target） and cTBS （the left cerebellum Crus II as the stimulation target）
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteChina
- Study dates
- 9 Sep 2021to 30 Nov 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Schizophrenia
- Being tested
- Antipsychotic drugs, cTBS（the left temporoparietal cortex as the stimulation target）, cTBS （the left cerebellum Crus II as the stimulation target）
- Keywords
- Medication-Resistant Auditory Hallucinations, Continuous theta burst stimulation，cTBS, Neuroimaging
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Antipsychotic drugsDrug
Also called MRI scan
Stable antipsychotic medication 4 weeks before and during the treatment. Chlorpromazine (CPZ) equivalent dosages were calculated for second- and first-generation antipsychotic drugs
cTBS（the left temporoparietal cortex as the stimulation target）Device
Also called MRI scan
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
cTBS （the left cerebellum Crus II as the stimulation target）Device
Also called MRI scan
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
| Study group | Role | What they receive |
|---|---|---|
| The schizophrenia patients with medication-resistant auditory hallucinations | Experimental | Drug + cTBS intervention (the left cerebellum Crus II as the stimulation target) Receives: Drug: Antipsychotic drugs; Device: cTBS （the left cerebellum Crus II as the stimulation target） |
| The schizophrenia patients with general auditory hallucinations | Active comparator | Drug intervention Receives: Drug: Antipsychotic drugs |
| The healthy controls | No intervention | MRI scan at baseline and no drugs treatment |
| Drug + cTBS intervention: the first-episode schizophrenia patients with auditory hallucinations | Experimental | Drug + cTBS intervention (the left temporoparietal cortex as the stimulation target) Receives: Drug: Antipsychotic drugs; Device: cTBS（the left temporoparietal cortex as the stimulation target） |
| Drug intervention: the first-episode schizophrenia patients with auditory hallucinations | Active comparator | Drug intervention Receives: Drug: Antipsychotic drugs |
| The schizophrenia patients with medication-resistant auditory hallucinations from the fourth arm | Experimental | Drug + cTBS intervention (the left cerebellum Crus II as the stimulation target) Receives: Drug: Antipsychotic drugs; Device: cTBS （the left cerebellum Crus II as the stimulation target） |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From baseline to 10 weeks
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.
Measured: From baseline to 10 weeks
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.
Measured: From baseline to 10 weeks
Secondary outcomes (3)
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)
Measured: From baseline to 10 weeks
The Stroop test
Pre-post assessment of cognitive function via the Stroop test
Measured: From baseline to 10 weeks
Wisconsin Card Sorting Test (WCST)
Pre-post assessment of cognitive function via Wisconsin Card Sorting Test (WCST)
Measured: From baseline to 10 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2021
- Study start9 Sep 2021
- Primary completion31 Oct 2023
- Study completion30 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- Central South University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Guo Wenbin, Central South University
- Investigators
- Wenbin Guo, Principal investigator, Central South University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05039489
- Sponsor's protocol ID
- 82171508
- Status last verified
- Aug 2024
- First submitted
- 31 Aug 2021
- Last updated
- 21 Aug 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study on the Brain Mechanism of cTBS in Improving Medication-resistant Auditory Hallucinations in Schizophrenia
- ClinicalTrials.gov ID
- NCT05039489
- Acronym / sponsor ID
- 82171508
- Conditions
- Schizophrenia
- Keywords
- Medication-Resistant Auditory Hallucinations, Continuous theta burst stimulation，cTBS, Neuroimaging
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- Central South UniversityUniversity, hospital or other
- Study start
- 9 Sep 2021 (actual)
- Primary completion
- 31 Oct 2023 (actual)
- Study completion
- 30 Nov 2023 (actual)
- First posted
- 9 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| The schizophrenia patients with medication-resistant auditory hallucinations | Experimental | Drug: Antipsychotic drugs, Device: cTBS （the left cerebellum Crus II as the stimulation target）Drug + cTBS intervention (the left cerebellum Crus II as the stimulation target) |
| The schizophrenia patients with general auditory hallucinations | Active comparator | Drug: Antipsychotic drugsDrug intervention |
| The healthy controls | No intervention | –MRI scan at baseline and no drugs treatment |
| Drug + cTBS intervention: the first-episode schizophrenia patients with auditory hallucinations | Experimental | Drug: Antipsychotic drugs, Device: cTBS（the left temporoparietal cortex as the stimulation target）Drug + cTBS intervention (the left temporoparietal cortex as the stimulation target) |
| Drug intervention: the first-episode schizophrenia patients with auditory hallucinations | Active comparator | Drug: Antipsychotic drugsDrug intervention |
| The schizophrenia patients with medication-resistant auditory hallucinations from the fourth arm | Experimental | Drug: Antipsychotic drugs, Device: cTBS （the left cerebellum Crus II as the stimulation target）Drug + cTBS intervention (the left cerebellum Crus II as the stimulation target) |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Antipsychotic drugsAlso: MRI scanStable antipsychotic medication 4 weeks before and during the treatment. Chlorpromazine (CPZ) equivalent dosages were calculated for second- and first-generation antipsychotic drugs | Drug | 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 general auditory hallucinations, The schizophrenia patients with medication-resistant auditory hallucinations, The schizophrenia patients with medication-resistant auditory hallucinations from the fourth arm |
| cTBS（the left temporoparietal cortex as the stimulation target）Also: MRI scanParticipants 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 | Device | Drug + cTBS intervention: the first-episode schizophrenia patients with auditory hallucinations |
| cTBS （the left cerebellum Crus II as the stimulation target）Also: MRI scanParticipants 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 | Device | The schizophrenia patients with medication-resistant auditory hallucinations, The schizophrenia patients with medication-resistant auditory hallucinations from the fourth arm |
Primary outcome
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.
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.
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.
3 secondary outcomes
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
Time frame: From baseline to 10 weeks
The Stroop test
Time frame: From baseline to 10 weeks
Wisconsin Card Sorting Test (WCST)
Time frame: From baseline to 10 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wenbin Guo principal investigator
Central South University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Antipsychotic drugs, cTBS（the left temporoparietal cortex as the stimulation target） and cTBS （the left cerebellum Crus II as the stimulation target） in people with Schizophrenia, run by Central South University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Psychotic Symptom Rating Scales-Auditory Hallucination Subscale (PSYRATS-AH) (time frame: From baseline to 10 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2024.