Deep Transcranial Magnetic Stimulation for the Treatment of Treatment Resistance Schizophrenia

Study Overview
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Brief Summary
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Based on the hypothesis that low-frequency deep transcranial magnetic stimulation(dTMS) on anterior cingulate cortex （ACC） could down-regulate the glutamate level of ACC and regulate the acc-related functional network in patients with treatment resistance schizophrenia,this research plan to utilise multimodal functional magnetic imaging method(including structural MRI,resting-state functional magnetic resonance imaging and 1H-MRS) to investigate therapeutic efficacy of low-frequency deep transcranial magnetic stimulation on SZ patients symptoms,as well as to elucidate the correlation between treatment effects and glutamate level of ACC

Detailed Description
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This study includes 20 treatment resistance schizophrenia patients and 20 healthy controls.This study will investigate 1)abnormalities of the glutamate level of ACC in patients with schizophrenia compared to healthy controls by using 1H-MRS technique. 2)potential modulation effects of deep transcranial magnetic stimulation(dTMS) on anterior cingulate cortex function of patients with schizophrenia. 3)the therapeutic efficacy of dTMS on cognitive impairments and other psychotic symptoms of patients with schizophrenia by adopting cognitive function and psychotic symptoms evaluation,as well as to explore the optimal dTMS treatment pattern on cognitive function.

Official Title
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Deep Transcranial Magnetic Stimulation for the Treatment of Treatment Resistance Schizophrenia: a Double-Blind, Randomized Clinical Trial

Conditions
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Deep Transcranial Magnetic Stimulation for the Treatment of Treatment Resistance Schizophrenia

Intervention / Treatment
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* Device: deep transcranial magnetic stimulation with H7 coil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with schizophrenia who meet the dsm-5 diagnostic criteria Aged from 18 to 60 After 4 weeks of treatment with a sufficient dose of an antipsychotic (equivalent dose of 400   600 mg/ day chlorpromazine (CPZ)), no clinical improvement was achieved (at least two items in PANSS scale P1,P2,P3,N1,N4,N6,G5 and G9 ≥4 points, or cgi-s ≥4 points) Right-handedness, normal hearing, visual acuity or corrected visual acuity Written informed consent of the patient and his/her family Exclusion Criteria: Patients who are currently taking clozapine or who have failed to respond to a full course of treatment with clozapine Current or past neurological illness,severe physical illness,substance abuse or addiction,alcohol dependence,mental retardation,pregnancy or lactation,extreme agitation, stupor, negative suicide,or those who can not cooperate A history of MECT within 6 months,or those with contraindications to MRI,rTMS Medically unstable for at least 1 month (PANSS score fluctuation>10%)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: In this research,we combine a cross-sectional case control study and a randomized controlled study.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: sham stimulation<br>20 patients will be randomly allocated into this group,they will receive sham stimulation. | Device: deep transcranial magnetic stimulation with H7 coil<br>* low frequency(1Hz) deep transcranial magnetic stimulation on ACC .Duration:20 days.<br>|
| Active Comparator: real stimulation dTMS targeting the ACC<br>20 patients will be randomly allocated into this group,they will receive real stimulation. | Device: deep transcranial magnetic stimulation with H7 coil<br>* low frequency(1Hz) deep transcranial magnetic stimulation on ACC .Duration:20 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Positive and Negative Syndrome Scale(PANSS) | Change from baseline in Positive and Negative Syndrome Scale(PANSS) after dtms treat 30 days | baseline,24 hours after the dTMS treatment,30 days | 
| Change from baseline in MATRICS Consensus Cognitive Battery | MATRICS Consensus Cognitive Battery | baseline,24 hours after the rTMS treatment,30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of ACC neurogenesis | Quantify neural stem cells in hippocampal by using H1-MRS | baseline,24 hours after the dTMS treatment | 
| Change in glutamate level |  | baseline,24 hours after the dTMS treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment Resistance Schizophrenia, Deep Transcranial Magnetic Stimulation, anterior cingulate cortex, glutamate, H7 coil