Study of Repetitive Transcranial Magnetic Stimulation in the Treatment of Cognitive Impairment in Schizophrenia

Study Overview
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Brief Summary
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Exploration of repetitive transcranial magnetic stimulation（rTMS）on working memory and cognitive impairment symptoms of schizophrenia treatment and mechanism. Analysis of high-frequency repetitive transcranial magnetic stimulation stimulation to the improvement of negative symptoms and psychotic symptoms.

Detailed Description
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The study was a randomized double-blind sham-controlled trial for 4 weeks. Patients with schizophrenia were treated with 20-Hz rTMS for 4 weeks to the left dorsolateral prefrontal cortex (added to the ongoing treatment). Negative symptoms were assessed with the Scale for the Assessment of Negative Symptoms (SANS), the Positive and Negative symptom scale (PANSS).The auditory steady state responses (ASSR) were obtained for the assessment of gamma oscillation.And cognitive symptoms were assessed by MATRICS cognitive test battery (MCCB) Chinese version and n-back task.

Official Title
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Study of Repetitive Transcranial Magnetic Stimulation in the Treatment of Cognitive Impairment in Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Device: Repetitive Transcranial Magnetic Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1）patients to be diagnosed according to the Fourth Edition of the Diagnostic and Statistical Manual of Mental Disorders(DSM-IV) for paranoid schizophrenia；2）20～49 years old；3）Duration of 2   10 years;4）the disease situation is stable， the fluctuation of Positive and Negative Symptom Scale（PANSS）total score ≤10% in last 1 month, and have accepted the current drugs for more than 8 weeks; 5）Patients, their families and doctors are agreed that the disease situation is stable and maintained current drug treatment in next month；6）Signed an informed consent Exclusion Criteria: 1)patients to be diagnosed according to DSM-IV for substance abused,development delayed;2)suffering from serious physical disease and can not accept the treatment;3)repetitive transcranial magnetic stimulation(rTMS) contraindications: intracranial metal substance, with heart pacemakers and cochlear implants, intracranial pressure;4)the disease situation is not stable， the fluctuation of Positive and Negative Symptom Scale（PANSS）total score >10% in last 1 month, Positive and Negative Symptom Scale（PANSS）total score > 60;5)difficult to maintain the current drug treatment for at least 1 month;6）undergoing electroconvulsive therapy（ECT）in last 3 months.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 49 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active rTMS<br>Active treatment will be delivered at an intensity that is 90% of the resting motor threshold (RMT). Stimulation will be delivered at 20 Hz with 100 stimulation trains of 20 stimuli each (i.e., 2000 stimuli) and an inter-train interval of 9 sec. Treatment will be applied in sequential order to the left dorsolateral prefrontal cortex (DLPFC). Intervention: Device: Repetitive Transcranial Magnetic Stimulation | Device: Repetitive Transcranial Magnetic Stimulation<br>* The MagPro X100 is connected to a Magnetic Coil which transfers the magnetic stimulation to the tissue. The original coils MC-B65 can be used with the MagPro X100.<br>|
| Sham Comparator: Sham rTMS<br>Sham rTMS stimulation will be delivered using the same stimulation parameters and at the site of active treatment, but the coil will be reversed. This method produces sound and some somatic sensation (e.g., contraction of scalp muscles) similar to those of active stimulation, but with minimal direct brain effects.Intervention: Device: Repetitive Transcranial Magnetic Stimulation | Device: Repetitive Transcranial Magnetic Stimulation<br>* The MagPro X100 is connected to a Magnetic Coil which transfers the magnetic stimulation to the tissue. The original coils MC-B65 can be used with the MagPro X100.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Change in the Severity of Negative Symptoms | The assessment of negative symptoms were measured with the Positive and Negative Symptom Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS).The SANS contains 30 particular items divided into 5 symptomatological domains: 1) affective flattening and/or blunting, 2) alogia, 3) avolition and/or apathy, 4) anhedonia, and 5) impaired attention. Each item is scored on a scale from 0 (not at all) to 5 (severe) with a total scoring range of 0 to 150. Higher scores indicate more impairment.The PANSS contains 30 particular items divided into 3 subscores: 1)positive, 2) negative, and 3) general subscore. Each item is scored on a scale from 1 (absent) to 7 (extreme) with a total scoring range of 30 to 210. Higher scores indicate more impairment. The primary outcomes were the changes in the severity of negative symptoms as measured with SANS total score and PANSS negative subscore after 4 weeks of intervention. | Baseline, after 4 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MATRICS Consensus Cognitive Battery (MCCB) in Chinese Version | MCCB in Chinese Version includes 9 tasks across 7 domains, and a composite score, including Processing Speed (Brief Assessment of Cognition in Schizophrenia Symbol Coding, Animal Fluency, Trails A), Attention (Continuous Performance Test), Working Memory (WMS-III Spatial Span), Verbal Learning (Hopkins Verbal Learning Test - Revised), Visual Learning (Brief Visuospatial Memory Test - Revised), Problem Solving (Neuropsychological Assessment Battery), and Social Cognition (Mayer-Salovey- Caruso Emotional Intelligence Test).The results are reported as T scores with a mean of 50 and an SD of 10. | Baseline and 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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schizophrenia