Navigated αTMS in Treatment-resistant Schizophrenia

Study Overview
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Brief Summary
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Since 1990s, stimulation of prefrontal cortex (PFC) has shown therapeutic effects on auditory hallucinations as well as negative symptoms of schizophrenia. However, previous studies have reported mixed or negative results. Majority of the repetitive transcranial magnetic stimulation (rTMS) studies to date has set the target of cortical stimulation based on scalp site. Recently introduced method, navigated transcranial magnetic stimulation (nTMS) integrates the individual MRI data, and thus allows more precise targeting on brain cortical regions enhancing the efficacy of rTMS. Previous EEG studies have suggested reduced alpha band activity in patients with schizophrenia. Some recent studies using alpha (α) EEG guided TMS for treating positive and negative symptoms of schizophrenia have demonstrated promising results. The aim of the study is to investigate the efficacy of navigated individualized αTMS in treatment-resistant patients with schizophrenia. Approximately fifty patients with DSM-IV schizophrenia will be enrolled in this randomized, double-blind, sham-controlled study. The patients will receive 13 - 15 session of αTMS to the left dorsolateral prefrontal cortex (DLPFC), as adjunctive therapy, for 3 weeks. We assess patients via the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression (CGI) and neurocognitive test battery at baseline, 5 days after and 3 months after treatment. Serum and plasma levels of brain derived neurotrophic factor (BDNF) are assayed at pre and post treatment weeks.

Official Title
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Navigated Alpha Frequency Transcranial Magnetic Stimulation (αTMS) in Treatment-resistant Schizophrenia

Conditions
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Schizophrenia, Schizoaffective Disorder

Intervention / Treatment
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* Device: navigated Transcranial Magnetic Stimulation
* Device: navigated Transcranial Magnetic Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male righthanded inpatients, 18 to 64 years of age The diagnosis of Schizophrenia or Schizoaffective Disorder according to DSM-IV Capacity and willingness to give informed consent Patient is treatment-resistant, CGI-S 4 or more Patient is not requiring a change in antipsychotic medication 2 weeks prior to or during treatment No foreseeable changes in patient's smoking habits during treatment Exclusion Criteria: Serious somatic illness Progressive neurological illness, recent brain damage (less than 3 months ago) or sequela of serious brain damage Unstable epilepsy Electro convulsive therapy (ECT) less than 3 months prior to treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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Male

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Navigated individualized αTMS<br>navigated Transcranial Magnetic Stimulation | Device: navigated Transcranial Magnetic Stimulation<br>* individualized α frequency left DLPFC 110% motor threshold (MT) 13-15 sessions for 3 weeks<br>* Other names: rTMS;|
| Sham Comparator: Sham TMS<br>navigated Transcranial Magnetic Stimulation using sham coil | Device: navigated Transcranial Magnetic Stimulation<br>* - placebo treatment: sham coil<br>* Other names: rTMS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive and Negative Syndrome Scale (PANSS) | change in PANSS total, positive, negative and general psychopathology sum score | at baseline,5 days after treatment, 3 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression - Improvement scale (CGI-I) | change in patient's illness relative to baseline state | at 5 days after treatment, 3 months after treatment | 
| Neuropsychology test battery | Neuropsychology test battery consists of 6 tests for measuring neurocognitive function. | at baseline, 5 days after treatment, 3 months after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transcranial Magnetic Stimulation, Repetitive Transcranial Magnetic Stimulation, Schizophrenia, Schizoaffective Disorder, Treatment, Negative Symptoms, Positive Symptoms, TMS, rTMS