TMS in Treatment of Schizophrenia Negative Symptoms

Study Overview
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Brief Summary
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Primary objective: to examine the efficacy and safety of high frequency repetitive transcranial magnetic stimulation (HF rTMS) with H7-coil applied once daily during the twenty days, augmentative to the standard antipsychotic pharmacotherapy and other treatment of negative symptoms in schizophrenia. Targeted population: patients diagnosed with schizophrenia, 18-55 years old with predominant negative symptoms, stable condition for >3 months and unchanged antipsychotic therapy for >1 months and no treatment with antidepressants. Study design: industry independent, multicenter, prospective randomized sham-controlled, two-arms, triple-blind superiority clinical trial with concealed allocation and masked independent outcome assessment. Primary outcome: adjusted median of differences in total SANS score. Adjustment for age, gender, baseline total SANS score, duration of the disorder, and antipsychotic therapy.

Official Title
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Efficacy and Safety of High-frequency Repetitive Transcranial Magnetic Stimulation With H7-coil in the Treatment of Schizophrenia Negative Symptoms; A Multicenter, Randomized, Sham Controlled, Triple Blind Trial

Conditions
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Schizophrenia

Intervention / Treatment
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* Device: HR rTMS
* Device: sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmation diagnosis of schizophrenia (ICD-10 F20) using the Mini-International Neuropsychiatric Interview (MINI) (Lecrubier et al., 1997; Sheehan et al., 1998), Age 18-55 years, Both genders, PANSS negative symptoms subscale score >24, PANSS positive symptoms subscale score <20, Stable condition (no acute psychosis exacerbation, no psychiatric hospitalization because of relapse or worsening of symptoms) during at least three months, Stable antipsychotic therapy with no change of drugs or doses during the one months before the enrollment. Exclusion Criteria: Antipsychotics dose change or change of antipsychotic drug, Hospitalization for somatic illness in another institution, Termination of treatment in a Psychiatric Hospital Sveti Ivan, Pregnancy, Missed more than three consecutive interventions, Withdrawal of consent to participate for the sake of intolerance of TMS or for other reasons.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HR rTMS H7-coil intervention group<br> | Device: HR rTMS<br>* high frequency repetitive transcranial magnetic stimulation (HF rTMS) with H7-coil applied once daily during the twenty days<br>|
| Sham Comparator: sham control group<br> | Device: sham<br>* SHAM HF rTMS coil once daily x 20 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted median of differences in total SANS score | Adjusted median of differences in total SANS score (Andreasen, 1989). We will adjust the medians for age, gender, baseline total SANS score, duration of the disorder, and antipsychotic therapy | assessed up to 20 days of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in SNS score | Change in Self-Evaluation of Negative Symptoms Scale (SNS) (Dollfus, Mach and Morello, 2016) | assessed up to 20 days of treatment | 
| Change of BNSS score | Change in Brief Negative Symptom Scale (BNSS), (Kirkpatrick et al., 2006) | assessed up to 20 days of treatment | 
| Change in PANSS negative symptom subscale with items rescaled to 0-6 range | Change in PANSS negative symptoms subscale with items rescaled to 0-6 range, (Kay, Fiszbein and Opler, 1987) | assessed up to 20 days of treatment | 
| Change in CDSS score | Change in depressive symptoms measured using Calgary Depression Scale for Schizophrenia (CDSS) (Addington, Addington and Schissel, 1990) | assessed up to 20 days of treatment |