Efficacy and Safety of Bilateral Theta Burst Stimulation for the Treatment of Auditory Hallucinations

Study Overview
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Brief Summary
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First clinical studies indicate an effect of repetitive transcranial magnetic stimulation(rTMS) in the treatment of auditory hallucinations (AH). However, effect size, optimal stimulation site and parameters are unclear. With this randomized, placebo-controlled clinical trial we test the efficacy and safety of bilateral continuous theta burst stimulation (cTBS), a patterned form rTMS, against auditory hallucinations. The treatment will be applied add-on to individual antipsychotic and behavioral therapy. Patients will be treated for 6 weeks each weekday (30 sessions) with 40s of cTBS (halfway between T3/P3 and T4/P4). For weeks 1-3, half of the subjects will be randomized to a sham-stimulation (coil tilted 45°). During weeks 4-6, all subjects receive real cTBS.

Official Title
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Efficacy and Safety of Bilateral Repetitive Transcranial Magnetic Stimulation (Theta Burst Stimulation) for the Treatment of Auditory Hallucinations

Conditions
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Auditory Hallucinations

Intervention / Treatment
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* Procedure: continuous theta burst stimulation (cTBS)
* Procedure: sham cTBS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: auditory hallucinations at least once a week Schizophrenia (DSM-IV) stable treatment setting (in- or out-patient) no change of antipsychotics during and at least 1 week before treatment initiation Exclusion Criteria: epilepsy benzodiazepines > 1,5mg lorazepam / d pregnancy metal parts in the brain cardiac pacemaker deep brain stimulation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: cTBS<br> | Procedure: continuous theta burst stimulation (cTBS)<br>* bilateral continuous theta burst stimulation (bursts of 3 stimuli, 50Hz every 200ms for 40s, 80% active motor threshold) to the temporoparietal cortex (EEG 10/20: halfway T3/P3 and T4/P4)<br>|
| Sham Comparator: Sham cTBS<br> | Procedure: sham cTBS<br>* bilateral continuous theta burst stimulation (bursts of 3 stimuli, 50Hz every 200ms for 40s, 80% active motor threshold) to the temporoparietal cortex (EEG 10/20: halfway T3/P3 and T4/P4) with the stimulation coil tilted 45°<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Psychotic Symptom Rating Scales (PSYRATS), subscale for auditory hallucinations | Change of PSYRATS AH score compared to baseline after 3 weeks of treatment | 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hallucination change score (HCS) |  | 3 and 6 weeks | 
| Positive and Negative Symptom Scale (PANSS) |  | 3 and 6 weeks | 
| PSYRATS subscale for auditory hallucinations | Change of PSYRATS AH score compared to baseline after 6 weeks of treatment | 6 weeks |