Repetitive Transcranial Magnetic Stimulation for Voices

Study Overview
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Brief Summary
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OBJECTIVES: I. Determine the effect of repetitive transcranial magnetic stimulation on treatment refractory auditory hallucinations of patients with schizophrenia.

Detailed Description
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PROTOCOL OUTLINE: This is a randomized, double blind study. Patients are randomized to one of two treatment arms. Group I: Patients receive 9 sessions of active transcranial magnetic stimulation (rTMS) which consists of 8 minutes of rTMS during session 1, 12 minutes duration during session 2, and 16 minutes duration during sessions 3-9. The total duration of stimulation is 132 minutes. Each session was given on a separate day and in general each session occurred on consecutive days with the exception of weekends. Group II: Patients receive 9 sessions of sham stimulation, which consists of 8 minutes of sham stimulation during session 1, 12 minutes duration sham stimulation during session 2, and 16 minutes duration sham stimulation during sessions 3-9. The total duration of sham stimulation is 132 minutes. Each session was given conducted on a separate day and in general each session occured on consecutive days with the exception of weekends. This study provided pilot data supplying the basis for our current study - NCT00308997 -- see our website for details

Official Title
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Repetitive Transcranial Magnetic Stimulation of Speech Processing Brain Areas in Schizophrenic Patients Who Hear Voices

Conditions
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Schizophrenia

Intervention / Treatment
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* Device: repetitive transcranial magnetic stimulation (rTMS)
* Device: sham stimulation


Participation Criteria
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Eligibility Criteria
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PROTOCOL ENTRY CRITERIA: Inclusion criteria: Diagnosis of schizophrenia or schizoaffective disorder based on DSM-IV version of SCID Auditory hallucinations of spoken speech occurring at least 5 times per day where subject able to discern verbal content Right-handed At least 4 weeks on stable antipsychotic medication Exclusion criteria: history of seizure (unless due to drug withdrawal or medication that is no longer prescribed) history of epilepsy in first degree relatives estimated IQ less than 80 unable to provide informed consent significant unstable medical condition current treatment with clozapine or bupropion cochlear implants or other metal in the head (surgical, etc.) history of cardiac arrhythmia cardiac pacemaker active drug or alcohol abuse within prior 6 weeks pregnancy

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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: active rTMS<br>1-Hz rTMS delivered to left temporoparietal cortex at 90% motor threshold for 16 minutes per session given one session per day for nine consecutive days (with the exception of weekends) | Device: repetitive transcranial magnetic stimulation (rTMS)<br>* a total of 132 minutes of stimulation at one hertz, motor threshold set at 80%, delivered to TP3 scalp site<br>* Other names: MATSTIM SUPER RAPID;|
| Placebo Comparator: sham stimulation<br>Sham stimulation delivered 16 minutes per session given one session per day for nine consecutive days (with the exception of weekends) | Device: sham stimulation<br>* 132 minutes of stimulation given at 80% motor threshold with coil tilted single wing 45 degrees away from scalp deliverd to TP3 site<br>* Other names: MAGSTIM SUPER RAPID;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hallucination Change Score (HCS) After 9 Active/Sham rTMS Sessions | Change in hallucination severity relative to baseline with scores ranging 1 in unit intervals to 20 anchored as follows: 0=hallucinations stopped, 10=no change, 20=hallucinations twice as severe as baseline | After the 9th active/sham rTMS session (up to 2 weeks or end of intervention) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hallucination Frequency After 9 Active/Shame rTMS Sessions | Difference between baseline hallucination frequency and hallucintion frequency at last assessment. Assessed on the basis of a 0-9 scale, with higher scores being more severe. | After the 9th active/sham rTMS session (up to 2 weeks or end of intervention) | 
| Clinical Global Improvement (CGI) Scale After 9 Active/Shame rTMS Sessions | Scaled from 1-7 as follows: 1=dramatically improved, 2=moderately improved, 3=minimally improved, 4=no change, 5=minimally worsened, 6=moderately worsened, 7=dramatically worsened | After the 9th active/sham rTMS session (up to 2 weeks or end of intervention) | 
| Responder Status | Responder defined as a participant who attains an endpoint hallucination change score (HCS) of 5 or lower after 9 active/shame rTMS sessions. Change in hallucination severity relative to baseline with scores ranging 1 in unit intervals to 20 anchored as follows: 0=hallucinations stopped, 10=no change, 20=hallucinations twice as severe as baseline | After the 9th active/sham rTMS session (up to 2 weeks or end of intervention) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neurologic and psychiatric disorders, rare disease, schizophrenia