A Pilot Double-blind Sham-controlled Trial of Repetitive Transcranial Magnetic Stimulation for Patients With Refractory Schizophrenia Treated With Clozapine

Study Overview
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Brief Summary
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The primary outcome of this study is to evaluate the effects of low frequency subthreshold repetitive Transcranial Magnetic Stimulation applied to the left temporoparietal cortex of patients with refractory schizophrenia on the severity of auditory hallucinations. The secondary outcome is to evaluate the effects of the same rTMS protocol on quality of life, functionality and general psychopathology.

Detailed Description
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Seventeen patients with DSM-IV TR diagnosis of schizophrenia were randomized in two groups. First group received 20 sessions of 20 minutes each of low-frequency (1Hz) rTMS applied over the left temporoparietal cortex (LTPC). Second group received sham (placebo) stimulation over the LTPC for the same period of time. All patients were considered as having refractory schizophrenia and in use of at least 400mg/day of clozapine and refering auditory hallucinations occuring at least 5 times a day.

Official Title
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A Pilot Double-blind Sham-controlled Trial of Repetitive Transcranial Magnetic Stimulation for Patients With Refractory Schizophrenia Treated With Clozapine

Conditions
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Schizophrenia, Auditory Hallucinations

Intervention / Treatment
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* Procedure: Active rTMS x sham (placebo) rTMS
* Procedure: sham rTMS
* Procedure: (1Hz) rTMS applied over the left temporoparietal cortex


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with DSM IV TR diagnose of schizophrenia with treatment-resistant auditory hallucinations. Use of at least 400mg/day of clozapine Men and women from 18 to 65 years old Fertile women must be using adequate contraceptive method BPRS score of at least 27 Exclusion Criteria: Suicide risk Patients with epilepsy, brain surgery and/or head trauma in the past, use of cardiac pace maker or metalic clip in the head Diagnose of substance abuse/dependance Severe uncontrolled organic disease that may interfere in the patient´s participation in the study Any other reason that, in the investigator´s opinion, might interfere with the patient´s participation in the study, such as non compliance.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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>1Hz rTMS sessions applied to the left temporoparietal cortex of the subjects | Procedure: Active rTMS x sham (placebo) rTMS<br>* Seventeen right-handed patients with DSM-IV TR diagnosis of schizophrenia were randomized in two groups. One arm received 20 sessions of 20 minutes each of low-frequency (1Hz) rTMS applied over the left temporoparietal cortex (LTPC). The other arm received sham (placebo) stimulation over the LTPC for the same period of time. All patients were considered as having refractory schizophrenia and in use of at least 400mg/day of clozapine and referred auditory hallucinations.<br>* Other names: EMTr;Procedure: (1Hz) rTMS applied over the left temporoparietal cortex<br>* 20 sessions lasting 20 minutes each of low-frequency (1Hz) rTMS applied over the left temporoparietal cortex (LTPC).<br>|
| Placebo Comparator: Sham rtms<br>Same number of pulses but applied with and angled coil (90 degrees) and placed over the fronto´temporal region | Procedure: Active rTMS x sham (placebo) rTMS<br>* Seventeen right-handed patients with DSM-IV TR diagnosis of schizophrenia were randomized in two groups. One arm received 20 sessions of 20 minutes each of low-frequency (1Hz) rTMS applied over the left temporoparietal cortex (LTPC). The other arm received sham (placebo) stimulation over the LTPC for the same period of time. All patients were considered as having refractory schizophrenia and in use of at least 400mg/day of clozapine and referred auditory hallucinations.<br>* Other names: EMTr;Procedure: sham rTMS<br>* same coil, same number of pulses but using an angled coil(90degres) over the frontotemporal region<br>* Other names: Sham;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the effects of low frequency repetitive Transcranial Magnetic Stimulation applied over the left temporoparietal cortex of refractory schizophrenic patients on the severity of auditory hallucinations. |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The secondary outcomes are to evaluate the effects of the same rTMS protocol on their quality of life, functionality and general psychopathology. |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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refractory schizophrenia, rTMS, auditory hallucinations