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

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Auditory Hallucinations
• Intervention / Treatment: Procedure: Active rTMS x sham (placebo) rTMS; Procedure: (1Hz) rTMS applied over the left temporoparietal cortex; Procedure: sham rTMS

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil
      • Hospital de Clinicas de Porto Alegre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active rTMS; 1Hz rTMS sessions applied to the left temporoparietal cortex of the subjects	Procedure: Active rTMS x sham (placebo) rTMS; 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.; Other Names: EMTr; Procedure: (1Hz) rTMS applied over the left temporoparietal cortex; 20 sessions lasting 20 minutes each of low-frequency (1Hz) rTMS applied over the left temporoparietal cortex (LTPC).
Placebo Comparator: Sham rtms; 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; 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.; Other Names: EMTr; Procedure: sham rTMS; same coil, same number of pulses but using an angled coil(90degres) over the frontotemporal region; Other Names: Sham

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Hospital de Clinicas de Porto Alegre
• Investigators: Principal Investigator: Danilo Jesus, Psychiatrist, Hospital de Clinicas de Porto Alegre; Study Director: Paulo B Abreu, phd, HCPorto Alegre

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: November 10, 2009
• First Submitted That Met QC Criteria: November 16, 2009
• First Posted (Estimate): November 17, 2009

Study Record Updates

• Last Update Posted (Estimate): August 12, 2010
• Last Update Submitted That Met QC Criteria: August 11, 2010
• Last Verified: August 1, 2010

More Information

Terms related to this study

• Keywords: rTMS; auditory hallucinations; refractory schizophrenia
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Schizophrenia Spectrum and Other Psychotic Disorders; Perceptual Disorders; Schizophrenia; Hallucinations
• Other Study ID Numbers: 06382