Repetitive Transcranial Magnetic Stimulation for "Voices"

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

OBJECTIVES:

I. Determine the effect of repetitive transcranial magnetic stimulation on treatment refractory auditory hallucinations of patients with schizophrenia.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Device: repetitive transcranial magnetic stimulation (rTMS); Device: sham stimulation

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520-8099
      • Yale University School Of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: active rTMS; 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); a total of 132 minutes of stimulation at one hertz, motor threshold set at 80%, delivered to TP3 scalp site; Other Names: MATSTIM SUPER RAPID
Placebo Comparator: sham stimulation; Sham stimulation delivered 16 minutes per session given one session per day for nine consecutive days (with the exception of weekends)	Device: sham stimulation; 132 minutes of stimulation given at 80% motor threshold with coil tilted "single wing" 45 degrees away from scalp deliverd to TP3 site; Other Names: MAGSTIM SUPER RAPID

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Study Chair: Ralph Hoffman, Yale University

Publications and helpful links

General Publications

• Hoffman RE, Gueorguieva R, Hawkins KA, Varanko M, Boutros NN, Wu YT, Carroll K, Krystal JH. Temporoparietal transcranial magnetic stimulation for auditory hallucinations: safety, efficacy and moderators in a fifty patient sample. Biol Psychiatry. 2005 Jul 15;58(2):97-104. doi: 10.1016/j.biopsych.2005.03.041.

Helpful Links

• Click here for the Yale School of Medicine Web site describing current, on-going rTMS trial for auditory hallucinations

Study record dates

Study Major Dates

• Study Start: December 1, 1999
• Primary Completion (Actual): January 1, 2005
• Study Completion (Actual): June 1, 2005

Study Registration Dates

• First Submitted: March 10, 2000
• First Submitted That Met QC Criteria: March 10, 2000
• First Posted (Estimate): March 13, 2000

Study Record Updates

• Last Update Posted (Estimate): August 7, 2013
• Last Update Submitted That Met QC Criteria: August 5, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: schizophrenia; neurologic and psychiatric disorders; rare disease
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: R21MH063326 (U.S. NIH Grant/Contract); YALESM-9281; 199/14809; A5-ETPD