Transcranial Magnetic Stimulation for "Voices"

March 31, 2020 updated by: Yale University

Transcranial Magnetic Stimulation Guided by Neuroimaging for Patients With Persistent "Voices"

This study will determine the efficacy of MRI-guided transcranial magnetic stimulation (TMS)in reducing "voices" and other symptoms experienced by people with schizophrenia and schizoaffective disorder. In addition, the study will determine duration of improvement obtained during the course of trial participation via on-going monthly contact with study participants for up to 1 year after the trial.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Schizophrenia is a severely disabling brain disorder that affects about 1% of the United States population. Approximately 50 to 80% of people with schizophrenia experience "voices," also known as auditory hallucinations. These hallucinations consist of spoken speech, which sometimes replicates the speaking voice of a familiar person, and sometimes reflects a speaking voice that is not known but becomes highly recognizable. The phrases and sentences expressed by "voices" are often highly disruptive, and may comment, cajole, criticize, and, in some cases, command the patient. They are often but not invariably distressing, and can disrupt one's ability to interact with others, work, study, and sleep. In about 25% of cases, medication treatment is either completely ineffective or only partially effective in relieving "voices." Effective treatment alternatives are needed to improve this troubling and often disabling symptom.

Recent studies have suggested that auditory hallucinations arise from parts of the brain that are ordinarily involved in perceiving actual spoken speech. Low frequency repetitive transcranial magnetic stimulation (rTMS), a technique that uses an electromagnet to induce reductions in cortical brain activity, may therefore be effective in quieting auditory hallucinations. The potential usefulness of this approach has been demonstrated by previous studies conducted at our medical center. This new study uses magnetic resonance imaging (MRI) to locate two areas of the brain involved in speech perception. These areas are in Wernicke's area in the left superior temporal gyrus, and in the right hemisphere in an analogous site in the superior temporal gyrus. Repetitive TMS is specifically positioned to reduce cortical excitability or reactivity at these two brain regions.

Participants in this double blind study will be randomly assigned to receive either real rTMS, or placebo stimulation, which feels similar to real rTMS but does not produce direct brain effects. Depending on group assignment, participation may last 4 to 8 weeks. Over the first 2 weeks, all participants will undergo two sequences of rTMS, each consisting of five 16-minute sessions. One sequence is directed to left Wernicke's area and the other sequence is directed to the right-sided equivalent area. During the third week, participants will receive five additional sessions to the left or right site that appeared to produce greater clinical improvement. All participants will then be informed as to whether they received real or placebo stimulation. Participants who received real stimulation will be offered 5 additional stimulation sessions at the brain site that achieved the best response. Participants who received placebo stimulation will be offered real stimulation for up to twenty sessions over 4 weeks using the same schedule described above. Assessments of severity of hallucinations and other clinical symptoms will be conducted after every fifth rTMS session by a clinician who does not know whether the participant is receiving real or placebo stimulation.

Neuropsychological testing will also be done before, during, and after the trial. Our previous trial demonstrated some improvement in verbal processing with no significant impairments in terms of memory, language or cognitive function. However, insofar as this trial involves a greater total "dose" of rTMS, careful monitoring of these functions is conducted throughout the trial.

In addition, the study will determine the degree to which improvement obtained during the course of trial is sustained over the ensuing months. This is accomplished via on-going monthly contact with study participants for up to 1 year after the last rTMS stimulation session.

Study Type

Interventional

Enrollment (Actual)

85

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06519
        • Yale Psychiatric Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Auditory hallucinations that occur at least five times per day, on average
  • Diagnosis of schizophrenia or schizoaffective disorder

Exclusion Criteria:

  • Pregnant
  • History of seizure that is not drug-induced or secondary to alcohol withdrawal
  • Drug or alcohol abuse within 6 weeks of study entry (prior history of drug or alcohol abuse is not an exclusion)
  • Changes in antipsychotic drug dosages within 4 weeks of study entry (patients do not need to be on antipsychotic medication to be included)
  • Current significant untreated or unstable medical illness (e.g., poorly controlled diabetes mellitus, severe hypertension, unstable cardiac arrhythmia)
  • Inability to understand the nature of the study due to severe psychotic disorganization, mental retardation, etc.
  • Significant neurological condition (e.g., traumatic brain injury, multiple sclerosis)
  • Factors that would preclude an MRI scan (e.g., severe obesity, claustrophobia, certain surgical implants with metallic components, metal shavings in the eye acquired while working as machinist)
  • Cardiac pacemaker

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 1
Active 1-hertz Repetitive Transcranial Magnetic Stimulation to Wernicke's area and right homologous area
Device: Active 1-Hertz Repetitive transcranial magnetic stimulation
Active stimulation given to Wernicke's area or a right homologous area for 16 minutes per day x 5 days for week I, the same for week II with switch from right to left or left to right, and 5 more stimulation sessions (16 minutes per session) to the side producing greater benefit for week III.
Other Names:
  • Magstim Rapid-2
SHAM_COMPARATOR: 2
sham rTMS to Wernicke's area and a right homologous area
Device: 1-hertz Repetitive Transcranial Magnetic Stimulation
Sham stimulation given to Wernicke's area or a right homologous area for 16 minutes per day x 5 days for week I, the same for week II with switch from right to left or left to right, and 5 more stimulation sessions (16 minutes per session) to the side producing greater benefit for week III.
Other Names:
  • Magstim Rapid-2

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hallucination Change Score - Right (HCS-right)
Time Frame: After 5 sessions of rTMS

HCS score for participants assessed after 5 sessions, 16 minutes per session, who received either rTMS or sham stimulation delivered to the right superior temporal gyrus.

HCS was anchored at 0 (corresponding to no AVHs), 10 (no change in hallucination severity) and 20 (AVHs twice as severe as baseline). Lower scores correspond to greater improvement
After 5 sessions of rTMS
Hallucination Change Score - Left (HCS-left)
Time Frame: After 5 sessions of rTMS

HCS score for participants assessed after 5 sessions, 16 minutes per session, who received either rTMS or sham stimulation delivered to the left superior temporal gyrus.

HCS was anchored at 0 (corresponding to no AVHs), 10 (no change in hallucination severity) and 20 (AVHs twice as severe as baseline). Lower scores correspond to greater improvement
After 5 sessions of rTMS
Hallucination Change Score (HCS)
Time Frame: After 15 sessions of rTMS

HCS score assessed after 15 sessions, 16 minutes per session, delivered to both right superior temporal and left superior temporal gyrus sites using either rTMS or sham stimulation. For patients dropping out of the trial prematurely, last-observation-carried-forward data were used for this outcome variable.

HCS was anchored at 0 (corresponding to no AVHs), 10 (no change in hallucination severity) and 20 (AVHs twice as severe as baseline). Lower scores correspond to greater improvement
After 15 sessions of rTMS

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Hallucination Frequency
Time Frame: After 15 sessions of rTMS

AHRS frequency scale score assessed after 15 sessions, 16 minutes per session, of both right superior temporal and left superior temporal gyrus sites using either rTMS or sham stimulation (3 weeks). For patients dropping out of the trial prematurely, last-observation-carried-forward data were used for this outcome variable. The hallucination frequency range is from 0-9. The scores reported are difference scores, and an improvement is a higher score.

Hallucination frequency is one of the variables incorporated into the AHRS (Auditory Hallucinations Rating Scale). The score is measured as change relative to baseline (i.e., baseline minus endpoint). Larger (positive) scores correspond to greater improvement.
After 15 sessions of rTMS
Change in Total Auditory Hall Rating Scale (AHRS) Score
Time Frame: After 15 sessions of rTMS

Total AHRS score assessed after 15 sessions, 16 minutes per session, of both right superior temporal and left superior temporal gyrus sites using either rTMS or sham stimulation (3 weeks). For patients dropping out of the trial prematurely, last-observation-carried-forward data were used for this outcome variable. The score range is from 0-42. This is reported as a difference score and a higher score is an improvement.

Total AHRS score is measured as change relative baseline (i.e., baseline minus endpoint). Larger (positive) scores correspond to greater improvement.
After 15 sessions of rTMS
Clinical Global Improvement (CGI)Improvement
Time Frame: After 15 sessions of rTMS

CGI score assessed after 15 sessions, 16 minutes per session, of both right superior temporal and left superior temporal gyrus sites using either rTMS or sham stimulation (3 weeks). For patients dropping out of the trial prematurely, last-observation-carried-forward data were used for this outcome variable. The range for this score is from 1 to 7.

Lower scores correspond to greater improvement
After 15 sessions of rTMS

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Yale University

Collaborators

National Institute of Mental Health (NIMH)

Investigators

  • Principal Investigator: Ralph E. Hoffman, MD, Yale University School of Medicine, Department of Psychiatry

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2006

Primary Completion (ACTUAL)

September 1, 2011

Study Completion (ACTUAL)

April 1, 2012

Study Registration Dates

First Submitted

March 28, 2006

First Submitted That Met QC Criteria

March 28, 2006

First Posted (ESTIMATE)

March 30, 2006

Study Record Updates

Last Update Posted (ACTUAL)

April 2, 2020

Last Update Submitted That Met QC Criteria

March 31, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0409027023b
  • DATR A5-ETPD
  • R01MH073673-01 (NIH)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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