Transcranial Magnetic Stimulation for "Voices"

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Ralph Edward Hoffman, Yale University
ClinicalTrials.gov Identifier:
NCT00308997
First received: March 28, 2006
Last updated: December 13, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Schizophrenia
Hallucinations
Device: 1-hertz Repetitive Transcranial Magnetic Stimulation
Device: Active 1-Hertz Repetitive transcranial magnetic stimulation
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Transcranial Magnetic Stimulation Guided by Neuroimaging for Patients With Persistent "Voices"

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Hallucination Change Score - Right (HCS-right) [ Time Frame: After 5 sessions of rTMS ] [ Designated as safety issue: No ]

    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


  • Hallucination Change Score - Left (HCS-left) [ Time Frame: After 5 sessions of rTMS ] [ Designated as safety issue: No ]

    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


  • Hallucination Change Score (HCS) [ Time Frame: After 15 sessions of rTMS ] [ Designated as safety issue: No ]

    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



Secondary Outcome Measures:
  • Change in Hallucination Frequency [ Time Frame: After 15 sessions of rTMS ] [ Designated as safety issue: No ]

    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.


  • Change in Total Auditory Hall Rating Scale (AHRS) Score [ Time Frame: After 15 sessions of rTMS ] [ Designated as safety issue: No ]

    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.


  • Clinical Global Improvement (CGI)Improvement [ Time Frame: After 15 sessions of rTMS ] [ Designated as safety issue: No ]

    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



Enrollment: 85
Study Start Date: February 2006
Study Completion Date: April 2012
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Magstim Rapid-2

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00308997

Locations
United States, Connecticut
Yale Psychiatric Research
New Haven, Connecticut, United States, 06519
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Ralph E. Hoffman, MD Yale University School of Medicine, Department of Psychiatry
  More Information

Additional Information:
Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ralph Edward Hoffman, Principal Investigator, Yale University
ClinicalTrials.gov Identifier: NCT00308997     History of Changes
Other Study ID Numbers: R01 MH073673-01, R01MH073673-01, DATR A5-ETPD
Study First Received: March 28, 2006
Results First Received: November 14, 2012
Last Updated: December 13, 2012
Health Authority: United States: Federal Government

Keywords provided by Yale University:
Auditory Hallucinations
Schizophrenia
Schizoaffective Disorder
Repetitive Transcranial Magnetic Stimulation
Wernicke's Area
Superior Temporal Gyrus

Additional relevant MeSH terms:
Schizophrenia
Hallucinations
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Perceptual Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms

ClinicalTrials.gov processed this record on October 19, 2014