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Bilateral Repetitive Transcranial Magnetic Stimulation for Auditory Hallucinations

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Yale University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Yale University
ClinicalTrials.gov Identifier:
NCT00567281
First received: December 3, 2007
Last updated: June 26, 2014
Last verified: June 2014
  Purpose

This trial is designed to determine if administering repetitive transcranial magnetic stimulation (rTMS) simultaneously to two sites in the temporal lobes, one on the left and one on the right, produces greater improvements in "voices" and other symptoms of schizophrenia compared to rTMS given to just one site in the temporal lobes.


Condition Intervention Phase
Schizophrenia
Device: Magstim Rapid 2 system triggering Magstim Super Rapid system
Device: Magstim Rapid-2 system triggering Magstim Super Rapid system
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: Bilateral rTMS Clinical Trial for Persistent Auditory Hallucinations

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Hallucination change score [ Time Frame: Measured at every week ] [ Designated as safety issue: No ]
  • Clinical Global Improvement Scale [ Time Frame: Measured at every week ] [ Designated as safety issue: No ]
  • Frequency subscale of Auditory Hallucinations Rating Scale [ Time Frame: Measured at baseline and every week ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Summed scores of Auditory Hallucination Rating Scale [ Time Frame: Measured at baseline and every week ] [ Designated as safety issue: No ]
  • PANSS composite positive symptoms scale [ Time Frame: Measured at baseline and every week ] [ Designated as safety issue: No ]
  • PANSS composite negative symptom scale [ Time Frame: Measured at baseline and every week ] [ Designated as safety issue: No ]
  • PANSS total score [ Time Frame: Measured at baseline and every week ] [ Designated as safety issue: No ]
  • California Verbal Learning Test (CVLT) [ Time Frame: Measure at baseline and after Week 4 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 40
Study Start Date: October 2007
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Active bilateral rTMS to left/right Wernicke's area and opposite side middle temporal gyrus
Device: Magstim Rapid 2 system triggering Magstim Super Rapid system
Week 1 treatment includes rTMS for 5 sessions to either to left or right Wernicke's area (BA22) synchronous with rTMS to opposite hemisphere middle temporal cortex (BA21). Week 2 treatment includes rTMS given for 5 sessions with positions reversed (e.g., if Wernicke's stimulation was on the left during Week 1, position of rTMS will switch to the right side during Week 2 and vice-versa). As in Week 1, active rTMS will also be given synchronously to the opposite hemisphere middle temporal cortex. Weeks 3 and 4 include 10 stimulation sessions to the configuration of sites producing greater improvement in comparing results of Week 1 and Week 2. rTMS for each stimulation session will be given at 1-Hertz (once per second) for 16 minutes without interruption.
Active Comparator: 2
Active rTMS to left/right Wernicke's region plus sham rTMS to opposite hemisphere middle temporal cortex
Device: Magstim Rapid-2 system triggering Magstim Super Rapid system
Week 1 includes repetitive rTMS for 5 sessions to either to left or right Wernicke's area (BA22) synchronous with sham rTMS to opposite hemisphere middle temporal cortex (BA21). Week 2 includes rTMS given for 5 sessions with positions reversed (e.g., if Wernicke's stimulation was on the left during Week 1, position of rTMS will switch to the right side during Week 2 and vice-versa). As in Week 1, sham rTMS will also be given synchronously to the opposite hemisphere middle temporal cortex. Weeks 3 and 4 include 10 stimulation sessions to the configuration of sites producing greater improvement in comparing results of Week 1 and Week 2. rTMS for each stimulation session will be given at 1-Hertz (once per second) for 16 minutes without interruption.
Experimental: Non-randomized bilateral rTMS
Active bilateral rTMS to left/right Wernicke's area and opposite side middle temporal gyrus
Device: Magstim Rapid 2 system triggering Magstim Super Rapid system
Week 1 treatment includes rTMS for 5 sessions to either to left or right Wernicke's area (BA22) synchronous with rTMS to opposite hemisphere middle temporal cortex (BA21). Week 2 treatment includes rTMS given for 5 sessions with positions reversed (e.g., if Wernicke's stimulation was on the left during Week 1, position of rTMS will switch to the right side during Week 2 and vice-versa). As in Week 1, active rTMS will also be given synchronously to the opposite hemisphere middle temporal cortex. Weeks 3 and 4 include 10 stimulation sessions to the configuration of sites producing greater improvement in comparing results of Week 1 and Week 2. rTMS for each stimulation session will be given at 1-Hertz (once per second) for 16 minutes without interruption.

Detailed Description:

This study is an extension of an ongoing clinical trial (ClinicalTrials.gov identifier NCT 00308997) that was initiated in 2006. The primary objective of the ongoing clinical trial (hereafter called the "parent trial") is to determine efficacy of rTMS in curbing auditory hallucinations when delivered to a part of the left temporal lobe called Wernicke's area and a corresponding region in the right temporal lobe. The parent trial appears to show robust effects for active rTMS compared to effects of sham stimulation. However, observed responses following active rTMS have often been incomplete. Moreover, in some cases there has been a subsequent return of symptoms 1 to 6 months after the trial ended.

We consequently have initiated a re-enrollment trial where patients who have participated in the parent trial and demonstrated an incomplete response or a subsequent return of symptoms may return to receive additional active rTMS. We hypothesize that efficacy of suppressive rTMS will be enhanced if directed simultaneously to right/left Wernicke's area (the site used in the parent trial) as well as to a second site located in the opposite middle temporal cortex. Roughly half of subjects in the re-enrollment will be randomized to receive active rTMS to right/left Wernicke's area plus active rTMS to opposite hemisphere middle temporal region, while half of subjects will be randomized to receive active rTMS to right/left Wernicke's area plus sham rTMS to opposite hemisphere middle temporal region. The position of the middle temporal regions will be determined by two recently completed brain imaging studies of auditory hallucinations suggesting that activation in these sites triggers auditory hallucinations. The two-position design will allow us to determine if active rTMS delivered to the middle temporal cortex is superior in amplifying efficacy of active rTMS targeting Wernicke's area and in reducing auditory hallucinations to sham stimulation to the same site. The re-enrollment protocol will utilize two rTMS devices simultaneously where one directly triggers the other.

We have added a third arm to the protocol (3/2012) where the same intervention described for Arm 1 is provided to enrollees, but no randomization or comparison with Arm 2 is pursued. The primary purpose of this Arm is to conduct fMRI neuroimaging studies prior to and subsequent to the rTMS intervention. Our intent is to ascertain changes in regional brain activation and connectivity that most robustly predict level of improvement in auditory hallucinations elicited by bilateral rTMS as assessed by our primary outcome variables. This combined fMRI/rTMS study will provide critical new insights into the neurobiological basis of auditory hallucinations.

  Eligibility

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

Inclusion Criteria:

  • Previously enrolled in our "parent" rTMS trial with passage of at least six months since last received active rTMS

Exclusion Criteria:

  • Active substance abuse or alcohol abuse
  • Pregnancy
  • Dose or type of psychiatric medication changed within the 4 weeks prior to study entry
  • Recent head trauma, seizures, or significant unstable medical condition
  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: NCT00567281

Contacts
Contact: Petra Kleinlein, PhD 203-785-7918
Contact: Ralph Hoffman, MD 203-688-9734 ralph.hoffman@yale.edu

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

Additional Information:
Publications:
Hoffman, R.E., Hampson, M., Wu, K., Anderson, A. Gore, J., Buchanan, R.J., Constable, T., Hawkins, K., Sahay, N., Krystal, J.H. Probing the pathophysiology of auditory hallucinations by combining functional magnetic resonance imaging and transcranial magnetic stimulation. Cerebral Cortex 17:2733-2743, 2007.
Hoffman, R.E., Anderson, A., Varanko, M., Gore, J., Hampson, M. The time course of regional brain activation associated with onset of auditory/verbal hallucinations. British Journal of Psychiatry, in press.

Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT00567281     History of Changes
Other Study ID Numbers: R01 MH073673-02, R01MH073673-02, NARSAD, 2R01MH067073
Study First Received: December 3, 2007
Last Updated: June 26, 2014
Health Authority: United States: Federal Government

Keywords provided by Yale University:
Schizoaffective disorder
Auditory Hallucinations
Voices
Repetitive Transcranial Magnetic Stimulation
rTMS
Wernicke's Area
Middle Temporal Cortex
Persistent Auditory Hallucinations
Previously Participated in "Parent" rTMS Protocol

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

ClinicalTrials.gov processed this record on November 20, 2014