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Re-Enrollment Repetitive Transcranial Magnetic Stimulation Trial for Auditory Hallucinations

This study is enrolling participants by invitation only.

Sponsored by: National Institute of Mental Health (NIMH)
Information provided by: National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier: NCT00567281
  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 II

MedlinePlus related topics:   Schizophrenia   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment, Randomized, Double Blind (Subject, Caregiver, Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study
Official Title:   Re-Enrollment Bilateral rTMS Clinical Trial for Persistent Auditory Hallucinations

Further study details as provided by National Institute of Mental Health (NIMH):

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:   April 2012
Estimated Primary Completion Date:   April 2012 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
1: Experimental
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.
2: Active Comparator
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.

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.

  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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00567281

Locations
United States, Connecticut
Department of Psychiatry, Yale School of Medicine    
      New Haven, Connecticut, United States, 06519

Sponsors and Collaborators

Investigators
Principal Investigator:     Ralph Hoffman, MD     Yale University    
  More Information

Click here for a description of rTMS trials of auditory hallucinations at Yale  This link exits the ClinicalTrials.gov site
 

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.
 
Hoffman RE, Boutros NN, Hu S, Berman RM, Krystal JH, Charney DS. Transcranial magnetic stimulation and auditory hallucinations in schizophrenia. Lancet. 2000 Mar 25;355(9209):1073-5.
 
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.

Responsible Party:   Yale University School of Medicine ( Ralph Hoffman MD )
Study ID Numbers:   R01 MH73673-substudy1, R01 MH73673, NARSAD
First Received:   December 3, 2007
Last Updated:   March 4, 2008
ClinicalTrials.gov Identifier:   NCT00567281
Health Authority:   United States: Federal Government

Keywords provided by National Institute of Mental Health (NIMH):
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

Study placed in the following topic categories:
Schizophrenia
Signs and Symptoms
Mental Disorders
Hallucinations
Neurologic Manifestations
Psychotic Disorders
Neurobehavioral Manifestations
Schizophrenia and Disorders with Psychotic Features
Perceptual Disorders

Additional relevant MeSH terms:
Nervous System Diseases

ClinicalTrials.gov processed this record on September 08, 2008




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