Effect of Repetitive Transcranial Magnetic Stimulation on Resting State Brain Activity in Schizophrenia

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
University of Arkansas
ClinicalTrials.gov Identifier:
NCT01620086
First received: June 4, 2012
Last updated: June 20, 2013
Last verified: June 2013
  Purpose

This study compares the efficacy of low and high frequency repetitive transcranial magnetic stimulation (rTMS) as a means of treating subjects with schizophrenia. Magnetic pulses delivered over the scalp cause brain activity. This activity has been shown to help decrease the intensity and frequency of auditory hallucinations (AH) in schizophrenia. The investigators will compare whether low or high frequencies work best. The investigators will also examine what changes occur in the brain that are related to improvement.


Condition Intervention
Schizophrenia
Device: Repetitive Transcranial Magnetic Stimulation (Magstim Rapid2)
Other: Functional magnetic resonance imaging

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Effect of Repetitive Transcranial Magnetic Stimulation (RTMS) on Resting State Brain Activity in Schizophrenia

Resource links provided by NLM:


Further study details as provided by University of Arkansas:

Primary Outcome Measures:
  • Variation of Resting State Brain Activity as Measured by functional Magnetic Resonance Imaging (fMRI) [ Time Frame: 5 months ] [ Designated as safety issue: No ]
    Primary outcome measures of the fMRI data is the functional connectivity between brain regions composing the auditory network. fMRI is an MRI procedure that measures brain activity by detecting associated changes in blood flow The correlation between these regions' functional time courses are expected to vary with disease state and TMS treatment condition. fMRIs taken at baseline and at the end of the study (5 months) will be compared.


Secondary Outcome Measures:
  • Overall Change in the Evoked Response Potential at 50 ms (P50 ERP) Recordings. [ Time Frame: 5 months ] [ Designated as safety issue: No ]
    An evoked response potential, such as a P50 ERP, is an electrical potential recorded from the nervous system following presentation of a stimulus. Subjects listen to auditory tones (i.e., clicks) and count the number of tones until 64 valid ERP recordings are obtained. The ERP recordings taken at Baseline will be compared to those taken at the end of the study (approximately 5 months).

  • Depression Level Changes as Measured by the Hamilton Depression Inventory (HAMD) [ Time Frame: 5 months ] [ Designated as safety issue: No ]
    HAM-D is a multiple choice questionnaire that clinicians administer to rate the severity of a subject's depression. There are 17 questions; each question has between 3-5 possible responses which increase in severity. The clinician chooses the correct response by interviewing the subject and by observing the symptoms. A score of 0-7 is considered to be normal, scores of 20 or higher indicate moderately severe depression. The HAMD results from Baseline evaluation will be compared to results at the end of the study (approximately 5 months).

  • Changes in Auditory Hallucinations Questionnaire (AHQ) [ Time Frame: 5 months ] [ Designated as safety issue: No ]
    The Auditory Hallucinations Questionnaire (AHQ) will be used to determine the subject's perceptions of changes(s). The average results of this test at baseline and at the end of the treatment (approximatly 5 months) will be measured.


Estimated Enrollment: 30
Study Start Date: June 2012
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1- or 10-Hz rTMS
all receive both tx
Device: Repetitive Transcranial Magnetic Stimulation (Magstim Rapid2)

Visits 3-14: 12 sessions in random order 4 days of one type of active rTMS, 4 days of a second type, 4 days of either. After completing 1 type of tx, return in approx 3 wks to complete the next type until all 3 are finished. Subjects fill out questionnaires 3 times during the 3-week period.

Electrodes are placed on muscles of thumb on side of body opposite stimulating coil. There will be muscles twitching and brief movements of the coil and a clicking sound during stimulation. Subjects rate and document auditory hallucinations each day. Image of brain activity (fMRI) will be performed on the last day of each week of tx.

The f/up is 2 months after last session. Subjects complete same questionnaires and rating scales as before. The fMRI will also be performed.

Other Names:
  • Magstim Rapid2
  • P/N 3576-23-08
Controls
These subjects are normals without schizophrenia. They only receive fMRIs.
Other: Functional magnetic resonance imaging
Normal subjects do not have schizophrenia and receive fMRIs on Days 6, 29, 54
Other Names:
  • fMRI
  • normal controls

Detailed Description:

Background. The sub-Investigator Dr. Mennemeier has been using repetitive transcranial magnetic stimulation (rTMS) to treat phantom sound perception in subjects with tinnitus. The Principal Investigator (PI), Dr. Messias, now aims to team up with Drs. Mennemeier and James, to learn how rTMS influences phantom sound perception in schizophrenia. rTMS has already been shown to be an effective treatment for both tinnitus and schizophrenia. rTMS is a non-invasive method of regional brain stimulation that can significantly reduce phantom sound perception temporarily in 50% of subjects with tinnitus and schizophrenia. This study will go further than previous investigations by analyzing how different frequencies of rTMS influence not only auditory hallucinations (AH) in schizophrenia but also brain connectivity in schizophrenia. The investigators want to learn if rTMS decreases AH by normalizing brain connectivity. Whereas this study focuses on schizophrenic subjects with AH, the design is very similar to ongoing work on tinnitus so the findings will be comparable.

Tinnitus and AH in schizophrenia are prevalent and disabling disorders of sound perception. The investigators understanding of the precise mechanisms of these disorders is lacking. Interestingly, the symptoms of both disorders respond positively to rTMS of the temporal cortex in ways that defy contemporary understanding of the nature of these symptoms and of how rTMS should work to improve them. For example, phantom sound perception in both tinnitus and schizophrenia are linked to maladaptive, hyperactivity of auditory processing regions of temporal cortex; however, it is increasingly clear that these pathological changes alone are insufficient to explain the pronounced intrusiveness and negative emotional valance of symptoms in each disorder. Therefore, a barrier to understanding these disorders lies in understanding how changes in auditory cortex are synchronized with changes in other cortical regions that regulate perception and emotion. Additionally, at present, the decision of which rTMS frequency to apply as a treatment for phantom sound perception has no firm theoretical or empirical basis. Whereas, low frequency rTMS has traditionally been used, based upon contemporary models, to "inhibit" hyperactivity in auditory cortex; high frequency rTMS, which should induce an opposite effect on neuronal processing, not only works to improve symptoms but may be more effective for some subjects than low frequency rTMS. Therefore, contemporary models designed to explain how the frequency of rTMS influences neuronal activity immediate following stimulation are insufficient to explain how low and high frequencies of rTMS can mitigate phantom sound perception for days, weeks and months following a single course of treatment.

Hypothesis. The investigators propose that phantom sound perception in schizophrenia result from an imbalance of excitatory and inhibitory neural process in auditory networks and from synchronized, maladaptive changes in linked brain regions that regulate perception and emotion. Treating auditory cortex with repetitive, external magnetic stimulation can decrease phantom sound perception and distress by reversing the maladaptive brain reorganization that is set in motion by these underlying neural imbalances.

  Eligibility

Ages Eligible for Study:   21 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Inclusion Criteria for schizophrenic subjects.

    • Male and female patients, 21-65 years of age, of all races and ethnicities
    • Diagnosis of auditory hallucinations (AH) associated with schizophrenia (verified at screening)
    • Must report experiencing the presence of their phantom auditory perception for at least 6 months
    • Female Subjects of childbearing age must take a pregnancy test to rule out pregnancy prior to participating in this study and during the study.
    • Willing to provide informed consent to participate in all study interventions and assessments
    • Subjects must have the capacity to sign and informed consent or a legal authorized representative (LAR) must sign in addition to the subject.
  • Inclusion Criteria for control subjects.

    • Male and female patients, 21-65 years of age, of all races and ethnicities
    • Willing to provide informed consent to participate in all study interventions and assessments

Exclusion Criteria:

  • Exclusion Criteria for schizophrenic subjects:

    • Subjects with significant neurological disease, acoustic neuromas or glomus tumors, or other contraindicated neuropathology.
    • Claustrophobia, or the inability to lie still in a confined space
    • Additional exclusion criteria for repetitive Transcranial Magnetic Stimulation (rTMS) include the following:

      • a personal or family history of epilepsy;
      • a personal history of head injury, aneurysm, stroke, previous cranial neurosurgery, neurological or psychiatric disorders other than schizophrenia, or migraines
      • recent use of cocaine or alcohol
      • metal implants in the head or neck
      • a pacemaker
      • pregnancy (or the possibility of pregnancy)
      • medications that lower seizure threshold (tricyclic antidepressants or bupropion) or reduce cortical excitation (anticonvulsants or benzodiazepines).
    • Persons under 21 years of age (children) are excluded because the effect of rTMS on children is unknown, in contrast to adults, who have been well studied.
    • Exclusion items specific to Functional Magnetic Resonance Imaging (fMRI):

      • magnetic metallic implants
      • electronic or magnetic implants, such as pacemakers, as these may stop working
      • nonremovable dental implants
      • permanent makeup or tattoos with metallic dyes
      • a positive pregnancy test (for females)
      • a self-reported history of loss of consciousness greater than 10 minutes
      • physical disabilities that prohibit task performance
    • Any other condition that the investigator believes might put the participant at risk
  • Exclusion Criteria for control subjects:

    • Subjects with significant neurological disease, acoustic neuromas or glomus tumors, or other contraindicated neuropathology.
    • Claustrophobia, or the inability to lie still in a confined space
    • Magnetic metallic implants
    • Electronic or magnetic implants, such as pacemakers, as these may stop working
    • Nonremovable dental implants
    • Permanent makeup or tattoos with metallic dyes
    • A positive pregnancy test (for females)
    • A self-reported history of loss of consciousness greater than 10 minutes
    • Physical disabilities that prohibit task performance
    • Any other condition that the investigator believes might put the participant at risk
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01620086

Locations
United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
Sponsors and Collaborators
University of Arkansas
Investigators
Principal Investigator: Erick Messias, MD, MPH, PhD University of Arkansas
  More Information

Additional Information:
No publications provided

Responsible Party: University of Arkansas
ClinicalTrials.gov Identifier: NCT01620086     History of Changes
Other Study ID Numbers: 134662
Study First Received: June 4, 2012
Last Updated: June 20, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Arkansas:
Schizophrenia
Auditory hallucinations (AH)
Phantom sound perception
repetitive transcranial magnetic stimulation (rTMS)
functional magnetic resonance imaging (fMRI)

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders

ClinicalTrials.gov processed this record on April 17, 2014