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

NCT ID: NCT01620086

Last Updated: 2016-10-31

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

26 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-06-30

Study Completion Date

2015-08-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Schizophrenia

Keywords

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Schizophrenia Auditory hallucinations (AH) Phantom sound perception repetitive transcranial magnetic stimulation (rTMS) Percent habituation in the P50 amplitude with 250 ms ISI

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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Patients

Patients with Schizophrenia who meet entry criteria for the study and first receive active repetitive transcranial magnetic stimulation for four days over a control site located at the vertex and then are randomized to receive repetitive Transcranial Magnetic Stimulation for four days over the temporal cortex at both 1 Hz and 10 Hz.

Group Type EXPERIMENTAL

Active Repetitive Transcranial Magnetic Stimulation 1 Hz

Intervention Type DEVICE

active rTMS delivered at 1Hz frequency over temporal cortex

Active Repetitive Transcranial Magnetic Stimulation 10 Hz

Intervention Type DEVICE

active rTMS delivered at 10 Hz frequency over temporal cortex

Active control site Repetitive Transcranial Magnetic Stimulation at 1Hz

Intervention Type DEVICE

active rTMS delivered at either 1 Hz frequency over the vertex

Active control site Repetitive Transcranial Magnetic Stimulation at 10 Hz

Intervention Type DEVICE

Active 10 Hz rTMS delivered over the vertex

Controls

These subjects are normal controls without schizophrenia who receive sham, repetitive transcranial magnetic stimulation at 1 Hz for two days and then receive active, repetitive Transcranial Magnetic stimulation for two days. All stimulation is delivered at the control site located over the vertex.

Group Type EXPERIMENTAL

Active control site Repetitive Transcranial Magnetic Stimulation at 1Hz

Intervention Type DEVICE

active rTMS delivered at either 1 Hz frequency over the vertex

Sham control site Repetitive Transcranial Magnetic Stimulation

Intervention Type DEVICE

sham rTMS delivered at 1Hz frequency over the vertex

Interventions

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Active Repetitive Transcranial Magnetic Stimulation 1 Hz

active rTMS delivered at 1Hz frequency over temporal cortex

Intervention Type DEVICE

Active Repetitive Transcranial Magnetic Stimulation 10 Hz

active rTMS delivered at 10 Hz frequency over temporal cortex

Intervention Type DEVICE

Active control site Repetitive Transcranial Magnetic Stimulation at 1Hz

active rTMS delivered at either 1 Hz frequency over the vertex

Intervention Type DEVICE

Sham control site Repetitive Transcranial Magnetic Stimulation

sham rTMS delivered at 1Hz frequency over the vertex

Intervention Type DEVICE

Active control site Repetitive Transcranial Magnetic Stimulation at 10 Hz

Active 10 Hz rTMS delivered over the vertex

Intervention Type DEVICE

Other Intervention Names

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rTMS rTMS

Eligibility Criteria

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Inclusion Criteria

* 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.

* 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

* 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

* 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

* 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
Minimum Eligible Age

21 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Arkansas

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Erick Messias, MD, MPH, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Arkansas

Locations

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University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Countries

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United States

Other Identifiers

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134662

Identifier Type: -

Identifier Source: org_study_id