SchizophreniaNCT01620086
Effect of Repetitive Transcranial Magnetic Stimulation on Resting State Brain Activity in Schizophrenia
A study testing Active Repetitive Transcranial Magnetic Stimulation 1 Hz and Active Repetitive Transcranial Magnetic Stimulation 10 Hz in people with Schizophrenia, run by University of Arkansas at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 21 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Active Repetitive Transcranial Magnetic Stimulation 1 Hz and Active Repetitive Transcranial Magnetic Stimulation 10 Hz
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2012to Aug 2015
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 30Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
About this study
Official title: Effect of Repetitive Transcranial Magnetic Stimulation (RTMS) on Resting State Brain Activity in Schizophrenia
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.
Read the 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.
- Conditions
- Schizophrenia
- Being tested
- Active Repetitive Transcranial Magnetic Stimulation 1 Hz, Active Repetitive Transcranial Magnetic Stimulation 10 Hz, Active control site Repetitive Transcranial Magnetic Stimulation at 1Hz, Sham control site Repetitive Transcranial Magnetic Stimulation, Active control site Repetitive Transcranial Magnetic Stimulation at 10 Hz
- Keywords
- Schizophrenia, Auditory hallucinations (AH), Phantom sound perception, repetitive transcranial magnetic stimulation (rTMS), Percent habituation in the P50 amplitude with 250 ms ISI
- Medical subject headings
- Schizophrenia, Hallucinations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active Repetitive Transcranial Magnetic Stimulation 1 HzDevice
Also called rTMS
active rTMS delivered at 1Hz frequency over temporal cortex
Active Repetitive Transcranial Magnetic Stimulation 10 HzDevice
Also called rTMS
active rTMS delivered at 10 Hz frequency over temporal cortex
Active control site Repetitive Transcranial Magnetic Stimulation at 1HzDevice
active rTMS delivered at either 1 Hz frequency over the vertex
Sham control site Repetitive Transcranial Magnetic StimulationDevice
sham rTMS delivered at 1Hz frequency over the vertex
Active control site Repetitive Transcranial Magnetic Stimulation at 10 HzDevice
Active 10 Hz rTMS delivered over the vertex
| Study group | Role | What they receive |
|---|---|---|
| Patients | Experimental | 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. Receives: Device: Active Repetitive Transcranial Magnetic Stimulation 1 Hz; Device: Active Repetitive Transcranial Magnetic Stimulation 10 Hz; Device: Active control site Repetitive Transcranial Magnetic Stimulation at 1Hz; Device: Active control site Repetitive Transcranial Magnetic Stimulation at 10 Hz |
| Controls | Experimental | 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. Receives: Device: Active control site Repetitive Transcranial Magnetic Stimulation at 1Hz; Device: Sham control site Repetitive Transcranial Magnetic Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Auditory Hallucinations Questionnaire (AHQ).
The Auditory Hallucinations Questionnaire (AHQ) will be used to determine the patient's perceptions of change in auditory hallucinations(s). Normal controls do not fill out this measure because they do not have auditory hallucinations. Change in the average results of this test between the baseline and active treatment weeks (1 and 10 Hz) will be measured. The range of scores is 0-70, higher scores mean more symptoms.
Measured: change between the baseline time point and 4 days of active treatment (patients) or 2 days of sham or active treatment (controls)"
Secondary outcomes (2)
Overall Change in the Percent Habituation of the P50 Evoked Response Potential at 250 Inter Stimulus Interval (ISI) Between the Control and Active Treatments (1 and 10 Hz).
Percent habituation refers to change in the amplitude of the P50 evoked response potential following a 250 ms inter stimulus interval. Change in the average results of this test between the baseline and active treatment weeks (1 and 10 Hz) will be measured.
Measured: change between the baseline time point and 4 days of active treatment (patients) or 2 days of sham or active treatment (controls)"
Depression Level Changes as Measured by the Hamilton Depression Inventory (HAMD).
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 (range 0 to 52). 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. Change in the average results of this test between the baseline and active treatment weeks (1 and 10 Hz) will be measured.
Measured: change between the baseline time point and 4 days of active treatment (patients) or 2 days of sham or active treatment (controls)"
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2012 (estimated)
- Study startJun 2012
- Primary completionAug 2015
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by University of ArkansasThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arkansas
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Erick Messias, MD, MPH, PhD, Principal investigator, University of Arkansas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01620086
- Sponsor's protocol ID
- 134662
- Status last verified
- Oct 2016
- First submitted
- 4 Jun 2012
- Last updated
- 31 Oct 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Repetitive Transcranial Magnetic Stimulation (RTMS) on Resting State Brain Activity in Schizophrenia
- ClinicalTrials.gov ID
- NCT01620086
- Acronym / sponsor ID
- 134662
- Conditions
- Schizophrenia
- Keywords
- Schizophrenia, Auditory hallucinations (AH), Phantom sound perception, repetitive transcranial magnetic stimulation (rTMS), Percent habituation in the P50 amplitude with 250 ms ISI
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- University of ArkansasUniversity, hospital or other
- Study start
- Jun 2012
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 15 Jun 2012 (estimated)
- Results
- Posted 26 Oct 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients | Experimental | Device: Active Repetitive Transcranial Magnetic Stimulation 1 Hz, Device: Active Repetitive Transcranial Magnetic Stimulation 10 Hz, Device: Active control site Repetitive Transcranial Magnetic Stimulation at 1Hz, Device: Active control site Repetitive Transcranial Magnetic Stimulation at 10 HzPatients 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. |
| Controls | Experimental | Device: Active control site Repetitive Transcranial Magnetic Stimulation at 1Hz, Device: Sham control site Repetitive Transcranial Magnetic StimulationThese 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. |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
Key exclusion criteria (30 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Active Repetitive Transcranial Magnetic Stimulation 1 HzAlso: rTMSactive rTMS delivered at 1Hz frequency over temporal cortex | Device | Patients |
| Active Repetitive Transcranial Magnetic Stimulation 10 HzAlso: rTMSactive rTMS delivered at 10 Hz frequency over temporal cortex | Device | Patients |
| Active control site Repetitive Transcranial Magnetic Stimulation at 1Hzactive rTMS delivered at either 1 Hz frequency over the vertex | Device | Controls, Patients |
| Sham control site Repetitive Transcranial Magnetic Stimulationsham rTMS delivered at 1Hz frequency over the vertex | Device | Controls |
| Active control site Repetitive Transcranial Magnetic Stimulation at 10 HzActive 10 Hz rTMS delivered over the vertex | Device | Patients |
Primary outcome
Changes in Auditory Hallucinations Questionnaire (AHQ).
Time frame: change between the baseline time point and 4 days of active treatment (patients) or 2 days of sham or active treatment (controls)"
The Auditory Hallucinations Questionnaire (AHQ) will be used to determine the patient's perceptions of change in auditory hallucinations(s). Normal controls do not fill out this measure because they do not have auditory hallucinations. Change in the average results of this test between the baseline and active treatment weeks (1 and 10 Hz) will be measured. The range of scores is 0-70, higher scores mean more symptoms.
2 secondary outcomes
Overall Change in the Percent Habituation of the P50 Evoked Response Potential at 250 Inter Stimulus Interval (ISI) Between the Control and Active Treatments (1 and 10 Hz).
Time frame: change between the baseline time point and 4 days of active treatment (patients) or 2 days of sham or active treatment (controls)"
Depression Level Changes as Measured by the Hamilton Depression Inventory (HAMD).
Time frame: change between the baseline time point and 4 days of active treatment (patients) or 2 days of sham or active treatment (controls)"
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Erick Messias, MD, MPH, PhD principal investigator
University of Arkansas
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active Repetitive Transcranial Magnetic Stimulation 1 Hz and Active Repetitive Transcranial Magnetic Stimulation 10 Hz in people with Schizophrenia, run by University of Arkansas at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Oct 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in Auditory Hallucinations Questionnaire (AHQ). (time frame: change between the baseline time point and 4 days of active treatment (patients) or 2 days of sham or active treatment (controls)"). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2016.