SchizophreniaNCT01494623
The Effect of Repetitive Transcranial Magnetic Stimulation (rTMS) on Working Memory
A study testing repetitive Transcranial Magnetic Stimulation in people with Schizophrenia, run by Centre for Addiction and Mental Health at 1 site in Canada.
Trial summary
Deficits in working memory (WM) performance are the most significant cognitive impairments in schizophrenia (SCZ). It has also been shown that WM performance is contingent on the cortex synchronization, a process that relies on brain inhibition. Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia
- What is being tested?
- repetitive Transcranial Magnetic Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 122 participants
- Where
- 1 siteCanada
- Study dates
- May 2006to Nov 2012
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 18 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Voluntary and competent to consent
- SCID-IV Diagnosis of Schizophrenia or Schizoaffective Disorder
- Between the ages of 18 and 85
- voluntary and competent to consent
- between the ages of 18-85
- considered a healthy individual free of psychopathology based on the Personality Assessment Inventory
Show all 17Show fewer
- right-handed determined by the TMS screening and demographic form
- self-reported non-smoker
- do not have a self-reported concomitant major medical or neurologic illness
- if a woman of childbearing potential, must be on an effective means of birth control determined through completion of the TMS screening and demographic form.
- Exclusion Criteria for both Healthy Controls and Schizophrenia Subjects:
- Have a DSM-IV history of substance abuse or dependence in the last 6 months
- Have a concomitant major and unstable medical or neurologic illness
- Have a history of seizures
- Have a first degree relative with a history of a seizure disorder
- Are pregnant
- Have any clinically significant EEG activity indicating an increased risk of seizure, as confirmed by a neurologist.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Treating Working Memory Deficits in Patients With Schizophrenia Using Repetitive Transcranial Magnetic Stimulation (rTMS)
Deficits in working memory (WM) performance are the most significant cognitive impairments in schizophrenia (SCZ). It has also been shown that WM performance is contingent on the cortex synchronization, a process that relies on brain inhibition. Repetitive Transcranial Magnetic Stimulation (rTMS) has been demonstrated as an effective treatment for patients with SCZ and has been shown to increase brain inhibition and improve cognitive performance. In this study the investigators intend to:
- evaluate rTMS as a treatment for WM deficits in SCZ
- evaluate rTMS as a method to increase WM performance in healthy individuals
- determine if improvements in WM performance are related to enhanced synchronization of brain networks
- determine whether genetic polymorphisms predict cortical function and treatment response
- evaluate the influence of rTMS treatment on brain structure.
Read the detailed description
To directly investigate whether enhanced gamma synchrony mediates rTMS enhancement of WM in patients with SCZ, and in healthy individuals the investigators propose the following study. The relationship between the improvements in WM performance and increased gamma synchrony following rTMS over the DLPFC will be investigated. Moreover, using statistical models, the investigators will further examine whether increased gamma synchrony mediates WM improvement in these patients. Therefore, in this study the investigators hope to clarify the neurophysiological mechanisms through which rTMS exerts its therapeutic effects on WM performance and develop rTMS as a novel therapeutic tool to enhance the treatment options available for one of the core cognitive deficits in this disorder.
There is considerable evidence to support the fact that WM deficits in schizophrenia are heritable and have a strong genetic component. This evidence emerges from genetic association studies, and studies demonstrating that unaffected relatives of schizophrenia patients also suffer WM deficits. Therefore, treatment response to rTMS may be at least partly contingent on genetic variation within each individual. In particular, GABAergic genes that code for GABAergic proteins which largely determine cortical inhibition may play a key role in treatment response to rTMS over the DLPFC. However, several other gene systems that interact with the GABAergic system may also play a role, and would also merit investigation. Similarly brain structure may also determine treatment response. For instance, volume or thickness of the DLPFC and DLPFC related circuitry has been shown to play a role in WM performance, and therefore, may be a biomarker of treatment response.
Objective 1: To improve WM in patients with SCZ, and in healthy individuals using rTMS.
Hypothesis 1:20 Hz rTMS over the DLPFC will be superior to sham stimulation in improving WM performance in patients with SCZ, and healthy individuals.
Objective 2: To evaluate if high frequency rTMS results in enhanced gamma synchrony SCZ and healthy individuals.
Hypothesis 2: 20 Hz rTMS over the DLPRC will be superior to sham stimulation at increasing gamma synchrony in patients with SCZ, and healthy individuals.
Objective 3: To determine if the rTMS induced increase in gamma band synchrony mediates the therapeutic effects of rTMS on WM performance in patients with SCZ and healthy individuals.
Hypothesis 3: Increased gamma band synchrony will be shown to mediate the therapeutic effects of rTMS on WM performance in SCZ and healthy individuals.
Objective 4: To test whether key polymorphisms in the GABAergic system, and related gene systems determine γ oscillatory activity and WM improvement following rTMS.
Hypothesis 4: GABAergic gene and related gene polymorphisms will determine variation in γ oscillatory activity and WM performance following rTMS treatment.
Objective 5: To examine whether brain structure is a biomarker of treatment response to rTMS Hypothesis 5: Increase in cortical thickness at DLPFC and in microstructural integrity in cortico-cortical white matter tracts connecting to DLPFC will correlate with n-back task performance after rTMS treatment.
- Conditions
- Schizophrenia
- Being tested
- repetitive Transcranial Magnetic Stimulation
- Keywords
- working memory, schizophrenia, cognition, rTMS
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
repetitive Transcranial Magnetic StimulationDevice
Also called MagPro X100 Series (Medtronic A/S, Copenhagen, Denmark)
Magnetic pulses to specified brain regions.
| Study group | Role | What they receive |
|---|---|---|
| Active rTMS | Active comparator | Active treatment will be delivered at an intensity that is 90% of the RMT. Stimulation will be delivered at either 20 Hz or 10 Hz, depending on the patients' tolerance to the stimulation, with 50 stimulation trains of 30 stimuli each (i.e., 1500 stimuli) and an intertrain interval of 30 sec. 25 trains will be applied to to the left or right hemisphere followed by the other hemisphere. Receives: Device: repetitive Transcranial Magnetic Stimulation |
| Sham rTMS | Sham comparator | Sham stimulation will be delivered using the same stimulation parameters and at the site of active treatment, but with only the side-edge resting on the scalp. The coil will be angled 45 degrees away from the skull in a single-wing tilt position. This method produces sound and some somatic sensation (e.g., contraction of scalp muscles) similar to those of active stimulation, but with minimal direct brain effects. Receives: Device: repetitive Transcranial Magnetic Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome measure will be the performance on the N-back working memory task.
Specifically, we will evaluate if rTMS results in changes to the number of correct answers, omissions and errors as well as reaction times.
Measured: 4 weeks
Secondary outcomes (2)
Increase in gamma band synchrony
To ascertain whether high frequency rTMS is superior to sham stimulation in increasing gamma band synchrony our analysis will examine stimulus-locked changes in spectral power, phase, and coherence between electrodes.
Measured: 4 weeks
Brain Imaging Changes
For brain imaging we will test for group differences using: (1) cortical thickness (2) volumetric measures, (3)diffusion based measures. Statistical tests measuring these differences will be conducted at baseline and at the conclusion of the study. We will control for possible effects of neuroleptic medication on MRI measures by regressing mean dosage levels multiplied by number of years on medication, for each of five classes of medication (typical neuroleptics, atypical neuroleptics, antiparkinsonian anticholinergics, lithium, benzodiazepines)
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2011 (estimated)
- Study startMay 2006
- Primary completionNov 2012
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by Centre for Addiction and Mental HealthThe 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
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 122 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Z. J. Daskalakis, Centre for Addiction and Mental Health
- Investigators
- Z. Jeff Daskalakis, MD, PhD, Principal investigator, CAMH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01494623
- Sponsor's protocol ID
- 098 / 2006
- Status last verified
- Jun 2013
- First submitted
- 14 Dec 2011
- Last updated
- 11 Jun 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Barr MS, Farzan F, Rajji TK, Voineskos AN, Blumberger DM, Arenovich T, Fitzgerald PB, Daskalakis ZJ. Can repetitive magnetic stimulation improve cognition in schizophrenia? Pilot data from a randomized controlled trial. Biol Psychiatry. 2013 Mar 15;73(6):510-7. doi: 10.1016/j.biopsych.2012.08.020. Epub 2012 Oct 3.
PubMed 23039931
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treating Working Memory Deficits in Patients With Schizophrenia Using Repetitive Transcranial Magnetic Stimulation (rTMS)
- ClinicalTrials.gov ID
- NCT01494623
- Acronym / sponsor ID
- 098 / 2006
- Conditions
- Schizophrenia
- Keywords
- working memory, schizophrenia, cognition, rTMS
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 122 participants (actual)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Study start
- May 2006
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 19 Dec 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Deficits in working memory (WM) performance are the most significant cognitive impairments in schizophrenia (SCZ). It has also been shown that WM performance is contingent on the cortex synchronization, a process that relies on brain inhibition. Repetitive Transcranial Magnetic Stimulation (rTMS) has been demonstrated as an effective treatment for patients with SCZ and has been shown to increase brain inhibition and improve cognitive performance. In this study the investigators intend to:
- evaluate rTMS as a treatment for WM deficits in SCZ
- evaluate rTMS as a method to increase WM performance in healthy individuals
- determine if improvements in WM performance are related to enhanced synchronization of brain networks
- determine whether genetic polymorphisms predict cortical function and treatment response
- evaluate the influence of rTMS treatment on brain structure.
Detailed description
To directly investigate whether enhanced gamma synchrony mediates rTMS enhancement of WM in patients with SCZ, and in healthy individuals the investigators propose the following study. The relationship between the improvements in WM performance and increased gamma synchrony following rTMS over the DLPFC will be investigated. Moreover, using statistical models, the investigators will further examine whether increased gamma synchrony mediates WM improvement in these patients. Therefore, in this study the investigators hope to clarify the neurophysiological mechanisms through which rTMS exerts its therapeutic effects on WM performance and develop rTMS as a novel therapeutic tool to enhance the treatment options available for one of the core cognitive deficits in this disorder.
There is considerable evidence to support the fact that WM deficits in schizophrenia are heritable and have a strong genetic component. This evidence emerges from genetic association studies, and studies demonstrating that unaffected relatives of schizophrenia patients also suffer WM deficits. Therefore, treatment response to rTMS may be at least partly contingent on genetic variation within each individual. In particular, GABAergic genes that code for GABAergic proteins which largely determine cortical inhibition may play a key role in treatment response to rTMS over the DLPFC. However, several other gene systems that interact with the GABAergic system may also play a role, and would also merit investigation. Similarly brain structure may also determine treatment response. For instance, volume or thickness of the DLPFC and DLPFC related circuitry has been shown to play a role in WM performance, and therefore, may be a biomarker of treatment response.
Objective 1: To improve WM in patients with SCZ, and in healthy individuals using rTMS.
Hypothesis 1:20 Hz rTMS over the DLPFC will be superior to sham stimulation in improving WM performance in patients with SCZ, and healthy individuals.
Objective 2: To evaluate if high frequency rTMS results in enhanced gamma synchrony SCZ and healthy individuals.
Hypothesis 2: 20 Hz rTMS over the DLPRC will be superior to sham stimulation at increasing gamma synchrony in patients with SCZ, and healthy individuals.
Objective 3: To determine if the rTMS induced increase in gamma band synchrony mediates the therapeutic effects of rTMS on WM performance in patients with SCZ and healthy individuals.
Hypothesis 3: Increased gamma band synchrony will be shown to mediate the therapeutic effects of rTMS on WM performance in SCZ and healthy individuals.
Objective 4: To test whether key polymorphisms in the GABAergic system, and related gene systems determine γ oscillatory activity and WM improvement following rTMS.
Hypothesis 4: GABAergic gene and related gene polymorphisms will determine variation in γ oscillatory activity and WM performance following rTMS treatment.
Objective 5: To examine whether brain structure is a biomarker of treatment response to rTMS Hypothesis 5: Increase in cortical thickness at DLPFC and in microstructural integrity in cortico-cortical white matter tracts connecting to DLPFC will correlate with n-back task performance after rTMS treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active rTMS | Active comparator | Device: repetitive Transcranial Magnetic StimulationActive treatment will be delivered at an intensity that is 90% of the RMT. Stimulation will be delivered at either 20 Hz or 10 Hz, depending on the patients' tolerance to the stimulation, with 50 stimulation trains of 30 stimuli each (i.e., 1500 stimuli) and an intertrain interval of 30 sec. 25 trains will be applied to to the left or right hemisphere followed by the other hemisphere. |
| Sham rTMS | Sham comparator | Device: repetitive Transcranial Magnetic StimulationSham stimulation will be delivered using the same stimulation parameters and at the site of active treatment, but with only the side-edge resting on the scalp. The coil will be angled 45 degrees away from the skull in a single-wing tilt position. This method produces sound and some somatic sensation (e.g., contraction of scalp muscles) similar to those of active stimulation, but with minimal direct brain effects. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Voluntary and competent to consent
- SCID-IV Diagnosis of Schizophrenia or Schizoaffective Disorder
- Between the ages of 18 and 85
- voluntary and competent to consent
- between the ages of 18-85
Key exclusion criteria (0 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 |
|---|---|---|
| repetitive Transcranial Magnetic StimulationAlso: MagPro X100 Series (Medtronic A/S, Copenhagen, Denmark)Magnetic pulses to specified brain regions. | Device | Active rTMS, Sham rTMS |
Primary outcome
The primary outcome measure will be the performance on the N-back working memory task.
Time frame: 4 weeks
Specifically, we will evaluate if rTMS results in changes to the number of correct answers, omissions and errors as well as reaction times.
2 secondary outcomes
Increase in gamma band synchrony
Time frame: 4 weeks
Brain Imaging Changes
Time frame: 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2013.
- Derived from this study: PubMed 23039931Barr MS, Farzan F, Rajji TK, Voineskos AN, Blumberger DM, Arenovich T, Fitzgerald PB, Daskalakis ZJ. Can repetitive magnetic stimulation improve cognition in schizophrenia? Pilot data from a randomized controlled trial. Biol Psychiatry. 2013 Mar 15;73(6):510-7. doi: 10.1016/j.biopsych.2012.08.020. Epub 2012 Oct 3.
- Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching hospital, fully affiliated with the University of Toronto, and a PAHO/WHO Collaborating CentreLink provided by the sponsor.
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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.
Z. Jeff Daskalakis, MD, PhD principal investigator
CAMH
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing repetitive Transcranial Magnetic Stimulation in people with Schizophrenia, run by Centre for Addiction and Mental Health at 1 site in Canada.
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 17 inclusion and 0 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 11 Jun 2013. 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 Canada. 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. Some participants in this study may receive a placebo. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The primary outcome measure will be the performance on the N-back working memory task. (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01494623, which also lists 1 linked publication.
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 11 Jun 2013.