StrokeNCT01757821
Primed vs. Unprimed rTMS in Chronic Stroke
A study testing real 6-Hz primed low-frequency rTMS and real 1-Hz rTMS only in people with Stroke, run by University of Minnesota at 1 site in United States.
Trial summary
The goal of stroke rehabilitation is to restore function to the weak side of the body. However, this is often a difficult task to accomplish due to not only to damage from the stroke, but from increased excitability in the non-stroke side of the brain that inhibits the stroke side from functioning optimally. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stroke
- What is being tested?
- real 6-Hz primed low-frequency rTMS and real 1-Hz rTMS only
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2013to Jul 2014
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 years of age or older
- presence of stroke at least six months duration
- demonstrate at least 10 degrees of active extension at the paretic index finger (metacarpophalangeal joint)
- possess resting motor evoked potential on the stroke hemisphere with TMS testing
- Upper Extremity Fugl Meyer score at least 20 out of 66
- Beck Depression Inventory equal to or less than 19 out of 63
- Mini-Mental State Examination score at least 24 out of 30
- age-appropriate receptive language ability
Who cannot join
- history of seizure within the last two years
- indwelling metal or medical devices incompatible with TMS
- anosognosia
- pregnancy
- any co-morbidities impairing upper extremity function (e.g. fracture)
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Official title: 6-Hz Primed vs. Unprimed Low-Frequency rTMS in Chronic Stroke
The goal of stroke rehabilitation is to restore function to the weak side of the body. However, this is often a difficult task to accomplish due to not only to damage from the stroke, but from increased excitability in the non-stroke side of the brain that inhibits the stroke side from functioning optimally. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive form of brain stimulation that can enhance excitability in the stroke side when applied at a low-frequency on the non-stroke side. By "inhibiting the inhibition" (i.e. disinhibition), rTMS promotes adaptive brain reorganization following stroke. Previous research in healthy individuals demonstrates enhanced effects of low-frequency rTMS when it is preceded by high-frequency (excitatory) rTMS stimulation known as priming. Our lab previously demonstrated the safety of 6-Hz priming with low-frequency rTMS in both adults and children with chronic stroke. However, it is currently unknown whether or not the addition of priming stimulation to low-frequency rTMS enhances excitability in the stroke hemisphere. Our study will examine three rTMS interventions in twelve adults (at least 18 years): 1.) 10 minutes of real priming followed by 10 minutes of low-frequency rTMS, 2.) 10 minutes of fake priming followed by 10 minutes of low-frequency rTMS, 3.) 20 minutes of low-frequency rTMS only. Participants will receive all three interventions in randomized order. Each week, participants will complete two pretest and 3 posttest sessions consisting of behavioral measures of weak upper extremity function and cortical excitability in addition to receiving one rTMS intervention. Following each week of testing and treatment, subjects will take a one week rest break before crossing-over to receive another intervention. We hypothesize the following: 1.) Primed rTMS will result in significantly reduced inhibition and significantly increased excitation on the stroke side vs. fake primed rTMS or low-frequency rTMS given alone and 2.) Primed rTMS will result in greater improvements of paretic hand function. This study is innovative in that it intends to compare primed and unprimed rTMS in the stroke brain that could acknowledge a more effective delivery method of rTMS to potentially yield greater rehabilitative outcomes.
Read the detailed description
Recovery following stroke is difficult not only because of the neuronal death from the ischemic insult but also because of maladaptive brain reorganization occurring from exaggerated inhibition imparted by the over-compensating contralesional primary motor area (M1) onto the ipsilesional M1 via transcallosal pathways. Advancement in stroke rehabilitation depends on innovative treatments like repetitive transcranial magnetic stimulation (rTMS) that possess the ability to disrupt this excessive inhibition. Through previous NIH/NICHD funding, my sponsor's research team confirmed the safety and efficacy of rTMS in both adult (1R01 HD053153-01A2) and children (1RC1 HD063838-01) with stroke using 6-Hz primed low-frequency rTMS applied to the contralesional M1 to produce disinhibition of the ipsilesional M1. With feasibility of primed rTMS now demonstrated, the proposed research plan will directly compare primed rTMS to unprimed rTMS. The investigators will investigate whether pretreatment of inhibitory low-frequency rTMS with excitatory high-frequency priming is more effective than sham-primed low-frequency rTMS in correcting the exaggerated interhemispheric inhibition acting on ipsilesional M1. While this may sound contradictory, the Bienenstock-Cooper-Munro theory of bidirectional plasticity supports this concept. The long-term goal is to discover the most effective rTMS protocol with which to safely up-regulate ipsilesional M1, rendering a more potent neuronal network for voluntary recruitment. By studying the efficacy of priming as measured by the amount of cortical excitability in both ipsilesional and contralesional hemispheres, a more advantageous delivery of rTMS may be realized and eventually incorporated into research trials and clinical practice. The study poses significant innovation as it explores the role of metaplasticity in rehabilitation using rTMS. The investigators will employ a double-blind crossover study using twelve adult participants with stroke. Because of heterogeneity in stroke type and location between subjects, a crossover design will reduce variability as each subject serves as their own control.
Specific Aim #1: Compare the effect of 6-Hz primed vs. unprimed low-frequency rTMS on cortical excitability in chronic stroke.Cortical excitability will be explored with TMS using ipsilesional paired-pulse testing, cortical silent period testing, and interhemispheric inhibition (IHI) paired-pulse testing.
Working hypotheses are:
- Primed rTMS will result in greater increases in the 3-ms and 15-ms ipsilesional paired-pulse to single-pulse (ipsilesional PP/SP) ratios than unprimed rTMS, indicating of decreased intracortical inhibition (GABAA-mediated) and greater intracortical facilitation, respectively.
- Primed rTMS will result in greater decreases than unprimed rTMS in duration of cortical silent period, indicating decreased inhibition (GABAB-mediated).
- Primed rTMS will result in a greater increase in the IHI PP/SP ratio in the non-stroke to stroke hemisphere direction and a corresponding decrease in the IHI PP/SP ratio in the stroke to non-stroke hemisphere direction than unprimed rTMS. This is consistent with less inhibition imparted onto the stroke hemisphere from the non-stroke hemisphere and greater inhibition imparted on the non-stroke hemisphere from the stroke hemisphere.
Specific Aim #2: Compare the effect of 6-Hz primed vs. unprimed low-frequency rTMS on functional outcome in chronic stroke. Functional outcome will be assessed by paretic hand performance on the Box and Block test.
Working hypothesis is:
- Primed rTMS will result in greater improvements on the Box and Block test.
- Conditions
- Stroke
- Being tested
- real 6-Hz primed low-frequency rTMS, Sham 6-Hz Primed low-frequency rTMS, real 1-Hz rTMS only
- Keywords
- Stroke, rTMS, TMS
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
real 6-Hz primed low-frequency rTMSDevice
10 minutes of 6-Hz stimulation (real priming) followed by 10 minutes of 1-Hz low-frequency stimulation delivered to the nonstroke primary motor region
Sham 6-Hz Primed low-frequency rTMSDevice
10 minutes of sham priming stimulation followed by 10 minutes of 1-Hz low-frequency stimulation delivered to the nonstroke primary motor region
real 1-Hz rTMS onlyDevice
20 minutes of low-frequency rTMS delivered to the nonstroke primary motor region
| Study group | Role | What they receive |
|---|---|---|
| 6-Hz Priming | Experimental | real 6-Hz primed low-frequency rTMS Receives: Device: real 6-Hz primed low-frequency rTMS |
| Sham 6-Hz Priming | Sham comparator | Sham 6-Hz Primed low-frequency rTMS Receives: Device: Sham 6-Hz Primed low-frequency rTMS |
| Real 1-Hz rTMS only | Active comparator | real 1-Hz rTMS only Receives: Device: real 1-Hz rTMS only |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Cortical Excitability: Paired-Pulse
Cortical Excitability of the primary motor cortex on the stroke hemisphere will be assessed using paired-pulse transcranial magnetic stimulation.
Measured: Change from Baseline to 20 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Dec 2012 (estimated)
- Study startApr 2013
- Primary completionJul 2014
- Study completionJul 2014
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 StrokeStudies of the same condition, open and under way.
- 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- James R Carey, PhD, PT, Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01757821
- Sponsor's protocol ID
- BrainPrime
- Status last verified
- Oct 2017
- First submitted
- 18 Dec 2012
- Last updated
- 2 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 6-Hz Primed vs. Unprimed Low-Frequency rTMS in Chronic Stroke
- ClinicalTrials.gov ID
- NCT01757821
- Acronym / sponsor ID
- BrainPrime
- Conditions
- Stroke
- Keywords
- Stroke, rTMS, TMS
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Study start
- Apr 2013
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 31 Dec 2012 (estimated)
- Results
- Posted 2 Dec 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of stroke rehabilitation is to restore function to the weak side of the body. However, this is often a difficult task to accomplish due to not only to damage from the stroke, but from increased excitability in the non-stroke side of the brain that inhibits the stroke side from functioning optimally. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive form of brain stimulation that can enhance excitability in the stroke side when applied at a low-frequency on the non-stroke side. By "inhibiting the inhibition" (i.e. disinhibition), rTMS promotes adaptive brain reorganization following stroke. Previous research in healthy individuals demonstrates enhanced effects of low-frequency rTMS when it is preceded by high-frequency (excitatory) rTMS stimulation known as priming. Our lab previously demonstrated the safety of 6-Hz priming with low-frequency rTMS in both adults and children with chronic stroke. However, it is currently unknown whether or not the addition of priming stimulation to low-frequency rTMS enhances excitability in the stroke hemisphere. Our study will examine three rTMS interventions in twelve adults (at least 18 years): 1.) 10 minutes of real priming followed by 10 minutes of low-frequency rTMS, 2.) 10 minutes of fake priming followed by 10 minutes of low-frequency rTMS, 3.) 20 minutes of low-frequency rTMS only. Participants will receive all three interventions in randomized order. Each week, participants will complete two pretest and 3 posttest sessions consisting of behavioral measures of weak upper extremity function and cortical excitability in addition to receiving one rTMS intervention. Following each week of testing and treatment, subjects will take a one week rest break before crossing-over to receive another intervention. We hypothesize the following: 1.) Primed rTMS will result in significantly reduced inhibition and significantly increased excitation on the stroke side vs. fake primed rTMS or low-frequency rTMS given alone and 2.) Primed rTMS will result in greater improvements of paretic hand function. This study is innovative in that it intends to compare primed and unprimed rTMS in the stroke brain that could acknowledge a more effective delivery method of rTMS to potentially yield greater rehabilitative outcomes.
Detailed description
Recovery following stroke is difficult not only because of the neuronal death from the ischemic insult but also because of maladaptive brain reorganization occurring from exaggerated inhibition imparted by the over-compensating contralesional primary motor area (M1) onto the ipsilesional M1 via transcallosal pathways. Advancement in stroke rehabilitation depends on innovative treatments like repetitive transcranial magnetic stimulation (rTMS) that possess the ability to disrupt this excessive inhibition. Through previous NIH/NICHD funding, my sponsor's research team confirmed the safety and efficacy of rTMS in both adult (1R01 HD053153-01A2) and children (1RC1 HD063838-01) with stroke using 6-Hz primed low-frequency rTMS applied to the contralesional M1 to produce disinhibition of the ipsilesional M1. With feasibility of primed rTMS now demonstrated, the proposed research plan will directly compare primed rTMS to unprimed rTMS. The investigators will investigate whether pretreatment of inhibitory low-frequency rTMS with excitatory high-frequency priming is more effective than sham-primed low-frequency rTMS in correcting the exaggerated interhemispheric inhibition acting on ipsilesional M1. While this may sound contradictory, the Bienenstock-Cooper-Munro theory of bidirectional plasticity supports this concept. The long-term goal is to discover the most effective rTMS protocol with which to safely up-regulate ipsilesional M1, rendering a more potent neuronal network for voluntary recruitment. By studying the efficacy of priming as measured by the amount of cortical excitability in both ipsilesional and contralesional hemispheres, a more advantageous delivery of rTMS may be realized and eventually incorporated into research trials and clinical practice. The study poses significant innovation as it explores the role of metaplasticity in rehabilitation using rTMS. The investigators will employ a double-blind crossover study using twelve adult participants with stroke. Because of heterogeneity in stroke type and location between subjects, a crossover design will reduce variability as each subject serves as their own control.
Specific Aim #1: Compare the effect of 6-Hz primed vs. unprimed low-frequency rTMS on cortical excitability in chronic stroke.Cortical excitability will be explored with TMS using ipsilesional paired-pulse testing, cortical silent period testing, and interhemispheric inhibition (IHI) paired-pulse testing.
Working hypotheses are:
- Primed rTMS will result in greater increases in the 3-ms and 15-ms ipsilesional paired-pulse to single-pulse (ipsilesional PP/SP) ratios than unprimed rTMS, indicating of decreased intracortical inhibition (GABAA-mediated) and greater intracortical facilitation, respectively.
- Primed rTMS will result in greater decreases than unprimed rTMS in duration of cortical silent period, indicating decreased inhibition (GABAB-mediated).
- Primed rTMS will result in a greater increase in the IHI PP/SP ratio in the non-stroke to stroke hemisphere direction and a corresponding decrease in the IHI PP/SP ratio in the stroke to non-stroke hemisphere direction than unprimed rTMS. This is consistent with less inhibition imparted onto the stroke hemisphere from the non-stroke hemisphere and greater inhibition imparted on the non-stroke hemisphere from the stroke hemisphere.
Specific Aim #2: Compare the effect of 6-Hz primed vs. unprimed low-frequency rTMS on functional outcome in chronic stroke. Functional outcome will be assessed by paretic hand performance on the Box and Block test.
Working hypothesis is:
- Primed rTMS will result in greater improvements on the Box and Block test.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 6-Hz Priming | Experimental | Device: real 6-Hz primed low-frequency rTMSreal 6-Hz primed low-frequency rTMS |
| Sham 6-Hz Priming | Sham comparator | Device: Sham 6-Hz Primed low-frequency rTMSSham 6-Hz Primed low-frequency rTMS |
| Real 1-Hz rTMS only | Active comparator | Device: real 1-Hz rTMS onlyreal 1-Hz rTMS only |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 18 years of age or older
- presence of stroke at least six months duration
- demonstrate at least 10 degrees of active extension at the paretic index finger (metacarpophalangeal joint)
- possess resting motor evoked potential on the stroke hemisphere with TMS testing
- Upper Extremity Fugl Meyer score at least 20 out of 66
Key exclusion criteria (5 listed)
- history of seizure within the last two years
- indwelling metal or medical devices incompatible with TMS
- anosognosia
- pregnancy
- any co-morbidities impairing upper extremity function (e.g. fracture)
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 |
|---|---|---|
| real 6-Hz primed low-frequency rTMS10 minutes of 6-Hz stimulation (real priming) followed by 10 minutes of 1-Hz low-frequency stimulation delivered to the nonstroke primary motor region | Device | 6-Hz Priming |
| Sham 6-Hz Primed low-frequency rTMS10 minutes of sham priming stimulation followed by 10 minutes of 1-Hz low-frequency stimulation delivered to the nonstroke primary motor region | Device | Sham 6-Hz Priming |
| real 1-Hz rTMS only20 minutes of low-frequency rTMS delivered to the nonstroke primary motor region | Device | Real 1-Hz rTMS only |
Primary outcome
Change in Cortical Excitability: Paired-Pulse
Time frame: Change from Baseline to 20 minutes
Cortical Excitability of the primary motor cortex on the stroke hemisphere will be assessed using paired-pulse transcranial magnetic stimulation.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Stroke
RecruitingPhase 1/2
Safety and Efficacy of CG-BM1 in Ischemic Stroke
Ischemic Stroke or High-risk TIA (ABCD² ≥ 4)
Not yet recruitingPhase 3
Recombinant Human Prourokinase for Acute Ischemic Stroke in the Extended Window Selected by CT-Based Artificial Intelligence
Acute Ischemic Stroke
Recruiting
Effects of Mirror Therapy and Motor Imagery on Upper Limb Motor Functions in Middle Cerebral Artery Stroke
Stroke
Recruiting
Rapid Local Ischemic Postconditioning on Stroke After Thrombectomy
Acute Ischemic Stroke
Not yet recruitingObservational study
The GEIR Registry: Rationale and Design of the First Nationwide Multicentre Retinal Stroke Registry in Spain
Retinal Artery Occlusion
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.
James R Carey, PhD, PT principal investigator
University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing real 6-Hz primed low-frequency rTMS and real 1-Hz rTMS only in people with Stroke, run by University of Minnesota 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 5 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 2 Dec 2017. 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. 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?
Yes. Results are posted in the registry (first posted 2 Dec 2017). 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?
Change in Cortical Excitability: Paired-Pulse (time frame: Change from Baseline to 20 minutes). 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 2 Dec 2017.