- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01757821
Primed vs. Unprimed rTMS in Chronic Stroke
6-Hz Primed vs. Unprimed Low-Frequency rTMS in Chronic Stroke
Study Overview
Status
Conditions
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:
1. Primed rTMS will result in greater improvements on the Box and Block test.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Minnesota
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Minneapolis, Minnesota, United States, 55455
- University of Minnesota
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 6-Hz Priming
real 6-Hz primed low-frequency rTMS
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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
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Sham Comparator: Sham 6-Hz Priming
Sham 6-Hz Primed low-frequency rTMS
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10 minutes of sham priming stimulation followed by 10 minutes of 1-Hz low-frequency stimulation delivered to the nonstroke primary motor region
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Active Comparator: Real 1-Hz rTMS only
real 1-Hz rTMS only
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20 minutes of low-frequency rTMS delivered to the nonstroke primary motor region
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Cortical Excitability: Paired-Pulse
Time Frame: Change from Baseline to 20 minutes
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Cortical Excitability of the primary motor cortex on the stroke hemisphere will be assessed using paired-pulse transcranial magnetic stimulation.
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Change from Baseline to 20 minutes
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- BrainPrime
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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