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Trial record 19 of 362 for:    rtms

Primed vs. Unprimed rTMS in Chronic Stroke

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:
NCT01757821
First received: December 18, 2012
Last updated: September 3, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Stroke
Device: real 6-Hz primed low-frequency rTMS
Device: Sham 6-Hz Primed low-frequency rTMS
Device: real 1-Hz rTMS only
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: 6-Hz Primed vs. Unprimed Low-Frequency rTMS in Chronic Stroke

Further study details as provided by University of Minnesota - Clinical and Translational Science Institute:

Primary Outcome Measures:
  • Cortical Excitability: Paired-Pulse [ Time Frame: Change from Pretest to Posttest ] [ Designated as safety issue: No ]
    Cortical Excitability of the primary motor cortex on the stroke hemisphere will be assessed using paired-pulse transcranial magnetic stimulation.

  • Cortical Excitability: Interhemispheric Inhibition Testing [ Time Frame: Change from Pretest to Posttest ] [ Designated as safety issue: No ]
    Cortical excitability between the stroke and non-stroke hemispheres will be assessed with inter hemispheric inhibition testing by delivering paired-pulse transcranial magnetic stimulation to the primary motor regions of the stroke and non-stroke hemispheres simultaneously.

  • Cortical Excitability: Cortical Silent Period [ Time Frame: Change from Pretest to Posttest ] [ Designated as safety issue: No ]
    We will measure cortical excitability of the primary motor region on the stroke hemisphere using single-pulse transcranial magnetic stimulation.


Secondary Outcome Measures:
  • Box and Block Test [ Time Frame: Change from Pretest to Posttest ] [ Designated as safety issue: Yes ]
    We will measure paretic hand function using the Box and Block Test. Participants will move as many 2.5cm cube blocks from one compartment to another using their paretic upper extremity over three 60-second trials.


Enrollment: 11
Study Start Date: April 2013
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: real 6-Hz Priming
real 6-Hz primed low-frequency rTMS
Device: real 6-Hz primed low-frequency rTMS
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 Comparator: Sham 6-Hz Priming
Sham 6-Hz Primed low-frequency rTMS
Device: Sham 6-Hz Primed low-frequency rTMS
10 minutes of sham priming stimulation followed by 10 minutes of 1-Hz low-frequency stimulation delivered to the nonstroke primary motor region
Active Comparator: Real 1-Hz rTMS only
real 1-Hz rTMS only
Device: real 1-Hz rTMS only
20 minutes of low-frequency rTMS delivered to the nonstroke primary motor region

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:

  1. 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.
  2. Primed rTMS will result in greater decreases than unprimed rTMS in duration of cortical silent period, indicating decreased inhibition (GABAB-mediated).
  3. 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01757821

Locations
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
Investigators
Principal Investigator: James R Carey, PhD, PT University of Minnesota - Clinical and Translational Science Institute
  More Information

No publications provided

Responsible Party: University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier: NCT01757821     History of Changes
Other Study ID Numbers: BrainPrime
Study First Received: December 18, 2012
Last Updated: September 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Minnesota - Clinical and Translational Science Institute:
Stroke
rTMS
TMS

Additional relevant MeSH terms:
Cerebral Infarction
Stroke
Brain Diseases
Brain Infarction
Brain Ischemia
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Nervous System Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on November 20, 2014