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Novel Brain Stimulation Therapies in Stroke Guided Expressions of Plasticity

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ClinicalTrials.gov Identifier: NCT03020433
Recruitment Status : Recruiting
First Posted : January 13, 2017
Last Update Posted : January 13, 2017
Sponsor:
Information provided by (Responsible Party):
Ela B Plow, PhD, PT, The Cleveland Clinic

Brief Summary:
The investigators ultimate goal is to personalize brain stimulation for stroke so outcomes of the upper limb can be maximized for each individual patient. Several groups including the investigators have recently theorized that personalizing stimulation so as to selectively stimulate iM1 in mild, and cPMd in patients with greater severity would help generalize benefits of stimulation. The investigator premise that variances in expressions of plasticity can explain how to best stratify patients for robust, personalized stimulation.

Condition or disease Intervention/treatment Phase
Stroke Cerebrovascular Disorders Nervous System Diseases Brain Diseases Cardiovascular Diseases Vascular Diseases Central Nervous System Diseases Device: rTMS Contralesional M1 Device: rTMS Contralesional PMC Device: rTMS Ipsilesional PMC Device: rTMS sham at Ipsilesional M1 Early Phase 1

Detailed Description:

AIMS: The ultimate goal is to personalize brain stimulation for stroke so outcomes of the upper limb can be maximized for each individual patient. Even though stimulation is one of the most well studied methods to augment plasticity and boost recovery, it is still not approved for outpatient therapy. Benefits of stimulation are weak and variable especially in patients who suffer from greater damage and disability. The key limitation of the standard approach is its generic assumptions about plasticity. The current standard assumes that ipsilesional primary motor cortex (iM1) can impact recovery for patients in all ranges of severity, and intact, contralesional cortices always compete with iM1 to inhibit recovery. But, these long-standing assumptions fail to consider that iM1 or its pathways are damaged in a majority (58-83%) of patients. As such, the potential of iM1 would be weak and variable, and patients will have little option but to rely on plasticity of intact, contralesional cortices that are more likely to survive. Of all surviving cortices, contralesional dorsal premotor cortex (cPMd) expresses plasticity most consistently. cPMd is activated in movement of the paretic limb when activating iM1 is less likely. cPMd even reduces its competition with iM1 and offers its ipsilateral pathways instead to support recovery of the proximal paretic limb when pathways from iM1 are largely damaged.

Several groups including the investigator have recently theorized that personalizing stimulation so as to selectively stimulate iM1 in mild, and cPMd in patients with greater severity would help generalize benefits of stimulation. These theoretical claims, however, remain untested since several gaps exist. For instance, what is the cut-off level of severity that stratifies those who respond to stimulation of iM1 from those who respond to stimulation of cPMd? Even then, are substrates for 'personalized' stimulation same as the substrates that express plasticity in recovery, i.e. if patients benefit from stimulation of cPMd, do they express contralesional plasticity in recovery? Here, the investigator premise that variances in expressions of plasticity can explain how to best stratify patients for robust, personalized stimulation.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Supportive Care
Official Title: Novel Brain Stimulation Therapies in Stroke Guided Expressions of Plasticity
Study Start Date : March 2016
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : December 2017

Arm Intervention/treatment
Active Comparator: rTMS Contralesional M1 Inhibition Device: rTMS Contralesional M1
1Hz Contalesional M1 repetitive transcranial magnetic stimulation (1500 pulses, 25 minutes, 90% AMT
Active Comparator: rTMS Contralesional PMC facilitation Device: rTMS Contralesional PMC
5Hz Contralesional PMC repetitive transcranial magnetic stimulation (1500 pulses, 10 minutes, 5 trains of 300 pulses each with 1 minute rest in between, 90% AMT)
Active Comparator: rTMS Ipsilesional PMC facilitation Device: rTMS Ipsilesional PMC
5HZ Ipsilesional PMC repetitive transcranial magnetic stimulation (1500 pulses, 10 minutes, 5 trains of 300 pulses each with 1 minute rest in between, 90% AMT)
Sham Comparator: rTMS Sham at Ipsilesional M1 Device: rTMS sham at Ipsilesional M1
1Hz Ipsilesional M1 sham repetitive transcranial magnetic stimulation (1500 pulses, 25 minutes, 50% MSO)



Primary Outcome Measures :
  1. Aim 1: Change in time (seconds) to perform functional reaching [ Time Frame: Change in functional reaching from baseline to post rTMS, assessed for approximately 4-6 hours. ]
    Patients will be seated with test arm resting on a table. Three buttons (labeled 1, 2, 3) will be arranged in a semi-circle at 80% of reaching distance of the paretic limb. A number (1, 2, or 3) will cue patients to reach and push the designated button as fast as possible using shoulder flexion-abduction and elbow extension while their trunk is stabilized. Three blocks of 20 trials will be tested pre- and post-rTMS.


Secondary Outcome Measures :
  1. Aim 2:Change in plasticity evoked with rTMS. [ Time Frame: Change in neurophysiology from baseline to post rTMS assessed for approximately 4-6 hours. ]
    Expressions of plasticity will be noted for ipsilesional vs. contralesional pathways and inhibition imposed on ipsilesional cortices from contralesional cortices. Subjects will be stratified based on which stimulation location evoked the most plasticity from each of the arms.



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Ages Eligible for Study:   21 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • greater than 21 years old
  • more than 6 months from first, unilateral index stroke
  • unilateral paresis of the upper limb indexed as greater than or equal to 20% slowness in functional reaching compared to non-paretic limb
  • UEFM less than or equal to 61 out of 66.

Exclusion Criteria:

  • subjects who cannot perform reaching with shoulder
  • severe cognitive deficit (less than or equal to 24 on Mini-Mental State examination.
  • contraindication to TMS or MRI including: seizures, ongoing use of certain neuro- or psycho-active medications, implants, or pacemaker.
  • currently receiving outpatient therapy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03020433


Contacts
Contact: Ela Plow, PhD, PT 216-4454589 plowe2@ccf.org
Contact: Kyle O'Laughlin, MS 216-475-6728 olaughk@ccf.org

Locations
United States, Ohio
Cleveland Clinic Foundation Recruiting
Cleveland, Ohio, United States, 44195
Contact: Ela Plow, PhD, PT    216-445-4589    plowe2@ccf.org   
Contact: Kyle O'Laughlin, MS    216-445-6728    olaughk@ccf.org   
Sponsors and Collaborators
The Cleveland Clinic
Investigators
Principal Investigator: Ela Plow, PhD The Cleveland Clinic

Responsible Party: Ela B Plow, PhD, PT, Associate Staff, The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT03020433     History of Changes
Other Study ID Numbers: 16-128
16GRNT27720019 ( Other Grant/Funding Number: AHA )
First Posted: January 13, 2017    Key Record Dates
Last Update Posted: January 13, 2017
Last Verified: January 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Ela B Plow, PhD, PT, The Cleveland Clinic:
brain diseases
Stroke
rehab
rehabilitation
paresis
paralysis
stroke therapy
CVA
cerebrovascular accident
TMS
transcranial magnetic stimulation
CIMT
constraint induced movement therapy
MRI

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