Brain Stimulation-aided Stroke Rehabilitation: Neural Mechanisms of Recovery

Phase 1

Completed

• Conditions: Stroke
• Interventions: Behavioral: Constraint induced movement therapy (CIMT)

• Registration Number: NCT01539096
• Lead Sponsor: The Cleveland Clinic

Brief Summary

The purpose of this study is to investigate whether benefits of training the affected hand in patients with stroke can be improved by combining training with a painless, noninvasive technique called Transcranial Direct Current Stimulation (TDCS). TDCS will be applied over the part of the brain responsible for movements of the affected hand. Also, the investigators will study the changes in the brain that favor recovery of hand function following combination of training and tDCS.

Detailed Description

The overall goal of this study is to develop a novel rehabilitative method, in chronic stroke, which minimizes residual deficits by maximally utilizing the potential for cortical plasticity.

Despite extensive rehabilitation, approximately 60-80% of patients with stroke experience residual dysfunction of the upper limb. Deficits are believed to linger due to neurophysiologic imbalance between the ipsilesional (stroke-affected) and contralesional (intact) motor cortices. Specifically, the ipsilesional motor cortex loses its normal inhibitory control over the contralesional areas, which, in return, intensify their inhibitory influence upon the former. Constraint-Induced Movement Therapy (CIMT) represents a family of techniques that alleviates residual deficits by rectifying these neurophysiologic imbalances. By reinforcing use of the paretic upper limb in daily life during restraint of the non-paretic limb, CIMT initiates use-dependent neuroplastic reorganization implicating the ipsilesional motor areas, which demonstrate return-of-activity and regain territory in the surviving regions, mitigating the exaggerated inhibitory influence exerted by the contralesional areas.

Despite promising evidence, however, clinical utility of CIMT is limited due to its labor-intensive protocols and inadequate gains. Our objective is to address gaps in existing clinical rehabilitative research. The investigators propose to 1) combine CIMT with targeted stimulation of the ipsilesional motor cortices, 2) Use a novel, noninvasive method of stimulation, called transcranial direct current stimulation (tDCS), 3) Use multimodal imaging to determine comprehensive mechanisms of recovery in patients. Our central hypotheses are 1) ipsilesional motor cortices would be an ideal site for delivering stimulation during CIMT, 2) tDCS will be easy, safe and inexpensive to apply and will target multiple maps concurrently during rehabilitation as demonstrated in our elemental research. 3) structural and functional imaging methods will demonstrate complementary cortical, corticospinal and cortico-muscular markers of recovery.

Study Timeline

• Study Start: 2011-07
• Study First Submitted: 2012-02-16
• Study First Submitted QC: 2012-02-21
• Study First Posted: 2012-02-27
• Primary Completion: 2019-12
• Study Completion: 2019-12
• Status Verified: 2020-07
• Last Update Submitted: 2020-07-14
• Last Update Posted: 2020-07-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 67

Inclusion Criteria

• Diagnosed with stroke that occurred at least 6 months ago

Exclusion Criteria

• Pregnant
• Ongoing use of Central Nervous System activating medications
• Presence of an electrically, magnetically or mechanically activated implant, including cardiac pacemaker, cochlear implant
• Metal in the head
• A history of medication-resistant epilepsy in the family
• Past history of seizures or unexplained spells of loss of consciousness

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
tDCS plus CIMT	Constraint induced movement therapy (CIMT)	Patients with stroke affecting the hand will receive Constraint-induced movement therapy (CIMT) concurrent with tDCS: noninvasive brain stimulation. TDCS will be applied to areas of the brain responsible for movement of the affected hand. This combination of tDCS and CIMT will be delivered for 1 hr each day for 3 days a week for 5 weeks. Patients will also be asked to use their affected hand in daily activities at home for 5 hrs a day while wearing a mitt on the unaffected hand.
Sham tDCS plus CIMT	Constraint induced movement therapy (CIMT)	Subjects in this group will be trained on Constraint induced movement therapy (CIMT) for the hand while concurrently receiving placebo noninvasive brain stimulation (tDCS). They will be receiving Sham tDCS: placebo noninvasive brain stimulation. They will be provided treatment for 3 days a week for 5 weeks for 1 hr each day at the Cleveland Clinic. They would be asked to use affected hand in daily activities for 5 hrs everyday at home while wearing a mitt on their unaffected hand.

Primary Outcome Measures

Name	Time	Method
Change in Upper limb function following combination of tDCS with CIMT	Each patient will be given the assessment tests at 3 points during the study, at baseline, interim test (an average of 2.5 weeks from baseline) and at posttest (an average of 5 weeks from baseline).	To address the functional advantage of combining tDCS and CIMT tests that evaluate impairments of the hand will be utilized. Also, change in ability to carry out activities of daily living will be measured.

Secondary Outcome Measures

Name	Time	Method
Study of change in neural mechanisms that underlie the complementary association of cortical stimulation and CIMT	Each patient will be given the assessment tests at 3 points during the study, at baseline, interim test (an average of 2.5 weeks from baseline) and at posttest (an average of 5 weeks from baseline)	To identify the underlying neural mechanisms in the association of cortical stimulation and CIMT, the patient will undergo structural and functional magnetic resonance imaging (MRI) and tests of neurophysiology.

Trial Locations

Locations (1)

The Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States