Combined Neural and Behavioral Therapies to Enhance Stroke Recovery

Stroke Clinical Trial

Official title:

Combining Neural and Behavioral Therapies to Enhance Stroke Recovery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00929656
• Other study ID #: B6862-W
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: June 25, 2009
• Last updated: May 31, 2016
• Start date: August 2010
• Est. completion date: November 2015

Study information

• Verified date: May 2016
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

Stroke is the leading cause of long-term disability in this country with more than 1 million Americans reporting difficulty with daily activities. Loss of independence in self-care tasks is primarily due to limited recovery of the arm. This study will determine if the addition of Transcranial Magnetic Stimulation (TMS) to excite the lesioned hemisphere (side of the brain affected by the stroke), to progressive functional task exercise either of the weakened arm alone or of both arms together will improve arm recovery to a greater degree than one of these two types of arm exercise alone. Individuals post-stroke will participate in 16 sessions of 1) arm rehabilitation alone (with the weaker arm only or with both arms together) or 2) arm rehabilitation plus TMS. The investigators will assess arm movement ability and function immediately following the 4-week intervention and at a 30-day follow-up to determine retention of immediate gains. The investigators hypothesize that those who receive TMS as an adjuvant will have improved arm movement ability than those who only exercise.

Description:

Limited recovery of upper extremity (UE) function post-stroke continues to be one of the greatest challenges faced in neurorehabilitation. There is an urgent unmet need to identify effective approaches to drive UE recovery in this population. In response to this challenge, the overall purpose of this proposed research plan is to develop rehabilitation interventions that restore UE motor recovery. Contemporary approaches to motor rehabilitation are based on evidence that behavioral experience drives cortical reorganization following neural injury. Although the rationale of driving the damaged motor cortex by focused training of the paretic UE appears straightforward, and has historically been the focus of rehabilitation, functional recovery remains limited. There remains a gap between this central neurobiological change and a meaningful behavioral change. There is a need, therefore, to augment or potentiate behavioral experience. This proposal will address this gap by examining two potential drivers of the lesioned hemisphere: 1) the non-lesioned hemisphere via engagement of the unaffected UE in behavioral training and 2) stimulation of the lesioned hemisphere via repetitive Transcranial Magnetic Stimulation (rTMS). This proposal builds on the foundation of the applicant's previous work which suggested that the contralesional, intact, hemisphere could be used to drive the lesioned hemisphere through bimanual movement. Additionally, it is possible to drive the lesioned hemisphere externally using rTMS to enhance cortical stimulation. Thus, pairing externally-driven enhancement of cortical excitability with internally-driven activation of the intact hemisphere during bilateral movements could combine to further increase excitability in the lesioned hemisphere and manifest improved movement capability of the paretic UE. The fundamental hypothesis guiding this proposal is that increased excitability of the lesioned cortex will improve behavioral function of the paretic UE post-stroke. To investigate the overall hypothesis the investigators will examine these drivers of cortical excitability and their role in UE recovery by addressing the following aims:

Specific Aim 1. Determine the magnitude of difference in central and behavioral changes in individuals with post-stroke hemiparesis randomized to a bilateral versus unilateral UE motor training program.

Specific Aim 2a. Determine the magnitude of difference in central and behavioral changes in individuals with post-stroke hemiparesis randomized to behavioral UE training compared to behavioral UE training + rTMS.

Specific Aim 2b. Determine the differential effects of rTMS on bilateral behavioral training compared to unilateral behavioral training as measured both centrally and behaviorally in individuals with post-stroke hemiparesis Post-stroke upper limb paresis and resultant loss of functional ability continues to present a barrier to those post-stroke in returning to full societal participation. Interventions that directly target the mechanism of hemiparesis, including decreased excitability of the lesioned hemisphere, are most likely to promote true recovery as opposed to the oft observed functional compensation in these individuals.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: November 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Diagnosis of 1st stroke > 6 months

• Sub-cortical stroke confirmed with CT or MRI

• Passive range of motion in bilateral shoulder and elbow within functional limits

• UE Fugl-Meyer shoulder/elbow subcomponent score between 15 - 25

• 18-80 years of age

Exclusion Criteria:

• Use of medications that may lower seizure threshold

• History of epilepsy, brain tumor, learning disorder, mental retardation, drug or alcohol abuse, dementia, major head trauma, or major psychiatric illness

• evidence of epileptiform activity on EEG obtained before beginning treatment

• history or radiographic evidence of arteriovenous malformation, intracortical hemorrhage, subarachnoid hemorrhage, or bilateral cerebrovascular disease,

• history of cortical stroke

• history of implanted pacemaker or medication pump, metal plate in skull, or metal objects in the eye or skull

• pregnancy

• pain in either upper extremity that would interfere with movement

• unable to understand 3-step directions

• orthopedic condition in back or UE or impaired corrected vision that would alter kinematics of reaching

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Stroke

Intervention

Procedure:
• Unimanual UE training + rTMS
rTMS application to lesioned hemisphere followed by unimanual (paretic) UE exercise (100 repetitions) for 16 sessions (4 sessions/week for 4 weeks)
• Unimanual UE training + sham rTMS
sham rTMS application to lesioned hemisphere followed by unimanual (paretic) UE exercise (100 repetitions) for 16 sessions (4 sessions/week for 4 weeks)

Locations

Country	Name	City	State
United States	North Florida/South Georgia Veterans Health System, Gainesville, FL	Gainesville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Wolf Motor Function Test		Post-intervention and 30 days post-intervention	No
Secondary	Reach Path Ratio of Paretic UE during a reach to point task		Post-intervention and 30 days post-intervention	No
Secondary	Muscle onset time relative to movement initiation of the paretic UE during a reach to point task		Post-intervention and 30 days post-intervention	No
Secondary	Motor Evoked Potential of paretic UE muscle		Post-intervention and 30 days post-intervention	No
Secondary	Slope of the Input-Output Recruitment Curve		Post-intervention and 30 days post-intervention	No
Secondary	Short intracortical facilitation of lesioned hemisphere		Post-intervention and 30 days post-intervention	No