Combined Neural and Behavioral Therapies to Enhance Stroke Recovery

Combining Neural and Behavioral Therapies to Enhance Stroke Recovery

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.

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Procedure: Real rTMS; Procedure: Unimanual paretic UE Training; Procedure: Sham rTMS

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32608
      • North Florida/South Georgia Veterans Health System, Gainesville, FL

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Real rTMS; Real rTMS + unimanual paretic UE training	Procedure: Real rTMS; rTMS application to lesioned hemisphere; 10 Hz, 1000 pulses; Procedure: Unimanual paretic UE Training; UE exercise for 4 hours (two hours 1:1 with therapist and two hours independent at home) for 16 sessions (4 sessions/week for 4 weeks)
Active Comparator: Sham rTMS; Sham rTMS + unimanual paretic UE training	Procedure: Unimanual paretic UE Training; UE exercise for 4 hours (two hours 1:1 with therapist and two hours independent at home) for 16 sessions (4 sessions/week for 4 weeks); Procedure: Sham rTMS; sham rTMS application to lesioned hemisphere; 10 Hz, 1000 pulses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wolf Motor Function Test Change	Change, in seconds, between Pre-intervention and post-intervention (4 wks following pre-intervention). The time to complete 15 separate upper extremity functional tasks are recorded. These 15 separate timed events are averaged to provide one time, in seconds. This is considered an Activity Measure on the WHO ICF model.	Change between Pre-intervention (baseline) to Post-intervention (4 wks following pre-intervention)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Upper Extremity Fugl-Meyer Motor Assessment Change	Change in Score from Pre-intervention to Post-Intervention. This outcome measures arm motor control; the ability to move outside of pathologic synergistic patterns. It is a measure of impairment in Body Structure/Function. Total score ranges from 0-66, with 0 indicative of no movement and 66 considered normal motor control.	Change Between Pre-intervention (baseline) to Post-intervention (4 wks following pre-intervention)
Grip Strength Change	Change in Paretic hand grip strength from pre- to post-intervention. Grip strength measured by hand-held dynamometer. An average of 3 5-second trials was used for analysis.	Change between Pre-intervention (baseline) to Post-intervention (4 wks following pre-intervention)
Motor Activity Log - Amount of Use Change	Self-Report Amount of Use of Paretic UE to complete 30 functional tasks. Each task is reported on a 0-5 scale with "0" representing "did not use my paretic hand at all for that task" and "5" representing "I used my paretic hand as much as before the stroke to complete that task." A "5" on each task would be considered "normal."	Change Between Pre-intervention (baseline) to Post-intervention (4 wks following pre-intervention)
Motor Activity Log - How Well Change	Self-Report of How Well paretic UE performed completing 30 functional tasks. Each task is reported on a 0-5 scale with "0" representing "Unable to use my paretic hand to perform that task" and "5" representing "My paretic hand performs that task as well as it did before the stroke." A "5" on each task would be considered "normal."	Change between Pre-intervention (baseline) to Post-intervention (4 wks following pre-intervention)

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Dorian Kay Rose, PhD MS BS, North Florida/South Georgia Veterans Health System, Gainesville, FL

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): September 30, 2015
• Study Completion (Actual): September 30, 2015

Study Registration Dates

• First Submitted: June 25, 2009
• First Submitted That Met QC Criteria: June 26, 2009
• First Posted (Estimate): June 29, 2009

Study Record Updates

• Last Update Posted (Actual): August 21, 2017
• Last Update Submitted That Met QC Criteria: July 12, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Rehabilitation; Upper Extremity; Neurophysiology
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke
• Other Study ID Numbers: B6862-W