Combined Neural and Behavioral Therapies to Enhance Stroke Recovery

NCT ID: NCT00929656

Last Updated: 2017-08-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-01
• Study Completion Date: 2015-09-30

Brief 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.

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.

Conditions

Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Real rTMS

Real rTMS + unimanual paretic UE training

Group Type: EXPERIMENTAL

Real rTMS

Intervention Type: PROCEDURE

rTMS application to lesioned hemisphere; 10 Hz, 1000 pulses

Unimanual paretic UE Training

Intervention Type: PROCEDURE

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)

Sham rTMS

Sham rTMS + unimanual paretic UE training

Group Type: ACTIVE_COMPARATOR

Sham rTMS

Intervention Type: PROCEDURE

sham rTMS application to lesioned hemisphere; 10 Hz, 1000 pulses

Unimanual paretic UE Training

Intervention Type: PROCEDURE

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)

Interventions

Real rTMS

rTMS application to lesioned hemisphere; 10 Hz, 1000 pulses

Intervention Type: PROCEDURE

Sham rTMS

sham rTMS application to lesioned hemisphere; 10 Hz, 1000 pulses

Intervention Type: 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)

Intervention Type: PROCEDURE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dorian Kay Rose, PhD MS BS

Role: PRINCIPAL_INVESTIGATOR

North Florida/South Georgia Veterans Health System, Gainesville, FL

Locations

North Florida/South Georgia Veterans Health System, Gainesville, FL

Gainesville, Florida, United States

Countries

United States

Other Identifiers

B6862-W

Identifier Type: -

Identifier Source: org_study_id