Stroke
Conditions
Keywords
Rehabilitation, Neurophysiology, Upper Extremity
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.
Interventions
PROCEDUREReal rTMS
rTMS application to lesioned hemisphere; 10 Hz, 1000 pulses
PROCEDURESham rTMS
sham rTMS application to lesioned hemisphere; 10 Hz, 1000 pulses
PROCEDUREUnimanual 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)
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Wolf Motor Function Test Change | Change between Pre-intervention (baseline) to Post-intervention (4 wks following pre-intervention) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Upper Extremity Fugl-Meyer Motor Assessment Change | Change Between Pre-intervention (baseline) to Post-intervention (4 wks following pre-intervention) | 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. |
| Grip Strength Change | Change between Pre-intervention (baseline) to Post-intervention (4 wks following pre-intervention) | 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. |
| Motor Activity Log - Amount of Use Change | Change Between Pre-intervention (baseline) to Post-intervention (4 wks following pre-intervention) | 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. |
| Motor Activity Log - How Well Change | Change between Pre-intervention (baseline) to Post-intervention (4 wks following pre-intervention) | 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. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the Malcom Randall VA Brain Rehabilitation Research Center database from 2/1/13-9/30/15
Participants by arm
| Arm | Count |
|---|---|
| Unimanual UE Training + Real rTMS Participants randomized to the Experimental Arm received real rTMS (1000 pulses) to their ipsilesional hemisphere followed by two hours of paretic arm functional task practice administered/supervised by a physical therapist. | 13 |
| Unimanual UE Training + Sham rTMS Participants randomized to the Placebo Arm received sham rTMS to their ipsilesional hemisphere followed by two hours of paretic arm functional task practice administered/supervised by a physical therapist. | 9 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | Unimanual UE Training + Real rTMS | Unimanual UE Training + Sham rTMS | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 3 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 6 Participants | 15 Participants |
| Age, Continuous | 61.3 years STANDARD_DEVIATION 10 | 59.4 years STANDARD_DEVIATION 8.2 | 60.5 years STANDARD_DEVIATION 9.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 5 Participants | 16 Participants |
| Region of Enrollment United States | 13 Participants | 9 Participants | 22 Participants |
| Sex: Female, Male Female | 1 Participants | 4 Participants | 5 Participants |
| Sex: Female, Male Male | 12 Participants | 5 Participants | 17 Participants |
| Time Post-Stroke | 44.0 months STANDARD_DEVIATION 95.6 | 33.3 months STANDARD_DEVIATION 25.9 | 39.6 months STANDARD_DEVIATION 74.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 13 | 0 / 9 |
| serious Total, serious adverse events | 0 / 13 | 0 / 9 |
Outcome results
Primary
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.
Time frame: Change between Pre-intervention (baseline) to Post-intervention (4 wks following pre-intervention)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Unimanual UE Training + Real rTMS | Wolf Motor Function Test Change | 1.6 seconds | Standard Error 1.1 |
| Unimanual UE Training + Sham rTMS | Wolf Motor Function Test Change | 1.8 seconds | Standard Error 1.2 |
Secondary
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.
Time frame: Change between Pre-intervention (baseline) to Post-intervention (4 wks following pre-intervention)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Unimanual UE Training + Real rTMS | Grip Strength Change | 1.1 kilograms | Standard Error 2 |
| Unimanual UE Training + Sham rTMS | Grip Strength Change | 1.3 kilograms | Standard Error 2.4 |
Secondary
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.
Time frame: Change Between Pre-intervention (baseline) to Post-intervention (4 wks following pre-intervention)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Unimanual UE Training + Real rTMS | Motor Activity Log - Amount of Use Change | 1.3 Units on a scale | Standard Error 0.3 |
| Unimanual UE Training + Sham rTMS | Motor Activity Log - Amount of Use Change | 1.2 Units on a scale | Standard Error 0.3 |
Secondary
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.
Time frame: Change between Pre-intervention (baseline) to Post-intervention (4 wks following pre-intervention)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Unimanual UE Training + Real rTMS | Motor Activity Log - How Well Change | 1.1 Units on a scale | Standard Error 0.3 |
| Unimanual UE Training + Sham rTMS | Motor Activity Log - How Well Change | 1.2 Units on a scale | Standard Error 0.4 |
Secondary
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.
Time frame: Change Between Pre-intervention (baseline) to Post-intervention (4 wks following pre-intervention)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Unimanual UE Training + Real rTMS | Upper Extremity Fugl-Meyer Motor Assessment Change | 5.8 units on a scale | Standard Error 1.4 |
| Unimanual UE Training + Sham rTMS | Upper Extremity Fugl-Meyer Motor Assessment Change | 5.8 units on a scale | Standard Error 1.1 |