Stroke
Conditions
Keywords
aerobic exercise, physical therapy, occupational therapy
Brief summary
Traditional rehabilitation approaches are time and personnel intensive and costly, and leave \ 75% of stroke survivors with residual disability. We propose a clinical trial to determine effects of forced aerobic exercise (FE; i.e., mechanically supplemented) in facilitating upper and lower extremity motor recovery post-stroke in an outpatient rehabilitation setting, to elucidate neural and biochemical substrates of FE-induced motor recovery, and to evaluate cost effectiveness of a FE-centered intervention compared to traditional stroke rehabilitation. The global effect of FE has the potential to enhance recovery in a growing population of stroke survivors in a cost-effective manner, thus accelerating its clinical acceptance.
Detailed description
Traditional rehabilitation approaches following stroke involve 1:1 motor learning-based training to facilitate recovery of upper extremity (UE) and lower extremity (LE) function. These time- and personnel-intensive approaches are costly, yet leave \ 75% of stroke survivors with residual disability. More effective alternative approaches to facilitate motor recovery following stroke have not been adopted clinically due to excessive time and cost. To advance clinical care, both effectiveness and cost of a candidate intervention must be considered simultaneously. Aerobic exercise (AE) is known to improve cardiovascular function following stroke and central nervous system (CNS) function in older adults and neurological populations. Strong theoretical arguments suggest that AE may facilitate motor recovery following stroke. A protocol that rigorously tests this theory in the subacute stroke population is warranted. Animal studies, coupled with our preliminary data, indicate a specific type of exercise - forced aerobic exercise (FE), where volitional movements are mechanically supplemented - improves motor recovery following stroke. The mechanical assistance provided by FE enables patients to achieve a more rapid and consistent exercise pattern beyond their volitional capabilities while maintaining their aerobic effort within a beneficial range. In our initial studies, persons completing FE cycling followed by a reduced dose of UE motor task practice exhibited greater recovery of UE motor function compared to those completing unassisted AE and motor task practice or extended sessions of motor task practice alone. Animal studies have shown that FE triggers the release of brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1), thought to be critical building blocks for neuroplasticity. Project Hypothesis: FE facilitates high-intensity AE, which triggers growth factors essential for neuroplasticity, thereby 'priming' the CNS to facilitate motor recovery associated with motor retraining therapies. We propose a prospective, pragmatic clinical trial to determine effects of FE in facilitating UE and LE motor recovery post-stroke in an outpatient rehabilitation setting, to elucidate neural and biochemical substrates of FE-induced motor recovery, and to evaluate cost effectiveness of a FE-centered intervention compared to traditional stroke rehabilitation. Aim 1: Determine effects of FE+rehab vs. time-matched rehab on the recovery of UE motor function. Aim 2: Determine effects of FE+rehab vs. time-matched rehab on recovery of lower extremity motor function. Aim 3: Determine effects of FE+rehab vs. rehab on electrophysiological and biochemical markers of neuroplasticity. Aim 4: Evaluate cost-effectiveness of FE+rehab vs. rehab. The global effect of FE has the potential to enhance recovery in a growing population of stroke survivors in a cost-effective manner, thus accelerating its clinical acceptance. Our mechanistic aim will elucidate the effects of each approach on substrates underlying neuroplasticity.
Interventions
BEHAVIORALForced Rate Exercise + Rehab
The FE+rehab group (N=33) will complete FE on the cycle designed to augment pedaling rate to \>75 RPM. Target heart rate zone will be set to 60-80% of HR reserve. The session will consist of a 5-min warm-up, 35-min main exercise set, and 5-min cool down. Following FE, abbreviated sessions of motor learning-based training will be administered by a neurologic OT and PT experienced in stroke rehabilitation, with 30 min focused on restoration of UE function (OT) and 15 min focused on LE motor function/ gait training (PT).
BEHAVIORALRehabilitation
The rehab group will receive consecutive, full-length sessions of motor learning-based training, administered by a neurologic OT and PT experienced in stroke rehabilitation, with 45 min focused on restoration of UE function (OT) and 45 min focused on LE motor function/ gait training (PT).
Sponsors
The Cleveland Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Outcomes assessor will be blinded to group allocation
Intervention model description
prospective, single-center, parallel group, rater-blind, pragmatic randomized clinical trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Sixty-six individuals with chronic stroke able to provide informed consent who meet the following criteria for inclusion will be recruited from the Cleveland Clinic: 1. 3-9 months following single ischemic or hemorrhagic stroke confirmed with neuroimaging (ie: first-time stroke) 2. Fugl-Meyer motor score 19-55 in the involved UE 3. Fugl-Meyer score \<34 in the involved LE demonstrating residual hemiparesis 4. Ambulatory ≥ 20 meters with no more than contact guard assistance 5. 18-85 years of age
Exclusion criteria
include: 1. hospitalization for myocardial infarction, heart failure or heart surgery within 3 months 2. cardiac arrhythmia 3. hypertrophic cardiomyopathy 4. history of multiple strokes 5. actively undergoing physical or occupational therapy or enrolled in another interventional study 6. severe aortic stenosis 7. untreated deep vein thrombosis or pulmonary embolus 8. unstable angina 9. uncontrolled hypertension 10. implanted pacemaker or defibrillator 11. dyspnea at rest 12. clinically significant neurologic condition/diagnosis other than stroke 13. recent history of elicit drug or alcohol misuse or significant mental health illness 14. significant contractures 15. anti-spasticity injection within 3 months of enrollment 16. skull hardware (e.g. screws/plates) or prior craniotomies that could shunt current flow altering EEG measures 17. other contraindication to exercise or EEGs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Upper Extremity Fugl-Meyer Motor Assessment | Baseline to end of treatment at 12 weeks and end of treatment + 6 months | Impairment-based measure of the upper extremity post-stroke. |
| Gait Velocity | Baseline to end of treatment at 12 weeks and end of treatment + 6 months | Gait velocity obtained using motion capture. |
| Plasma IGF-1 | Before and after first and 24th treatment session | Blood biomarker for neuroplasticity |
| Serum BDNF | Before and after first and 24th treatment session | Blood biomarker for neuroplasticity |
| electroencephalograms | Baseline and end of treatment at 12 weeks | Electroencephalograms will be obtained to determine the degree of active engagement of different cortical areas during active/passive UE and LE movements |
| Incremental cost-effectiveness ratio | baseline to end of treatment at 12 weeks and baseline to end of treatment + 6 months | Incremental cost-effectiveness ratio (ICER) expressed as cost per quality of life years (QALY) will be computed using a healthcare perspective. |
| Stroke Impact Scale | Baseline to end of treatment at 12 weeks and end of treatment + 6 months | Self-reported quality of life measure, normalized to a score from 0-100 with higher scores indicative of better self-reported quality of life |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Action Research Arm Test | Baseline to end of treatment at 12 weeks and end of treatment + 6 months | Measure of upper extremity gross and fine motor function post-stroke |
| Biomechanical Dexterity Task | Baseline to end of treatment at 12 weeks and end of treatment + 6 months | Force tracking task - accuracy within targeted range |
| Biomechanical measure of maximum grasp force | Baseline to end of treatment at 12 weeks and end of treatment + 6 months | maximum grasp force measured with force transducer |
| Bimanual Dexterity Task | Baseline to end of treatment at 12 weeks and end of treatment + 6 months | Time to complete task when separating 2 force transducers |
| Six minute walk test | Baseline to end of treatment at 12 weeks and end of treatment + 6 months | Measure of walking capacity |
| Lower Extremity Fugl-Meyer Motor Assessment | Baseline to end of treatment at 12 weeks and end of treatment + 6 months | Impairment-based measure of the lower extremity post-stroke. |
| Biomechanical Gait Analysis | Baseline, end of treatment at 12 weeks, end of treatment + 6 months | Biomechanical assessment of the following spatio-temporal components of gait using motion capture: % of gait cycle spent in swing and stance phases, and in single and double limb support. |
| Plasma BDNF | Before and after first and 24th session | Blood biomarker for neuroplasticity |
| Somatosensory evoked potentials | Baseline | lower extremity somatosensory evoked potentials |
| Modified Rankin Scale | Baseline to end of treatment at 12 weeks and end of treatment + 6 months | Measure of disability |
| Peak oxygen consumption (Peak VO2) | Baseline to end of treatment at 12 weeks | Measure of cardiorespiratory function |
| Patient-Reported Outcomes Measurement Information System (PROMIS) Computerized Adaptive Test (CAT) v 2.0 Physical Function | Baseline to end of treatment at 12 weeks and end of treatment + 6 months | Self-reported quality of life measure of physical function computed as normalized T-scores (1-100 range), with higher scores indicative of greater self-reported quality of life |
| Patient-Reported Outcomes Measurement Information System (PROMIS) Computerized Adaptive Test (CAT) v 2.0 Ability to Participate in Social Roles | Baseline to end of treatment at 12 weeks and end of treatment + 6 months | Self-reported quality of life measure computed as a normalized T-score (0-100 range), with higher scores indicative of greater self-reported participation |
Countries
United States
Contacts
CONTACTCourtney Miller, PT, DPT
CONTACTDonayja Harris, BS
PRINCIPAL_INVESTIGATORSusan Linder, PT, DPT, PhD
The Cleveland Clinic
Outcome results
None listed