Clinical trial NCT06585943: I-Score: Intensive Stroke Cycling for Optimal Recovery and Economic Value
Official title: The I-Score (Intensive Stroke Cycling for Optimal Recovery and Economic Value) Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Stroke
Keywords: aerobic exercise
physical therapy
occupational therapy
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
First posted: 2024-09-19
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: prospective, single-center, parallel group, rater-blind, pragmatic randomized clinical trial
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Upper Extremity Fugl-Meyer Motor Assessment
timeFrame: Baseline to end of treatment at 12 weeks and end of treatment + 6 months
measure: Gait Velocity
timeFrame: Baseline to end of treatment at 12 weeks and end of treatment + 6 months
measure: Plasma IGF-1
timeFrame: Before and after first and 24th treatment session
measure: Serum BDNF
timeFrame: Before and after first and 24th treatment session
measure: electroencephalograms
timeFrame: Baseline and end of treatment at 12 weeks
measure: electroencephalograms
timeFrame: Baseline and end of treatment at 12 weeks
measure: electroencephalograms
timeFrame: Baseline and end of treatment at 12 weeks
measure: Incremental cost-effectiveness ratio
timeFrame: baseline to end of treatment at 12 weeks and baseline to end of treatment + 6 months
measure: Stroke Impact Scale
timeFrame: Baseline to end of treatment at 12 weeks and end of treatment + 6 months
Secondary outcomes:
measure: Action Research Arm Test
timeFrame: Baseline to end of treatment at 12 weeks and end of treatment + 6 months
measure: Biomechanical Dexterity Task
timeFrame: Baseline to end of treatment at 12 weeks and end of treatment + 6 months
measure: Biomechanical measure of maximum grasp force
timeFrame: Baseline to end of treatment at 12 weeks and end of treatment + 6 months
measure: Bimanual Dexterity Task
timeFrame: Baseline to end of treatment at 12 weeks and end of treatment + 6 months
measure: Six minute walk test
timeFrame: Baseline to end of treatment at 12 weeks and end of treatment + 6 months
measure: Lower Extremity Fugl-Meyer Motor Assessment
timeFrame: Baseline to end of treatment at 12 weeks and end of treatment + 6 months
measure: Biomechanical Gait Analysis
timeFrame: Baseline, end of treatment at 12 weeks, end of treatment + 6 months
measure: Biomechanical Gait Analysis
timeFrame: Baseline, end of treatment at 12 weeks, end of treatment + 6 months
measure: Biomechanical Gait Analysis
timeFrame: Baseline, end of treatment at 12 weeks, end of treatment + 6 months
measure: Biomechanical Gait Analysis
timeFrame: Baseline, end of treatment at 12 weeks, end of treatment + 6 months
measure: Biomechanical Gait Analysis
timeFrame: Baseline, end of treatment at 12 weeks, end of treatment + 6 months
measure: Biomechanical Gait Analysis
timeFrame: Baseline, end of treatment at 12 weeks, end of treatment + 6 months
measure: Biomechanical Gait Analysis
timeFrame: Baseline, end of treatment at 12 weeks, end of treatment + 6 months
measure: Plasma BDNF
timeFrame: Before and after first and 24th session
measure: Somatosensory evoked potentials
timeFrame: Baseline
measure: Modified Rankin Scale
timeFrame: Baseline to end of treatment at 12 weeks and end of treatment + 6 months
measure: Peak oxygen consumption (Peak VO2)
timeFrame: Baseline to end of treatment at 12 weeks
measure: Patient-Reported Outcomes Measurement Information System (PROMIS) Computerized Adaptive Test (CAT) v 2.0 Physical Function
timeFrame: Baseline to end of treatment at 12 weeks and end of treatment + 6 months
measure: Patient-Reported Outcomes Measurement Information System (PROMIS) Computerized Adaptive Test (CAT) v 2.0 Ability to Participate in Social Roles
timeFrame: Baseline to end of treatment at 12 weeks and end of treatment + 6 months
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Susan Linder, PT, DPT, PhD
role: PRINCIPAL_INVESTIGATOR
References: