I-Score: Intensive Stroke Cycling for Optimal Recovery and Economic Value

The I-Score (Intensive Stroke Cycling for Optimal Recovery and Economic Value) Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Stroke
• Intervention / Treatment: Behavioral: Forced Rate Exercise + Rehab; Behavioral: Rehabilitation

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.

• Study Type: Interventional
• Enrollment (Estimated): 66
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Courtney Miller, PT, DPT; Phone Number: 216 509-7012; Email: millerc5@ccf.org
• Study Contact Backup: Name: Donayja Harris, BS; Phone Number: 216 445-2007; Email: harrisD47@ccf.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
      • Contact: Courtney R Miller, DPT; Phone Number: 216-509-7012; Email: millerc5@ccf.org
      • Contact: Donayja Harris, BS; Email: harrisd47@ccf.org
      • Principal Investigator: Susan M Linder, DPT, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Forced Rate Exercise + Rehabilitation; The forced rate exercise+rehab group (N=33) will complete FE on the cycle designed to augment pedaling rate to >75 revolutions per minute (RPM). Target heart rate zone will be set to 60-80% of heart rate (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).	Behavioral: Forced 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).
Active Comparator: Rehabilitation; 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).	Behavioral: Rehabilitation; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Upper Extremity Fugl-Meyer Motor Assessment	Impairment-based measure of the upper extremity post-stroke.	Baseline to end of treatment at 12 weeks and end of treatment + 6 months
Gait Velocity	Gait velocity obtained using motion capture.	Baseline to end of treatment at 12 weeks and end of treatment + 6 months
Plasma IGF-1	Blood biomarker for neuroplasticity	Before and after first and 24th treatment session
Serum BDNF	Blood biomarker for neuroplasticity	Before and after first and 24th treatment session
electroencephalograms	Electroencephalograms will be obtained to determine the degree of active engagement of different cortical areas during active/passive UE and LE movements	Baseline and end of treatment at 12 weeks
electroencephalograms	Electroencephalograms will be obtained to determine the degree of active engagement of different cortical areas under each cycling condition	Baseline and end of treatment at 12 weeks
electroencephalograms	Electroencephalograms will be obtained to quantify inter-area communication and direction of information flow.	Baseline and end of treatment at 12 weeks
Incremental cost-effectiveness ratio	Incremental cost-effectiveness ratio (ICER) expressed as cost per quality of life years (QALY) will be computed using a healthcare perspective.	baseline to end of treatment at 12 weeks and baseline to end of treatment + 6 months
Stroke Impact Scale	Self-reported quality of life measure, normalized to a score from 0-100 with higher scores indicative of better self-reported quality of life	Baseline to end of treatment at 12 weeks and end of treatment + 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Action Research Arm Test	Measure of upper extremity gross and fine motor function post-stroke	Baseline to end of treatment at 12 weeks and end of treatment + 6 months
Biomechanical Dexterity Task	Force tracking task - accuracy within targeted range	Baseline to end of treatment at 12 weeks and end of treatment + 6 months
Biomechanical measure of maximum grasp force	maximum grasp force measured with force transducer	Baseline to end of treatment at 12 weeks and end of treatment + 6 months
Bimanual Dexterity Task	Time to complete task when separating 2 force transducers	Baseline to end of treatment at 12 weeks and end of treatment + 6 months
Six minute walk test	Measure of walking capacity	Baseline to end of treatment at 12 weeks and end of treatment + 6 months
Lower Extremity Fugl-Meyer Motor Assessment	Impairment-based measure of the lower extremity post-stroke.	Baseline to end of treatment at 12 weeks and end of treatment + 6 months
Biomechanical Gait Analysis	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.	Baseline, end of treatment at 12 weeks, end of treatment + 6 months
Biomechanical Gait Analysis	Biomechanical assessment of gait cadence (steps/minute)	Baseline, end of treatment at 12 weeks, end of treatment + 6 months
Biomechanical Gait Analysis	Biomechanical assessment of stride length	Baseline, end of treatment at 12 weeks, end of treatment + 6 months
Biomechanical Gait Analysis	Biomechanical assessment of the following components of gait kinetics using motion capture: 1) peak anterior-posterior propulsion forces, 2) peak anterior-posterior braking forces, 3) peak vertical ground reaction forces, 4) peak lateral ground reaction forces.	Baseline, end of treatment at 12 weeks, end of treatment + 6 months
Biomechanical Gait Analysis	Biomechanical assessment of the following components of gait kinetics using motion capture: 1) total hip extension moment 2) total knee extension moment, 3) total ankle plantarflexion extension moment	Baseline, end of treatment at 12 weeks, end of treatment + 6 months
Biomechanical Gait Analysis	Biomechanical assessment of the following components of gait kinetics during stance phase using motion capture: 1) total hip extension power 2) total knee extension power, 3) total ankle plantarflexion extension power	Baseline, end of treatment at 12 weeks, end of treatment + 6 months
Biomechanical Gait Analysis	Biomechanical assessment of the following kinematic components of gait using motion capture: hip flexion/extension, knee flexion/extension, ankle plantar- and dorsi-flexion	Baseline, end of treatment at 12 weeks, end of treatment + 6 months
Plasma BDNF	Blood biomarker for neuroplasticity	Before and after first and 24th session
Somatosensory evoked potentials	lower extremity somatosensory evoked potentials	Baseline
Modified Rankin Scale	Measure of disability	Baseline to end of treatment at 12 weeks and end of treatment + 6 months
Peak oxygen consumption (Peak VO2)	Measure of cardiorespiratory function	Baseline to end of treatment at 12 weeks
Patient-Reported Outcomes Measurement Information System (PROMIS) Computerized Adaptive Test (CAT) v 2.0 Physical Function	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	Baseline to end of treatment at 12 weeks and end of treatment + 6 months
Patient-Reported Outcomes Measurement Information System (PROMIS) Computerized Adaptive Test (CAT) v 2.0 Ability to Participate in Social Roles	Self-reported quality of life measure computed as a normalized T-score (0-100 range), with higher scores indicative of greater self-reported participation	Baseline to end of treatment at 12 weeks and end of treatment + 6 months

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Investigators: Principal Investigator: Susan Linder, PT, DPT, PhD, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2024
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): April 1, 2029

Study Registration Dates

• First Submitted: August 27, 2024
• First Submitted That Met QC Criteria: September 3, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Estimated): October 16, 2025
• Last Update Submitted That Met QC Criteria: October 14, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: aerobic exercise; physical therapy; occupational therapy
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Therapeutics; Patient Care; Health Services; Health Care Facilities Workforce and Services; Aftercare; Continuity of Patient Care; Rehabilitation
• Other Study ID Numbers: IRB 23-1262

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No