CUped: An Approach to Motor Recovery Post-Stroke, Not Compensation

NCT06329765 | Recruiting

• 1 other identifier: HR- 4380
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of lower limb rehabilitation after stroke is recovery of independent walking at home and in the community. Few stroke survivors achieve this goal. Suboptimal outcomes are due to the serious and intransigent nature of movement impairments caused by stroke and the scarcity of feasible and effective therapies that restore movement lost to stroke. Our team has developed a novel exercise intervention called CUped (pronounced cupid, like the Roman god) to address barriers to recovery and improve walking after stroke. CUped is so called because it compels use of the paretic limb during a movement that resembles pedaling. This project will examine safety, acceptability, and tolerance to CUped, characterize its therapeutic effects, and identify dose-response relationships. Results will provide preliminary data for an R01 to support a randomized controlled trial (RCT). CUped is designed to help stroke survivors recover lower limb movement lost to stroke, thereby improving walking. It is intended to be used as an adjunct to gait training. CUped uses a robotic technology that eliminates compensatory movements that interfere with recovery, compels use of the paretic lower limb, and targets 3 key movement impairments caused by stroke: decreased muscle output from the paretic limb, inappropriate paretic muscle timing, and abnormal interlimb coordination. Exercise is done in sitting which enables high repetition practice. Like walking, CUped requires continuous, reciprocal use of both lower limbs; effects are likely to transfer to walking. The risk-reward profile of this proposal is ideal for an R21, which is an NIH funding opportunity intended to encourage exploratory/developmental research by providing support for the early and conceptual stages of project development. CUped is a novel therapy grounded in a physiologic premise and based on prior observations from our laboratory. The investigators have pilot data suggesting that CUped fulfills its design specifications, and this study will be the first to test its therapeutic effects. In this Stage 1 rehabilitation trial, The investigators will support or quickly refute the hypothesis that CUped is safe, acceptable, and capable of eliciting a therapeutic response in stroke survivors. The investigators will also examine tolerance to CUped and dose-response effects. If our hypotheses are supported, the investigators will be poised to run an RCT to isolate the effects of CUped and compare them to standard care. Future work will investigate physiologic mechanisms underlying the effects of CUped.

Conditions

Stroke; Hemiplegia

Outcome Measures

Primary Outcomes (7)

• Paretic limb use in walking

  Propulsive impulse generated by the paretic limb during overground walking measured from biomechanical gait analysis.

  Pretest (1 day to 1 month before the intervention begins), Posttest (typically within 1 week of completing the intervention) and Midpoint of training (week 3)

• Paretic limb use in pedaling

  Mechanical work generated by the paretic limb during conventional pedaling measured from force-sensitive pedals.

  Each training day, up to 24 times, through study completion which takes 6-8 weeks.

• Interlimb coordination in walking

  Interlimb phasing of paretic and non-paretic limb during overground walking measured from biomechanical gait analysis.

  Pretest (1 day to 1 month before the intervention begins), Posttest (typically within 1 week of completing the intervention) and Midpoint of training (week 3)

• Interlimb coordination in pedaling

  Relative phasing of paretic and non-paretic limb during split-crank (i.e., bilateral uncoupled) pedaling calculated from position encoders coupled to right and left pedal.

  Each training day, up to 24 times, through study completion which takes 6-8 weeks.

• Motorized intervention during pedaling split-crank (i.e., bilateral uncoupled) pedaling

  Magnitude of assistance and resistance applied to the moving limbs during split-crank (i.e., bilateral uncoupled) pedaling measured as electrical current to the motors converted to units of torque.

  Each training day, up to 24 times, through study completion which takes 6-8 weeks.

• Absences

  Count the number times each participant misses a scheduled training session. Record the reason for the absence.

  Each day of training. There are 24 training sessions delivered over 6 weeks.

• Adverse events

  Count the number of adverse events, defined as any undesirable experience associated with CUped. Classify as mild, moderate, or severe. Classify by attribution as unrelated to protocol, possibly, probably, or definitely related to protocol.

  Each day of training. There are 24 training sessions delivered over 6 weeks.

Secondary Outcomes (5)

• Muscle activity - timing

  Pretest (1 day to 1 month before the intervention begins), Posttest (typically within 1 week of completing the intervention) and Midpoint of training (week 3)

• Muscle activity - amplitude

  Pretest (1 day to 1 month before the intervention begins), Posttest (typically within 1 week of completing the intervention) and Midpoint of training (week 3)

• Physiological response to exercise - Blood pressure

  Each training day, up to 24 times, through study completion which takes 6-8 weeks.

• Physiological response to exercise - Heart rate

  Each training day, up to 24 times, through study completion which takes 6-8 weeks.

• Physiological response to exercise - Rate of perceived exertion

  Each training day, up to 24 times, through study completion which takes 6-8 weeks.

Study Arms (1)

Exercise with CUped

EXPERIMENTAL

Participants will exercise with CUped (a motor-assisted, split crank pedaling device) and undergo 50 m of gait training. CUped comprises a left and right pedal; each is attached to the shaft of a motor. There is no mechanical connection between pedals. Participant's feet are secured to the pedals. They are asked to pedal forward and keep the legs 180° out-of-phase. The position of the left and right cranks is monitored. When the phase relationship is not maintained, motors provide torque to assist the lagging limb and resist the leading limb. Motors are under feedback control. Torque is proportional to the magnitude and sign of the error.

Behavioral: Exercise with CUped - a motor-assisted, split crank pedaling device and undergo 50 m of gait training.

Interventions

Exercise with CUped - a motor-assisted, split crank pedaling device and undergo 50 m of gait training. BEHAVIORAL

Exercise with CUped - a motor-assisted, split crank pedaling device and undergo 50 m of gait training.

Also known as: Exercise with CUped

Exercise with CUped

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Single, unilateral stroke in adulthood.
• Cortical, subcortical stroke. Individuals with cortical lesions affecting sensory and motor structures in the gray matter of the brain will be included. Individuals subcortical white matter lesions affecting the internal capsule and corona radiata will be included.
• Ischemic, hemorrhagic stroke. Individuals with ischemic and hemorrhagic strokes will be admitted. Because ischemic stroke is more common than hemorrhagic, the investigators expect a smaller proportion of volunteers from the latter group.
• Chronic stroke. Individuals with chronic stroke, defined as \>6 months post infarct, will be included.
• Able to walk 10 m. Stroke survivors capable of walking 10 m overground will be admitted. Canes, walkers, braces, and other devices will be allowed. This study examines the effect of CUped on gait kinematics and kinetics; therefore, the ability to walk is imperative.
• Unilateral motor impairment consistent with hemiparesis.
• Learned non-use of the paretic limb. Non-use will be verified by comparing paretic limb work (W) during unilateral and bilateral coupled pedaling. Participants with non-use will be identified as those who produce significantly \<50% of the total W of bilateral coupled pedaling with their paretic limb but are capable of unilateral pedaling with the paretic limb at a workload equivalent to 50% of the total W of bilateral coupled pedaling. (Significance will be determined using a 1-sample t-test or corresponding non-parametric test in the case of non-normality).
• No contraindications for exercise. Contraindications to exercise include but may not be limited to recent electrocardiogram changes or recent myocardial infarction, uncontrolled arrhythmia, unstable angina, third degree heart block, acute progressive heart failure, uncontrolled hypertension, and orthopedic conditions (e.g., severe muscle contracture, arthritis, acute limb injury) that may interfere with pedaling.
• Age ≥18. All participants must be at least 18 years of age. The investigators are studying adult not childhood stroke. Recovery mechanisms are different between adult and childhood stroke survivors.
• Able to commit to 27 visits to the lab (pre-, mid-, post-test, plus 24 training sessions).

You may not qualify if:

• More than 1 stroke. Individuals with more than one clinically apparent stroke, as evidenced by residual impairments and/or medical imaging, will be excluded. Individuals with history of transient ischemic attack (TIA) resulting in no residual impairments or brain damage will NOT be excluded.
• Stroke in the cerebellum or basal ganglia. Individuals with stroke affecting primarily the cerebellum or basal ganglia will be excluded. The cerebellum has an important role in motor learning. Given that CUped depends on motor learning, people with cerebellar strokes may not benefit. Basal ganglia strokes can cause tremor, which is not the target of CUped. However, individuals with predominantly internal capsule lesions that also affect the basal ganglia will be included.
• Dementia or other cognitive impairment that interferes with learning and/or the ability to consent.
• Orthopedic impairments that interfere with pedaling.
• Cardiovascular contraindications to exercise.
• Inability to walk 10 m overground. Participants will be excluded in they are not able to walk 10 m overground our cannot do so safely.
• Neurological disorder other than stroke. Individuals with history or signs of any neurologic disease or injury other than stroke will be excluded. Such conditions may include head trauma, cerebral palsy, epilepsy, brain tumor, diabetic neuropathy, dementia, multiple sclerosis, Parkinson's disease, or Alzheimer's disease.

Sponsors & Collaborators

• Marquette University: lead
• Medical College of Wisconsin: collaborator

Study Sites (1)

Marquette University

Milwaukee, Wisconsin, 53201, United States

RECRUITING

MeSH Terms

Conditions

Stroke; Hemiplegia

Interventions

Exercise

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Paralysis; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Single group pretest-posttest

Study Record Dates

• First Submitted: October 6, 2023
• First Posted: March 26, 2024
• Study Start: August 7, 2023
• Primary Completion: April 4, 2026
• Study Completion (Estimated): April 4, 2027
• Last Updated: September 30, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)