Robotic Pedaling Therapy for Targeted Neural Plasticity

The aim of this Pilot study is to determine whether robotically targeted lower-limb pedaling therapy can increase the extent of stroke recovery on behavioral measures and induce brain plasticity as measured by functional magnetic resonance imaging (fMRI). Forty (40) adult stroke patients and 80 healthy controls will be enrolled in this study. Of the 40 patients, half will be randomly assigned to the robotically-targeted training ("robotic") group and will receive training on the targeted training task. The other half of the patients will perform a duration-matched aerobic pedaling exercise ("control" group). All stroke patients will be scanned before and after their training program while performing or imagining simple motor tasks. Behavioral assessments of motor and cognitive capacities will be collected at each timepoint. Healthy control subjects enrolled for device testing (20) will receive up to 5 training sessions in a modified robotic paradigm and 1 fMRI scan, in order to investigate motor learning and brain activity in a novel motor control task. Additional healthy pilot subjects (up to 60) will test training protocols and assessments during preparatory design phases of the project.

Study Overview

• Status: Terminated
• Conditions: Stroke
• Intervention / Treatment: Device: Robotic therapy; Device: Aerobic therapy

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53706
      • University of Wisconsin, Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Patients:

Inclusion criteria:

• Subjects will be stroke patients with persistent moderate unilateral lower extremity deficits, age 50-85 years at time of enrollment.
• Time since stroke will be greater than 6 months ("chronic" stroke survivors).
• Persistent moderate unilateral lower-limb impairment (defined as NIH Stroke Scale - Motor Leg section score of 1-2, to be discussed with the patient verbally during phone screening and assessed by the investigator during the initial enrollment visit).
• Fluent in spoken and written English

Exclusion criteria:

• Allergy to electrode gel, surgical tape and metals.
• Subjects under treatment for infectious diseases will be excluded from the study.
• Women who are pregnant or planning to become pregnant during the course of the study will be excluded.
• Contraindications for MRI
• Age over 85 years at time of enrollment.

Healthy Controls:

Inclusion criteria:

• Ages 18-85 years
• Non-Stroke Group 1 ("Matched Controls"): 50-85 years old at time of enrollment, to match the population of stroke patients to be studied
• Non-Stroke Group 2 ("Pilot Controls"): 18-50 years old at time of enrollment (Pilot subjects to be initially enrolled early in the design phase of the study, and with enrollment ongoing throughout the study to continue development.)
• No known neurologic, psychiatric or developmental disability.
• Fluent in spoken and written English

Exclusion criteria:

• Allergy to electrode gel, surgical tape, and metals.
• Subjects under treatment for infectious diseases will be excluded from the study.
• Women who are pregnant or planning to become pregnant during the course of the study will be excluded.
• Contraindications for MRI
• Age over 85 years at time of enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Non-Stroke Pilot Group; Robotic therapy. Aerobic therapy. Subjects without stroke, pilot subjects tested during early phases while the device and therapeutic task specifications are developed, and throughout the project while the device and tasks are refined.	Device: Robotic therapy; The "Robotic" group will use a robotic training protocol to incentivize recovery of motor control by changing task demands throughout the training period. One or more target tasks will be chosen to mimic different sub-functions of gait, including some which are not normally excited in typical cycling behavior. Also, tasks may be designed to target non-gait motions such as hip ab/adduction. The required task may be changed periodically. This therapy protocol will occupy 30 minutes of each training session. Prior to testing, EMG electrodes will be placed on the major muscles of both legs, a procedure that takes roughly 15 minutes. Another 15 minutes is for changing clothes, briefing the subject, and other ancillary study activities. The total time per training session is 1 hour.; Device: Aerobic therapy; The Control group protocol is identical to that of the Robotic group, except the robotically-incentivized exercise is replaced with an aerobic exercise. This intervention emulates a commercial motorized exercise bike to improve cardiovascular unfitness contributions to gait impairment. This therapy implements assist-as-needed and constant-velocity control. The patient's target pedaling speed (e.g. 20 rev/min (to be finalized through pilot tests) and power level (set by heart rate to require approximately 50-70% of maximal oxygen uptake) are set at the beginning of each session and a motor provides assistance or resistance to compensate for the performance of the patient. The exercise will be performed in this mode for 30 minutes per training session.
Other: Non-Stroke Comparison Group; Robotic therapy. Healthy controls enrolled (age 50-85) to contribute to a normative data set on motor learning using the robotic protocols designed for stroke.	Device: Robotic therapy; The "Robotic" group will use a robotic training protocol to incentivize recovery of motor control by changing task demands throughout the training period. One or more target tasks will be chosen to mimic different sub-functions of gait, including some which are not normally excited in typical cycling behavior. Also, tasks may be designed to target non-gait motions such as hip ab/adduction. The required task may be changed periodically. This therapy protocol will occupy 30 minutes of each training session. Prior to testing, EMG electrodes will be placed on the major muscles of both legs, a procedure that takes roughly 15 minutes. Another 15 minutes is for changing clothes, briefing the subject, and other ancillary study activities. The total time per training session is 1 hour.
Experimental: Robotic Training Group; Robotic therapy. Subjects with Stroke who will perform the targeted training task: exercise using novel tasks on a robotic recumbent cycle.	Device: Robotic therapy; The "Robotic" group will use a robotic training protocol to incentivize recovery of motor control by changing task demands throughout the training period. One or more target tasks will be chosen to mimic different sub-functions of gait, including some which are not normally excited in typical cycling behavior. Also, tasks may be designed to target non-gait motions such as hip ab/adduction. The required task may be changed periodically. This therapy protocol will occupy 30 minutes of each training session. Prior to testing, EMG electrodes will be placed on the major muscles of both legs, a procedure that takes roughly 15 minutes. Another 15 minutes is for changing clothes, briefing the subject, and other ancillary study activities. The total time per training session is 1 hour.
Active Comparator: Aerobic Training Group; Aerobic therapy. Subjects with Stroke who will perform aerobic pedaling, duration-matched to the Robotic group.	Device: Aerobic therapy; The Control group protocol is identical to that of the Robotic group, except the robotically-incentivized exercise is replaced with an aerobic exercise. This intervention emulates a commercial motorized exercise bike to improve cardiovascular unfitness contributions to gait impairment. This therapy implements assist-as-needed and constant-velocity control. The patient's target pedaling speed (e.g. 20 rev/min (to be finalized through pilot tests) and power level (set by heart rate to require approximately 50-70% of maximal oxygen uptake) are set at the beginning of each session and a motor provides assistance or resistance to compensate for the performance of the patient. The exercise will be performed in this mode for 30 minutes per training session.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Six Minute Walk Test (6MWT) Distance	A simple series of laps along a 30 m straight path in a level hallway.	Baseline and at 5 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Timed Up-and-Go Test (TUG)	A simple timed test of how long it takes to stand up, walk 10 feet, turn around, return to the starting point, and sit down.	Baseline and at 5 weeks
Change in Self-Selected Walking Speed (SSWS)	A simple test of the speed a person chooses to walk over a 5-meter distance	Baseline and at 5 weeks
Change in Fastest Comfortable Walking Speed (FCWS)	A similar test of the "fastest comfortable speed" a person can use to walk over the 5-meter distance	Baseline and at 5 weeks
Change in Center of Pressure (COP) Characteristics	Movement of the Center of Pressure during standing, with eyes open and eyes closed. With eyes open, subjects focus their eyes on a spot on the wall in front of them. Metrics of COP control include excursion, average velocity, standard deviation, and an estimate of center of mass location.	Baseline and at 5 weeks
Change in Brain Activity in and Near Affected Areas, Through Functional MRI (fMRI)	fMRI scans will be used to measure task-specific cortical activity in sensorimotor areas during physical stepping with an MRI-compatible stepping machine, or imagined/visualized cycling.	Baseline and at 5 weeks

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: National Center for Advancing Translational Sciences (NCATS)
• Investigators: Principal Investigator: Peter G Adamczyk, Ph.D., University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2019
• Primary Completion (Actual): June 29, 2022
• Study Completion (Actual): June 29, 2022

Study Registration Dates

• First Submitted: June 12, 2017
• First Submitted That Met QC Criteria: September 27, 2017
• First Posted (Actual): October 3, 2017

Study Record Updates

• Last Update Posted (Actual): October 5, 2023
• Last Update Submitted That Met QC Criteria: October 3, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 2016-1279; 4UL1TR000427-10 (U.S. NIH Grant/Contract); A196200 (Other Identifier: UW Madison); ENGR\MECHANICAL ENGR (Other Identifier: UW Madison); Protocol Version 1.8, 3/2017 (Other Identifier: UW Madison)

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