Stroke
Conditions
Brief summary
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.
Interventions
DEVICERobotic 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.
DEVICEAerobic 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.
Sponsors
National Center for Advancing Translational Sciences (NCATS)
University of Wisconsin, Madison
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Six Minute Walk Test (6MWT) Distance | Baseline and at 5 weeks | A simple series of laps along a 30 m straight path in a level hallway. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Brain Activity in and Near Affected Areas, Through Functional MRI (fMRI) | Baseline and at 5 weeks | 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. |
| Change in Timed Up-and-Go Test (TUG) | Baseline and at 5 weeks | 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. |
| Change in Self-Selected Walking Speed (SSWS) | Baseline and at 5 weeks | A simple test of the speed a person chooses to walk over a 5-meter distance |
| Change in Fastest Comfortable Walking Speed (FCWS) | Baseline and at 5 weeks | A similar test of the fastest comfortable speed a person can use to walk over the 5-meter distance |
| Change in Center of Pressure (COP) Characteristics | Baseline and at 5 weeks | 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. |
Countries
United States
Participant flow
Recruitment details
Healthy participants were recruited from June 2019 to June 2022.
Pre-assignment details
Original study plan required re-evaluation and the decision was made to pivot to developing tests and exercises on healthy population. A clinical trial was not conducted.
Participants by arm
| Arm | Count |
|---|---|
| Non-Stroke Pilot Group Robotic therapy and 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. | 44 |
| Total | 44 |
Baseline characteristics
| Characteristic | Non-Stroke Pilot Group |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 44 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 11 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 25 Participants |
| Region of Enrollment United States | 44 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 44 |
| other Total, other adverse events | 0 / 44 |
| serious Total, serious adverse events | 0 / 44 |
Outcome results
Primary
Change in Six Minute Walk Test (6MWT) Distance
A simple series of laps along a 30 m straight path in a level hallway.
Time frame: Baseline and at 5 weeks
Population: Healthy Pilot Group participants were enrolled and the study team learned that the protocol was insufficient to test the hypothesis. No data were collected for this measure.
Secondary
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.
Time frame: Baseline and at 5 weeks
Population: Healthy Pilot Group participants were enrolled and the study team learned that the protocol was insufficient to test the hypothesis. No data were collected for this measure.
Secondary
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.
Time frame: Baseline and at 5 weeks
Population: Healthy Pilot Group participants were enrolled and the study team learned that the protocol was insufficient to test the hypothesis. No data were collected for this measure.
Secondary
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
Time frame: Baseline and at 5 weeks
Population: Healthy Pilot Group participants were enrolled and the study team learned that the protocol was insufficient to test the hypothesis. No data were collected for this measure.
Secondary
Change in Self-Selected Walking Speed (SSWS)
A simple test of the speed a person chooses to walk over a 5-meter distance
Time frame: Baseline and at 5 weeks
Population: Healthy Pilot Group participants were enrolled and the study team learned that the protocol was insufficient to test the hypothesis. No data were collected for this measure.
Secondary
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.
Time frame: Baseline and at 5 weeks
Population: Healthy Pilot Group participants were enrolled and the study team learned that the protocol was insufficient to test the hypothesis. No data were collected for this measure.
Post Hoc
Movement Settling Time: Reaching Against a Damper-Like Force
The test involved reaching against viscous damper torque, where the damping constant (units: Nm/(rad/s) = torque produced by the robot per rad/s of crank velocity) was changed by the computer in a structured but unpredictable sequence, across the trials. Movement settling time is defined as time for crank angle to settle between 40 and 50 degrees, when the central target was 45 degrees. Low damping = 3 Nm/(rad/s), High damping = 9 Nm/(rad/s).
Time frame: 1 visit roughly 3 hours
Population: Original study plan required re-evaluation and the decision was made to pivot to developing tests and exercises on healthy population. A clinical trial was not conducted. Summary Data collected from experimental tasks in development are reported here as post-hoc outcomes.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Non-Stroke Pilot Group | Movement Settling Time: Reaching Against a Damper-Like Force | high damping | 1.21 seconds | Standard Deviation 0.04 |
| Non-Stroke Pilot Group | Movement Settling Time: Reaching Against a Damper-Like Force | low damping | 1.17 seconds | Standard Deviation 0.056 |
Post Hoc
Movement Settling Time: Reaching Against a Spring-Like Torque
The test involved reaching against spring-like torque, where the spring stiffness was mostly constant but was changed unexpectedly by the computer in different trials. Movement Settling Time definition: time for crank angle to settle between 40 and 50 degrees, when the central target was 45 degrees. Low stiffness = 10 Nm/rad; Medium stiffness = 20 Nm/rad; High stiffness = 30 Nm/rad Catch trials are unexpected medium stiffness setting, unpredictably spaced.
Time frame: 1 visit roughly 3 hours
Population: Original study plan required re-evaluation and the decision was made to pivot to developing tests and exercises on healthy population. A clinical trial was not conducted. Summary Data collected from experimental tasks in development are reported here as post-hoc outcomes.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Non-Stroke Pilot Group | Movement Settling Time: Reaching Against a Spring-Like Torque | high stiffness training | 1.21 seconds | Standard Deviation 0.068 |
| Non-Stroke Pilot Group | Movement Settling Time: Reaching Against a Spring-Like Torque | low stiffness training | 1.24 seconds | Standard Deviation 0.071 |
| Non-Stroke Pilot Group | Movement Settling Time: Reaching Against a Spring-Like Torque | catch medium trials when training was high | 1.29 seconds | Standard Deviation 0.079 |
| Non-Stroke Pilot Group | Movement Settling Time: Reaching Against a Spring-Like Torque | catch medium trials when training was low | 1.40 seconds | Standard Deviation 0.096 |
Post Hoc
Movement Settling Time With Damping Level Cued Visually
The test involved reaching against viscous damper torque, where the damping constant (units: Nm/(rad/s) = torque produced by the robot per rad/s of crank velocity) was changed by the computer in a structured but unpredictable sequence, across the trials. Movement settling time is defined as time for crank angle to settle between 40 and 50 degrees, when the central target was 45 degrees. In this experiment, the damping level was visually cued. Low damping = 3 Nm/(rad/s), High damping = 9 Nm/(rad/s)
Time frame: 1 visit roughly 3 hours
Population: Original study plan required re-evaluation and the decision was made to pivot to developing tests and exercises on healthy population. A clinical trial was not conducted. Summary Data collected from experimental tasks in development are reported here as post-hoc outcomes.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Non-Stroke Pilot Group | Movement Settling Time With Damping Level Cued Visually | High Damping Cued Visually | 1.16 seconds | Standard Deviation 0.041 |
| Non-Stroke Pilot Group | Movement Settling Time With Damping Level Cued Visually | Low Damping Cued Visually | 1.13 seconds | Standard Deviation 0.03 |
Post Hoc
Number of Participants Who Completed the Half-Reversed Cycling Task
The effect of pushing on one specific pedal was reversed by the computer in its calculation of how to move the crank; the other pedal had a physically typical effect. The task was to cause this complex system to move the crank at a constant 20 RPM forward speed (i.e., minimize the error in speed from this target). Reported here are the number of participants who completed this task.
Time frame: Five training sessions of 45 minutes, each on a different day within roughly one week. Additionally, a 6th session with the effects of the two pedals switched
Population: Original study plan required re-evaluation and the decision was made to pivot to developing tests and exercises on healthy population. A clinical trial was not conducted. Summary Data collected from experimental tasks in development are reported here as post-hoc outcomes.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Non-Stroke Pilot Group | Number of Participants Who Completed the Half-Reversed Cycling Task | 21 Participants |
Post Hoc
Reaction Time in Medium Catch Trials
The test involved reaching against spring-like torque, where the spring stiffness was mostly constant but was changed unexpectedly by the computer in different trials. Reaction time definition: time from a visual and auditory cue to initial movement. Participants were Trained with mostly a Low or High stiffness (each in a separate block of reaches) and had Catch trials when the stiffness was changed to Medium. Low stiffness = 10 Newton meter per radian (Nm/rad); Medium stiffness = 20 Nm/rad; High stiffness = 30 Nm/rad
Time frame: 1 visit roughly 3 hours
Population: Original study plan required re-evaluation and the decision was made to pivot to developing tests and exercises on healthy population. A clinical trial was not conducted. Summary Data collected from experimental tasks in development are reported here as post-hoc outcomes.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Non-Stroke Pilot Group | Reaction Time in Medium Catch Trials | Train High, Catch Medium | 0.366 seconds | Standard Deviation 0.038 |
| Non-Stroke Pilot Group | Reaction Time in Medium Catch Trials | Train Low, Catch Medium | 0.375 seconds | Standard Deviation 0.037 |
Post Hoc
Undershoot and Overshoot in Catch Trials
The test involved reaching against spring-like torque, where the spring stiffness was mostly constant but was changed unexpectedly by the computer in different trials. All participants had a block with Low training, called Train Low Catch Medium, and a separate block with High training, called Train High Catch Medium. Undershoot: initial reach showed undershoot relative to the target crank angle of 45 degrees, with the value measured as the local minimum as the pedal momentarily stopped and went backward. Overshoot: initial reach showed overshoot beyond the target crank angle of 45 degrees, with the value measured as the maximum angle during that period.
Time frame: 1 visit roughly 3 hours
Population: Original study plan required re-evaluation and the decision was made to pivot to developing tests and exercises on healthy population. A clinical trial was not conducted. Summary Data collected from experimental tasks in development are reported here as post-hoc outcomes.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Non-Stroke Pilot Group | Undershoot and Overshoot in Catch Trials | Undershoot | 37.3 degrees | Standard Deviation 2.1 |
| Non-Stroke Pilot Group | Undershoot and Overshoot in Catch Trials | Overshoot | 52.4 degrees | Standard Deviation 2.6 |