Stroke
Conditions
Brief summary
This study will test the hypothesis that the combination of low-moderate to severe motor deficits in the paretic arm and persistent motor deficits in the less-impaired arm limits functional independence in chronic stroke survivors. We, therefore, predict that intense remediation, focused on improving the speed, coordination, and accuracy of the less-impaired arm should improve functional independence.
Detailed description
We previously characterized hemisphere-specific motor control deficits in the non-paretic arm of unilaterally lesioned stroke survivors. Our preliminary data indicate these deficits are substantial and functionally limiting in patients with severe paresis. We have specifically designed an intervention to remediate the hemisphere-specific deficits in the less-impaired arm, using a virtual-reality platform, and then follow this training with manipulation training of a variety of real objects, designed to facilitate generalization and transfer to functional behaviors encountered in the natural environment. We propose a 2-site, two-group randomized intervention with a treatment group, which will receive unilateral training of the less-impaired arm, through our Virtual Reality and Manipulation Training (VRMT) protocol. This intervention protocol is grounded in the premise that targeted remediation of fundamental control deficits exhibited by the less-impaired arm will generalize and transfer beyond practiced tasks to performance of activities of daily living (ADL). This approach contrasts with the more pragmatic approach of task-specific training of essential ADL's, which is limited in scope, more cumbersome, and ignores known fundamental motor control deficits. Our control group will receive conventional intervention, guided by recently released practice guidelines for upper limb intervention in adult stroke. The impact of the proposed research is that we address persistent functional performance deficits in chronic stroke patients with severe paresis, who's less-impaired arm impairments are generally ignored in most current rehabilitation protocols. Our first aim addresses the overall effectiveness of this intervention, relative to our control group: To determine whether non-paretic arm VRMT in chronic stroke survivors with severe paresis will produce durable improvements in less-impaired arm motor performance that will generalize to improve functional activities and functional independence to a greater extent than conventional therapy focused on the paretic arm. Our second aim focuses on the mechanistic basis of potential training-related improvements in motor performance: To determine whether intervention-induced improvements in less-impaired arm performance are associated with improvements in hemisphere-specific reaching kinematics. Finally, our third aim monitors for potential negative effects of our experimental intervention on paretic arm impairment.
Interventions
BEHAVIORALLess-Impaired Arm Training
Participants receive virtual reality and manipulation training in their less impaired arm.
BEHAVIORALContralesional Arm Comparison
Participants receive therapy in their paretic arm, based on the best-practices framework for arm recovery post stroke.
Sponsors
University of Southern California
Penn State University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Robert L. Sainburg
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The outcome assessor will assess all participants and be unaware of the participants' group assignment.
Intervention model description
Participants are randomly assigned to one of two groups. One group (treatment group) receives remediation therapy of the less impaired arm while the control group receives paretic arm therapy.
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. neuroradiological confirmation of unilateral brain damage with residual contralesional upper-extremity weakness 2. deficits in ipsilesional arm performance assessed by the JTHFT 3. 6+ months post stroke 4. Demonstrates cognitive abilities
Exclusion criteria
a history of: 1. neurological disease other than stroke (e.g., head trauma) 2. a major psychiatric diagnosis (e.g., schizophrenia, major affective disorder), 3. hospital admission for substance abuse 4. peripheral disorders affecting sensation or movement of the upper extremities, including pain or arthritis 5. currently taking prescription drugs with known sedative properties that are interfering with sensory-motor function 6. significant joint pain that is activity limiting 7. bilateral stroke
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Jebsen-Taylor Hand Function Test (JTHFT) Times From Baseline 2 to Post Test 1 | Baseline 2 to Post Test 1 (up to 2 weeks post last treatment session) | Measure of unimanual arm performance in a wide range of hand functions required for activities of daily living. The test includes 7 timed (seconds) activities (possible 0-120 seconds each); the analysis excludes the writing component, therefore it includes 6 of the 7 original JTHFT components. Faster performance yields lower scores (time). There were 2 baseline tests (3 weeks apart) to show unchanged performance in assessments prior to training. Training included 15 sessions over the course of up to 7 weeks. Results reported used the second baseline score as the starting value and do not include the first baseline scores. |
| Change in Abilhand Scores From Baseline 2 (Prior to Treatment) to Post Test 1 | Baseline 2 to Post Test 1 (up to 2 weeks post last treatment session) | Participant reported outcome of difficulty of upper extremity based activities. Scores are transformed to logit scores. The items ranged on the interval scale from -2.18 to 1.72 log-odds units, called 'logits', with higher logit values indicating more difficult activities. Deltas of logits from baseline 2 to post test 1 are reported. There were two baseline assessments (3 weeks apart) to show unchanged performance in assessments prior to training. Training included 15 sessions over the course of up to 7 weeks. Results reported used the second baseline score (when participants were randomized) as the starting value and do not include the first baseline scores. Results do not include covariates. |
| Change of Score on Barthel Index From Baseline 2 (Prior to Training) to Post Test 1 | Baseline 2 to Post Test 1 (up to 2 weeks post last treatment session) | Measure of functional independence in self care activities scored from 0-100 with higher scores indicating more functional independence. There were two baseline assessments (3 weeks apart) to show unchanged performance in assessments prior to training. Training included 15 sessions over the course of up to 7 weeks. Results reported used the second baseline score (when participants were randomized) as the starting value and do not include the first baseline scores. |
| Change in Upper-Extremity Fugl-Meyer Assessment (FM) Score From Baseline 2 (Prior to Training) to Post Test 1 | Baseline 2 to Post Test 1 (up to 2 weeks post last treatment session) | Upper-Extremity Measure of paretic arm impairment out of 66 possible points with higher scores indicating more movement, and 0 indicating no functional movement in the arm. There were two baseline assessments (3 weeks apart) to show unchanged performance in assessments prior to training. Training included 15 sessions over the course of up to 7 weeks. Results reported used the second baseline score (when participants were randomized) as the starting value and do not include the first baseline scores. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline 2 (Prior to Training) to Post Test 1 on Contralesional Work Space Area (Kinematics) | Baseline 2 to Post Test 1 (up to 2 weeks post last treatment session) | Workspace area is a kinematic measure of active range of motion, which we measured on the paretic (contralesional) arm. This was calculated by computing the area of the ellipse (measured in centimeters) formed by the major and minor axis of the contralesional arm trajectory on each trial. The major axis was defined as the largest distance between any two points in the handpath, while the minor axis was defined as the largest distance, perpendicular to the major axis. Values were averaged within subjects over all trials for each evaluation (i.e. BL2 and PT1), then group and evaluation averages and standard deviations were calculated from these values. There were two baseline tests (3 weeks apart) to show unchanged performance in assessments prior to training. Training included 15 sessions over the course of up to 7 weeks. Results reported used the second baseline score as the starting value and do not include the first baseline scores. These values do not include covariates. |
| Change in Kinematics- Positional Variability at Maximum Velocity From Baseline 2 (Prior to Training) to Post Test 1 | Baseline 2 to Post Test 1 (up to 2 weeks post last treatment session) | Positional variability is a measure of kinematic variability in reaching movement. This was measured at the participants max reaching velocity and their end position. This was calculated by taking the distance (cm) from the fingertips location at peak velocity/end position on a given trial from its mean location at peak velocity/end position across all trials, for each target. Values were averaged within subjects over all trials for each evaluation (i.e. BL2 and PT1), then group and evaluation averages and standard deviations were calculated from these values. There were two baseline tests (3 weeks apart) to show unchanged performance in assessments prior to training. Training included 15 sessions over the course of up to 7 weeks. Results reported used the second baseline score as the starting value and do not include the first baseline scores or covariates. |
| Change From Baseline 2 (Prior to Training) to Post Test 1on Functional Independence Measure (FIM) -Self Care Components | Baseline 2 to Post Test 1 (up to 2 weeks post last treatment session) | Each item on the FIM is scored on a 7-point Likert scale, and the score indicates the amount of assistance required to perform each item (1 = total assistance in all areas, 7 = total independence in all areas). Analysis includes 6 sub-components of the FIM, which are the self care components (Eating, Grooming, Bathing, Dressing upper body, Dressing lower body, and toileting) (possible 42 points). Higher scores indicate more independence. There were two baseline tests (3 weeks apart) to show unchanged performance in assessments prior to training. Training included 15 sessions over the course of up to 7 weeks. Results reported used the second baseline score as the starting value and do not include the first baseline scores. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ipsilesional Arm Training (Experimental Condition) Intervention condition includes therapy of the less-impaired ipsilesional arm.
Ipsilesional Arm Training: Participants receive virtual reality and manipulation training in their less impaired arm. | 29 |
| Contralesional Arm (Comparison Condition) Comparison control condition includes therapy of the paretic (contralesional) arm.
Contralesional Arm Comparison: Participants receive therapy in their paretic arm, based on the best-practices framework for arm recovery post stroke. | 29 |
| Total | 58 |
Baseline characteristics
| Characteristic | Ipsilesional Arm Training (Experimental Condition) | Contralesional Arm (Comparison Condition) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 9 Participants | 17 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants | 20 Participants | 41 Participants |
| Age, Continuous | 58 years | 59 years | 59 years |
| Jebsen-Taylor Hand Function Test | 29 Participants | 29 Participants | 58 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 23 Participants | 23 Participants | 46 Participants |
| Region of Enrollment United States | 29 participants | 29 participants | 58 participants |
| Sex: Female, Male Female | 9 Participants | 9 Participants | 18 Participants |
| Sex: Female, Male Male | 20 Participants | 20 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 29 |
| other Total, other adverse events | 2 / 29 | 4 / 29 |
| serious Total, serious adverse events | 2 / 29 | 1 / 29 |
Outcome results
Primary
Change in Abilhand Scores From Baseline 2 (Prior to Treatment) to Post Test 1
Participant reported outcome of difficulty of upper extremity based activities. Scores are transformed to logit scores. The items ranged on the interval scale from -2.18 to 1.72 log-odds units, called 'logits', with higher logit values indicating more difficult activities. Deltas of logits from baseline 2 to post test 1 are reported. There were two baseline assessments (3 weeks apart) to show unchanged performance in assessments prior to training. Training included 15 sessions over the course of up to 7 weeks. Results reported used the second baseline score (when participants were randomized) as the starting value and do not include the first baseline scores. Results do not include covariates.
Time frame: Baseline 2 to Post Test 1 (up to 2 weeks post last treatment session)
Population: All participants with baseline 2 and post test 1 data were included in analysis. Scores are transformed to logit scores. The items ranged on the interval scale from -2.18 to 1.72 log-odds units, called 'logits', with higher logit values indicating more difficult activities. Deltas of logits from baseline 2 to post test 1 are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ipsilesional Arm Training (Experimental Condition) | Change in Abilhand Scores From Baseline 2 (Prior to Treatment) to Post Test 1 | -2.08 score on a scale | Standard Error 1.43 |
| Contralesional Arm (Comparison Condition) | Change in Abilhand Scores From Baseline 2 (Prior to Treatment) to Post Test 1 | -.57 score on a scale | Standard Error 1.18 |
Primary
Change in Jebsen-Taylor Hand Function Test (JTHFT) Times From Baseline 2 to Post Test 1
Measure of unimanual arm performance in a wide range of hand functions required for activities of daily living. The test includes 7 timed (seconds) activities (possible 0-120 seconds each); the analysis excludes the writing component, therefore it includes 6 of the 7 original JTHFT components. Faster performance yields lower scores (time). There were 2 baseline tests (3 weeks apart) to show unchanged performance in assessments prior to training. Training included 15 sessions over the course of up to 7 weeks. Results reported used the second baseline score as the starting value and do not include the first baseline scores.
Time frame: Baseline 2 to Post Test 1 (up to 2 weeks post last treatment session)
Population: 5 participants were randomized, but did not complete intervention due to Covid epidemic, and thus did not have JTHFT at post test 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ipsilesional Arm Training (Experimental Condition) | Change in Jebsen-Taylor Hand Function Test (JTHFT) Times From Baseline 2 to Post Test 1 | 5.07 seconds | Standard Error 0.93 |
| Contralesional Arm (Comparison Condition) | Change in Jebsen-Taylor Hand Function Test (JTHFT) Times From Baseline 2 to Post Test 1 | -.11 seconds | Standard Error 1.37 |
p-value: <0.0595% CI: [2.31, 9.14]Regression, Linear
Primary
Change in Upper-Extremity Fugl-Meyer Assessment (FM) Score From Baseline 2 (Prior to Training) to Post Test 1
Upper-Extremity Measure of paretic arm impairment out of 66 possible points with higher scores indicating more movement, and 0 indicating no functional movement in the arm. There were two baseline assessments (3 weeks apart) to show unchanged performance in assessments prior to training. Training included 15 sessions over the course of up to 7 weeks. Results reported used the second baseline score (when participants were randomized) as the starting value and do not include the first baseline scores.
Time frame: Baseline 2 to Post Test 1 (up to 2 weeks post last treatment session)
Population: Only participants with data at baseline 2 and post test 1 are included in analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ipsilesional Arm Training (Experimental Condition) | Change in Upper-Extremity Fugl-Meyer Assessment (FM) Score From Baseline 2 (Prior to Training) to Post Test 1 | -.68 score on a scale | Standard Error 0.8 |
| Contralesional Arm (Comparison Condition) | Change in Upper-Extremity Fugl-Meyer Assessment (FM) Score From Baseline 2 (Prior to Training) to Post Test 1 | -1.61 score on a scale | Standard Error 0.93 |
p-value: <0.0595% CI: [-2.29, 4.53]Regression, Linear
Primary
Change of Score on Barthel Index From Baseline 2 (Prior to Training) to Post Test 1
Measure of functional independence in self care activities scored from 0-100 with higher scores indicating more functional independence. There were two baseline assessments (3 weeks apart) to show unchanged performance in assessments prior to training. Training included 15 sessions over the course of up to 7 weeks. Results reported used the second baseline score (when participants were randomized) as the starting value and do not include the first baseline scores.
Time frame: Baseline 2 to Post Test 1 (up to 2 weeks post last treatment session)
Population: Only participants with baseline 2 and post test 1 are included in analysis. Delta values from baseline 2 to post test 1 are reported and adjusted for age, sex, and hemisphere of lesion.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ipsilesional Arm Training (Experimental Condition) | Change of Score on Barthel Index From Baseline 2 (Prior to Training) to Post Test 1 | -1.2 score on a scale | Standard Error 1.83 |
| Contralesional Arm (Comparison Condition) | Change of Score on Barthel Index From Baseline 2 (Prior to Training) to Post Test 1 | -1.79 score on a scale | Standard Error 1.24 |
p-value: <0.0595% CI: [-2.58, 4.24]Regression, Linear
Secondary
Change From Baseline 2 (Prior to Training) to Post Test 1 on Contralesional Work Space Area (Kinematics)
Workspace area is a kinematic measure of active range of motion, which we measured on the paretic (contralesional) arm. This was calculated by computing the area of the ellipse (measured in centimeters) formed by the major and minor axis of the contralesional arm trajectory on each trial. The major axis was defined as the largest distance between any two points in the handpath, while the minor axis was defined as the largest distance, perpendicular to the major axis. Values were averaged within subjects over all trials for each evaluation (i.e. BL2 and PT1), then group and evaluation averages and standard deviations were calculated from these values. There were two baseline tests (3 weeks apart) to show unchanged performance in assessments prior to training. Training included 15 sessions over the course of up to 7 weeks. Results reported used the second baseline score as the starting value and do not include the first baseline scores. These values do not include covariates.
Time frame: Baseline 2 to Post Test 1 (up to 2 weeks post last treatment session)
Population: Participants were excluded from this analysis if they could not complete the kinematics for any reason (i.e.: Covid, a pacemaker, not fitting in the kinematic setup), or did not complete both baseline and post test 1 kinematic assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ipsilesional Arm Training (Experimental Condition) | Change From Baseline 2 (Prior to Training) to Post Test 1 on Contralesional Work Space Area (Kinematics) | 0.512 centimeters | Standard Deviation 2.1217 |
| Contralesional Arm (Comparison Condition) | Change From Baseline 2 (Prior to Training) to Post Test 1 on Contralesional Work Space Area (Kinematics) | 0.340 centimeters | Standard Deviation 1.6714 |
Secondary
Change From Baseline 2 (Prior to Training) to Post Test 1on Functional Independence Measure (FIM) -Self Care Components
Each item on the FIM is scored on a 7-point Likert scale, and the score indicates the amount of assistance required to perform each item (1 = total assistance in all areas, 7 = total independence in all areas). Analysis includes 6 sub-components of the FIM, which are the self care components (Eating, Grooming, Bathing, Dressing upper body, Dressing lower body, and toileting) (possible 42 points). Higher scores indicate more independence. There were two baseline tests (3 weeks apart) to show unchanged performance in assessments prior to training. Training included 15 sessions over the course of up to 7 weeks. Results reported used the second baseline score as the starting value and do not include the first baseline scores.
Time frame: Baseline 2 to Post Test 1 (up to 2 weeks post last treatment session)
Population: All participants with baseline 2 and post test 1 data were analyzed (N=53). 5 randomized participants were excluded from analysis because they did not have baseline 2 and post test 1 measures due to Covid disruption.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ipsilesional Arm Training (Experimental Condition) | Change From Baseline 2 (Prior to Training) to Post Test 1on Functional Independence Measure (FIM) -Self Care Components | -1.44 score on a scale | Standard Error 0.75 |
| Contralesional Arm (Comparison Condition) | Change From Baseline 2 (Prior to Training) to Post Test 1on Functional Independence Measure (FIM) -Self Care Components | -.46 score on a scale | Standard Error 0.81 |
Secondary
Change in Kinematics- Positional Variability at Maximum Velocity From Baseline 2 (Prior to Training) to Post Test 1
Positional variability is a measure of kinematic variability in reaching movement. This was measured at the participants max reaching velocity and their end position. This was calculated by taking the distance (cm) from the fingertips location at peak velocity/end position on a given trial from its mean location at peak velocity/end position across all trials, for each target. Values were averaged within subjects over all trials for each evaluation (i.e. BL2 and PT1), then group and evaluation averages and standard deviations were calculated from these values. There were two baseline tests (3 weeks apart) to show unchanged performance in assessments prior to training. Training included 15 sessions over the course of up to 7 weeks. Results reported used the second baseline score as the starting value and do not include the first baseline scores or covariates.
Time frame: Baseline 2 to Post Test 1 (up to 2 weeks post last treatment session)
Population: Participants were excluded if they could not complete the kinematic portion of the study due to Covid, or a pacemaker, or not fitting in the kinematic setup, or if they didn't complete both baseline and post test 1 assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ipsilesional Arm Training (Experimental Condition) | Change in Kinematics- Positional Variability at Maximum Velocity From Baseline 2 (Prior to Training) to Post Test 1 | Maximum Velocity | 0.0930727 Centimeters | Standard Deviation 0.4369149 |
| Ipsilesional Arm Training (Experimental Condition) | Change in Kinematics- Positional Variability at Maximum Velocity From Baseline 2 (Prior to Training) to Post Test 1 | End Position | 0.2811583 Centimeters | Standard Deviation 0.5066384 |
| Contralesional Arm (Comparison Condition) | Change in Kinematics- Positional Variability at Maximum Velocity From Baseline 2 (Prior to Training) to Post Test 1 | Maximum Velocity | -0.0225708 Centimeters | Standard Deviation 0.4979299 |
| Contralesional Arm (Comparison Condition) | Change in Kinematics- Positional Variability at Maximum Velocity From Baseline 2 (Prior to Training) to Post Test 1 | End Position | -0.1156399 Centimeters | Standard Deviation 1.1076122 |