Stroke
Conditions
Keywords
arm rehabilitation, recovery of function
Brief summary
The purpose of this study is to design a predictive model of stroke recovery based on baseline measurements of arm movement and brain physiology. The expectation is the development of a formula to predict a person's response to an arm rehabilitation program provided in the chronic phase (6 months or greater post stroke) of recovery. The study will include magnetic resonance imaging (MRI), transcranial magnetic stimulation (TMS), genetic testing using blood and saliva, and an arm exercise program consisting of robot-assisted exercise combined with functional arm exercise called transition to task training (TTT).
Detailed description
After informed consent, a baseline neurological exam, medical records review, MRI of the brain, TMS, questionnaires, cognitive testing, robot evaluations, and arm function testing will occur. Baseline testing will occur in the first 4-6 weeks of participation including two separate sessions approximately 1 week a part to examine arm strength, range of motion, and ability to perform functional tasks, with one additional session if needed to verify stability between results. Additionally, one robot evaluation, one MRI, and one TMS session will be completed. We will also collect genetic data using blood and saliva samples to examine potential RNA expression and genetic polymorphisms that might influence response to therapy. The intervention phase consists of 12 weeks of robot and transition to task arm exercise training (TTT). Interventions will occur approximately 3 times per week for 12 weeks for a total of 36 visits. Additional time and visits will be allowed with visits occurring 4 times per week or up to 6 additional weeks (not to exceed 18 weeks) if scheduling conflicts arise. The intervention sessions will be one hour in duration. During the hour-long intervention, 45 minutes of robotic intervention will be followed by 15 minutes of TTT. Two separate robots targeting different movements will be used for the 3 phases of the robot training. The training will be sequential with 12 sessions completed on the wrist robot, followed by 12 sessions on the shoulder-elbow robot and the final 12 sessions alternating between the wrist and elbow-shoulder robot. After the final training session, subjects will return after a 12 week retention period. At various time points during and after the intervention phase there will be additional arm function testing, robot evaluations, questionnaires, blood draws, and TMS sessions to re-assess ability.
Interventions
DEVICERobot + TTT exercise
The intervention will be completed 36 visits approximately 3x/week for 12-18 weeks. The training progression will be sequential with 12 visits completed on the wrist robot, followed by 12 visits on the shoulder-elbow robot and completing with 12 visits alternating sessions on the wrist and shoulder-elbow robot. Participants will perform robot training for 45 minutes with each robot followed by 15 minutes of TTT practice to complete their 60 minute intervention session.
Sponsors
VA Maryland Health Care System
VA Office of Research and Development
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
The outcomes assessor is masked as to the prediction model and to particulars of performance during the intervention, but knows that there is a single group design.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinically defined, unilateral, hemiparetic stroke with radiologic exclusion of other possible diagnosis * Stroke onset at least 6 months before enrollment * Present with Mild/Moderate to Severe arm dysfunction (based on Fugl-Meyer scores of 10 to 45) * Be medically stable to participate in the study and not have contractures or other impairments that would interfere with the interventional training.
Exclusion criteria
* Unable to give informed consent * Have a serious complicating medical illness that would preclude participation. * Contractures or orthopedic problems limiting range of joint motion in the potential study arm * Visual loss such that the subject would not be able to see the test patterns on the robot computer monitor * Botulinum toxin to study arm within four months of study enrollment or if received during the study period * Unable to comply with requirements of the study * Participants with a history of a seizure will not be precluded from the study, but will not be enrolled in the TMS portions * Participants with electromagnetic exclusions (metal implants in the cranium, implanted electronic devices etc.) will not be precluded from the study but will be excluded from the MRI and TMS portions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stroke Impact Scale: Hand | Baseline, after visit 36, and 12 week retention | The Stroke Impact Scale (SIS) is one of the primary outcome measures assessing change in hand use from baseline testing to mid-training after visits 12 and 24, and post-training after visit 36 and the 12 week retention period. It is a self-report structured interview consisting of eight domains designed to assess physical, mental and emotional changes following stroke that contribute to quality of life. It has been tested and found to be reliable, valid, and sensitive to change in the stroke population. It has four physical domain subscales that can be analyzed separately. The SIS hand subscale will be the focus for our outcome measure. Higher scores indicate greater function and life satisfaction. The minimum and maximum for the subscale is 0 and 100 respectively. |
| Fugl-Meyer Upper Extremity Assessment | Baseline, after visits 12, 24, and 36, and 12 week retention | The Fugl-Meyer is one of the primary outcome measures assessing change in arm use from baseline testing to mid-training after visits 12 and 24, and post-training after visit 36 and the 12 week retention period. It is a stroke-specific measure of impairment of the upper extremity that has been shown to be valid and reliable with high inter-rater and test-retest reliability. It provides a direct-observational assessment of volitional movement and motor impairment related to reflexes, sensation, and abnormal synergies. Each item on the FM is rated on a three-point ordinal scale (0 = cannot perform, 1 = performs partially, 2 = performs fully). The scale ranges from 0-66 with higher scores representing less motor impairment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Action Research Arm Test (ARAT) | Baseline, after visits 12, 24, and 36, and 12 week retention | The ARAT will be used to assess change from baseline testing to mid-training after visits 12 and 24, and post-training after visit 36 and the 12 week retention period. It is a stroke-specific measure of arm motor function and impairment of the upper extremity that has been shown to be valid and reliable with high inter-rater and test-retest reliability. It provides a direct-observational assessment of volitional movement. It includes 19 test activities and each test is given an ordinal score of 0, 1, 2, or 3, with higher values indicating better arm motor status. The total ARAT score is the sum of the 19 tests, and thus the maximum score is 57. |
| 6-Item Wolf Motor Function Test (WMFT) | Baseline, after visits 12, 24, and 36, and 12 week retention | The Streamlined 6-Item Wolf Motor Function Test (WMFT) will be used to assess change from baseline testing to mid-training after visits 12 and 24, and post-training after visit 36 and the 12 week retention period. It examines UE function based on task performance time, and quality of movement. Functional use and speed of movement are based on six timed activities. It has been examined in chronic stroke and has high inter-rater reliability, internal consistency, and test-retest reliability. Timed tasks that cannot be completed default to a time score of 120 seconds. Faster times or a lower score in seconds represent better function. The maximum score of 75 (minimum score 0) refers to perfect score on the full 15 item functional ability assessment (15 x 5.) |
Other
| Measure | Time frame | Description |
|---|---|---|
| TMS Score: Three Muscle Responses to Transcranial Magnetic Stimulation of the Motor Cortex | Baseline, after visit 36, and 12 week retention | TMS stimulation of the motor cortex will be performed using MagStim 200 Magnetic Stimulators (MagStim Ltd., Wales, UK) at baseline and post training after visit 36 and the 12 week retention to assess change in the motor evoked potential (MEP) of the arm muscles. TMS testing is as follows: 1) Location of muscle hotspot (highest motor evoked potential), 2) Threshold (lowest stimulation strength that evokes an MEP at hotspot) 3) Ipsilateral silent period measured on both the affected and unaffected side. A score on the scale of 0-9, 9 indicating a greater nervous system response. |
Countries
United States
Participant flow
Recruitment details
There were 68 participants consented. Of these 46 were eligible and entered the intervention. Four did not complete due to transportation issues, scheduling conflicts or lack of communication.
Participants by arm
| Arm | Count |
|---|---|
| Device: Robot + TTT Exercise All participants will be enrolled in this group to receive the same 60 minute study intervention consisting of wrist and shoulder-elbow robot training and TTT arm exercises.
Robot + TTT exercise: The intervention will be completed 36 visits approximately 3x/week for 12-18 weeks. The training progression will be sequential with 12 visits completed on the wrist robot, followed by 12 visits on the shoulder-elbow robot and completing with 12 visits alternating sessions on the wrist and shoulder-elbow robot. Participants will perform robot training for 45 minutes with each robot followed by 15 minutes of TTT practice to complete their 60 minute intervention session. | 42 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Device: Robot + TTT Exercise |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 15 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants |
| Age, Continuous | 59.80952381 years STANDARD_DEVIATION 11.2818397 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 42 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 23 Participants |
| Race (NIH/OMB) More than one race | 0 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 | 19 Participants |
| Region of Enrollment United States | 42 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 42 |
| other Total, other adverse events | 0 / 42 |
| serious Total, serious adverse events | 0 / 42 |
Outcome results
Primary
Fugl-Meyer Upper Extremity Assessment
The Fugl-Meyer is one of the primary outcome measures assessing change in arm use from baseline testing to mid-training after visits 12 and 24, and post-training after visit 36 and the 12 week retention period. It is a stroke-specific measure of impairment of the upper extremity that has been shown to be valid and reliable with high inter-rater and test-retest reliability. It provides a direct-observational assessment of volitional movement and motor impairment related to reflexes, sensation, and abnormal synergies. Each item on the FM is rated on a three-point ordinal scale (0 = cannot perform, 1 = performs partially, 2 = performs fully). The scale ranges from 0-66 with higher scores representing less motor impairment.
Time frame: Baseline, after visits 12, 24, and 36, and 12 week retention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Device: Robot + TTT Exercise | Fugl-Meyer Upper Extremity Assessment | Baseline | 19.8 score on a scale | Standard Deviation 9.62 |
| Device: Robot + TTT Exercise | Fugl-Meyer Upper Extremity Assessment | After visit 12 | 22.2 score on a scale | Standard Deviation 11.23 |
| Device: Robot + TTT Exercise | Fugl-Meyer Upper Extremity Assessment | After visit 24 | 24.0 score on a scale | Standard Deviation 13.08 |
| Device: Robot + TTT Exercise | Fugl-Meyer Upper Extremity Assessment | After visit 36 | 24.4 score on a scale | Standard Deviation 13.15 |
| Device: Robot + TTT Exercise | Fugl-Meyer Upper Extremity Assessment | 12-week retention | 25.2 score on a scale | Standard Deviation 13.36 |
Primary
Stroke Impact Scale: Hand
The Stroke Impact Scale (SIS) is one of the primary outcome measures assessing change in hand use from baseline testing to mid-training after visits 12 and 24, and post-training after visit 36 and the 12 week retention period. It is a self-report structured interview consisting of eight domains designed to assess physical, mental and emotional changes following stroke that contribute to quality of life. It has been tested and found to be reliable, valid, and sensitive to change in the stroke population. It has four physical domain subscales that can be analyzed separately. The SIS hand subscale will be the focus for our outcome measure. Higher scores indicate greater function and life satisfaction. The minimum and maximum for the subscale is 0 and 100 respectively.
Time frame: Baseline, after visit 36, and 12 week retention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Device: Robot + TTT Exercise | Stroke Impact Scale: Hand | 12-week retention visit | 30.0 score on a scale | Standard Deviation 30.57 |
| Device: Robot + TTT Exercise | Stroke Impact Scale: Hand | Baseline | 20.4 score on a scale | Standard Deviation 27.13 |
| Device: Robot + TTT Exercise | Stroke Impact Scale: Hand | After visit 36 | 22.2 score on a scale | Standard Deviation 24.26 |
Secondary
6-Item Wolf Motor Function Test (WMFT)
The Streamlined 6-Item Wolf Motor Function Test (WMFT) will be used to assess change from baseline testing to mid-training after visits 12 and 24, and post-training after visit 36 and the 12 week retention period. It examines UE function based on task performance time, and quality of movement. Functional use and speed of movement are based on six timed activities. It has been examined in chronic stroke and has high inter-rater reliability, internal consistency, and test-retest reliability. Timed tasks that cannot be completed default to a time score of 120 seconds. Faster times or a lower score in seconds represent better function. The maximum score of 75 (minimum score 0) refers to perfect score on the full 15 item functional ability assessment (15 x 5.)
Time frame: Baseline, after visits 12, 24, and 36, and 12 week retention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Device: Robot + TTT Exercise | 6-Item Wolf Motor Function Test (WMFT) | After visit 24 | 1.9 units on a scale | Standard Deviation 1 |
| Device: Robot + TTT Exercise | 6-Item Wolf Motor Function Test (WMFT) | After visit 36 | 2.0 units on a scale | Standard Deviation 1.13 |
| Device: Robot + TTT Exercise | 6-Item Wolf Motor Function Test (WMFT) | 12-week retention | 2.0 units on a scale | Standard Deviation 1.2 |
| Device: Robot + TTT Exercise | 6-Item Wolf Motor Function Test (WMFT) | Baseline | 1.7 units on a scale | Standard Deviation 0.89 |
| Device: Robot + TTT Exercise | 6-Item Wolf Motor Function Test (WMFT) | After visit 12 | 1.8 units on a scale | Standard Deviation 1.08 |
Secondary
Action Research Arm Test (ARAT)
The ARAT will be used to assess change from baseline testing to mid-training after visits 12 and 24, and post-training after visit 36 and the 12 week retention period. It is a stroke-specific measure of arm motor function and impairment of the upper extremity that has been shown to be valid and reliable with high inter-rater and test-retest reliability. It provides a direct-observational assessment of volitional movement. It includes 19 test activities and each test is given an ordinal score of 0, 1, 2, or 3, with higher values indicating better arm motor status. The total ARAT score is the sum of the 19 tests, and thus the maximum score is 57.
Time frame: Baseline, after visits 12, 24, and 36, and 12 week retention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Device: Robot + TTT Exercise | Action Research Arm Test (ARAT) | Baseline | 14.4 score on a scale | Standard Deviation 14.67 |
| Device: Robot + TTT Exercise | Action Research Arm Test (ARAT) | After visit 12 | 14.9 score on a scale | Standard Deviation 15.33 |
| Device: Robot + TTT Exercise | Action Research Arm Test (ARAT) | After visit 24 | 16.2 score on a scale | Standard Deviation 16.82 |
| Device: Robot + TTT Exercise | Action Research Arm Test (ARAT) | After visit 36 | 16.4 score on a scale | Standard Deviation 16.57 |
| Device: Robot + TTT Exercise | Action Research Arm Test (ARAT) | 12-week retention | 16.8 score on a scale | Standard Deviation 17.73 |
Other Pre-specified
TMS Score: Three Muscle Responses to Transcranial Magnetic Stimulation of the Motor Cortex
TMS stimulation of the motor cortex will be performed using MagStim 200 Magnetic Stimulators (MagStim Ltd., Wales, UK) at baseline and post training after visit 36 and the 12 week retention to assess change in the motor evoked potential (MEP) of the arm muscles. TMS testing is as follows: 1) Location of muscle hotspot (highest motor evoked potential), 2) Threshold (lowest stimulation strength that evokes an MEP at hotspot) 3) Ipsilateral silent period measured on both the affected and unaffected side. A score on the scale of 0-9, 9 indicating a greater nervous system response.
Time frame: Baseline, after visit 36, and 12 week retention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Device: Robot + TTT Exercise | TMS Score: Three Muscle Responses to Transcranial Magnetic Stimulation of the Motor Cortex | Baseline | 2.4 score on a scale | Standard Deviation 2.8 |
| Device: Robot + TTT Exercise | TMS Score: Three Muscle Responses to Transcranial Magnetic Stimulation of the Motor Cortex | After visit 36 | 2.6 score on a scale | Standard Deviation 3.03 |
| Device: Robot + TTT Exercise | TMS Score: Three Muscle Responses to Transcranial Magnetic Stimulation of the Motor Cortex | 12-week retention | 2.5 score on a scale | Standard Deviation 3.09 |