Robotic Assisted Upper-Limb Neurorehabilitation in Stroke Patients

Study Overview
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Brief Summary
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This study will compare robotic training with usual care and intensive comparison therapy to attempt to improve upper extremity function.

Detailed Description
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Primary Hypothesis: The primary hypothesis is that robotic training compared with usual care and intensive comparison therapy will lead to improved upper extremity function. Eligible patients will be randomized to one of three treatment arms: 1) usual care, 2) intensive comparison therapy, or 3) robotic training. Participants assigned to intensive comparison therapy or robot-assisted training will receive treatment for 12 weeks consisting of three one-hour sessions a week and then usual care for the remainder of follow-up. Those assigned to usual care will receive the usual stroke care as delivered at each participating medical center for 36 weeks and then will be offered, as compassionate care, their choice of either robot-assisted or intensive comparison therapy. Secondary Hypothesis: The secondary hypotheses are that compared with usual care and intensive comparison therapy, robotic treatment will lead to improved quality of life and task performance involving proximal and distal control of the paretic arm. If the robotic arm is effective, two other secondary objects are to evaluate its early (less than 12 week) and late (36 week) effects on the primary and secondary outcomes. Primary Outcome: The primary study outcome is the change in the Fugl-Meyer score of neurological impairment at 12 weeks relative to baseline. Secondary Outcome: Secondary outcomes include the Stroke Impact Scale and Wolf Motor Function Test. A cost-effectiveness analysis is planned but only will be conducted if robotic training is more effective than usual care. Study Abstract: CSP #558 will be a randomized, multi-center, outpatient phase II trial to assess the safety and efficacy of robot-assisted therapy for neurorehabilitation in stroke patients with moderate to severe upper extremity impairment. The target sample is 158 patients: 26 usual care, 66 intensive comparison therapy and 66 robot training. This sample size will provide 90% power to detect a 5-point mean difference in the Fugl-Meyer scale between robot training and usual care and 3-point mean difference between robot training and intensive comparison therapy. There will be one interim analysis of the primary endpoint at 12 months for the purpose of sample size re-estimation using an adaptive design. The planned study duration is 33 months with 24 months of intake and nine months of follow-up. IMPACT STATEMENT If robotic training proves to be beneficial it will not only provide a functionally-oriented and neurophysiologically appropriate therapy, but also will make more widely available high-quality, evidence-based rehabilitative care at a time when there is a shortage of experienced therapists and a progressively growing rehabilitative need for veterans and all Americans.

Official Title
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CSP #558 - Robotic Assisted Upper-Limb Neurorehabilitation in Stroke Patients

Conditions
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Stroke

Intervention / Treatment
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* Device: Robot-Assisted Therapy - MIT-MANUS System
* Other: Intensive Comparison Therapy
* Other: Usual Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A single new focal unilateral stroke with diagnosis verified by brain imaging (MRI) or CT scan that has occurred at least 6 months prior to enrollment. Age 18 years of age and older. Upper extremity Fugl-Meyer score >=7 or <=38 (max 66). (These thresholds include neither hemiplegic nor fully recovered motor function in 14 muscles of the shoulder, elbow, and wrist.) Cognitive function sufficient to understand the experiments and follow instructions (Mini-Mental Status Score of 22 and higher or interview for aphasic subjects). Willingness to avoid any new alternative arm rehabilitative approaches for the duration of the study. Written informed consent to participate in the study. Exclusion Criteria: A fixed contracture in the affected limb that prevents movement along the entire dynamic range required by either robot-assisted or intensive comparison therapy. Joint pain that occurs within the range of motion required by the intervention protocols (intensive comparison therapy and robot-assisted therapy). Enrolled in or planning to enroll in another interventional research trial that involves the upper limbs using procedures proposed to enhance or limit the function of the upper extremity (such as adjuvant rehabilitation or Botox injections) during the 36 weeks of participation. Prior experience with robot-assisted therapy or intensive comparison therapy for the upper limb as described in this specific study. A complicating medical condition that would prevent completion of the trial. Unable to complete the nine-month study, e.g., extended planned vacation. Any other known pre-existing bone diseases that might increase the risk of bone fracture or other injury from intensive comparison therapy or robot-assisted therapy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Robot-Assisted Therapy - MIT-MANUS System | Device: Robot-Assisted Therapy - MIT-MANUS System<br>* The MIT-MANUS robot consists of four modules to train the entire upper limb: module A: shoulder-elbow; module B: anti-gravity; module C: wrist, and module D: hand-unit. Training will be given for 12 weeks and is divided into 4 consecutive blocks, with 9 training sessions per block.<br>|
| Active Comparator: Arm 2<br>Intensive Comparison Therapy | Other: Intensive Comparison Therapy<br>* The intensive comparison therapy protocol being used in CSP#558 was developed and field-tested at the Burke Rehabilitation Hospital. It exposes the patient to the identical number of treatments, time, and intensity that robot treated patients will receive (12 weeks, 3 times per week). Therapy sessions can be conducted on back-to-back days if needed and on more than 3 days a week (with approval from the Study Chairman) over a treatment period of up to 14 weeks in order to complete the 36 treatment sessions. During each 1-hour session, subjects participate in therapy in four successive stages: 1) warm-up and assisted stretching; 2) active arm treatments; 3) goal-directed planar reaching, and 4) functionally based Neurodevelopment Techniques (NDT)/Bobath arm training (Bobath, 1979).<br>* Other names: ICT;|
| Other: Arm 3<br>Usual Care | Other: Usual Care<br>* The usual chronic stroke care as delivered at each participating medical center<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fugl-Meyer Assessment for Motor Recovery (FM) Scale | Fugl-Meyer (FM) is a standard instrument for the quantitative clinical assessment of motor impairment and function. In this study the upper extremity subsection of the FM was used. The FM assesses several impairment dimensions by using a 3 point ordinal scale: 0 = cannot perform, 1 = can perform partially and 2 = can perform fully. These measures are summed to an overall score is Scoring for upper extremity FM ranges from 0 (worst, completely plegic) to 66 (best, normal). Higher scores indicate better functioning. Outcome measure is the change in the FM score at 6, 12, 24 and 36 weeks relative to baseline. | 6, 12, 24 and 36 weeks minus baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stroke Impact Scale | The Stroke Impact Scale (SIS) is stroke specific, self-reported measure that evaluates function and quality of life in eight clinically relevant domains. The domains of hand function, activities of daily living, instrumental activities of daily living, mobility, and social participation were used; total score ranges from 0 to 100 with higher values indicating better functioning. Outcome is change at 6, 12, 24 and 36 weeks relative to baseline. | 6, 12, 24 and 36 weeks minus baseline | 
| Wolf Motor Function Test | The Wolf Motor Function Test (WMFT) is a functionally-based test designed to provide an objective measure of both proximal (during tasks such as lifting the hand from table to box top) and distal control (grasping pencil, bringing soda can to mouth) of the paretic arm for patients after stroke or traumatic brain injury. The WMFT consists of 17 items, of which 15 measure time to perform functional tasks. The tasks are averaged to produce a score in seconds that ranges from 0 to 120 seconds, with higher scores indicating worse functioning. Outcome measure is the change in the Wolf score at 6, 12, 24 and 36 weeks relative to baseline. | 6, 12, 24 and 36 weeks minus baseline | 
| Change in the Numeric Rating Scale (NRS) at 12 Weeks Relative to Baseline | The Numeric Rating Scale (NRS) for pain is a self report scale ranging from 0 (no Pain) to 10 (pain as bad as you can imagine). | 12 weeks minus baseline | 
| Change in the Modified Ashworth Scale for Spasticity at 12 Weeks Relative to Baseline | The Modified Ashworth Scale for spasticity is a measurement of spasticity across 9 muscle groups. Each muscle group is scored on a 0 to 5 scale with higher scores indicating worse functioning. The total score is the average score from the 9 muscle groups and ranges from 0 to 5 with higher scores indicating worse functioning. | 12 weeks minus baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stroke, Rehabilitation, Single-blind, Clinical Trial, Randomized controlled trial, Upper extremity, Robotics