Effects of Robot-Assisted Combined Therapy in Upper Limb Rehabilitation in Stroke Patients

Study Overview
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Brief Summary
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The main purpose of this study is to examine the treatment effects and the combined-therapy of the robot-assisted therapy (RAT) by using two groups of combined-therapy with different sensory feedback and one group of unilateral RAT in the investigators trial to compare the relative treatment effects to mirror therapy group, bilateral RAT, and conventional rehabilitation (CR) considering motor ability, basic daily functions, mobility, quality of life, and kinematic variables.

Detailed Description
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Stroke remains a leading cause of permanent disability in Taiwan and many other countries. The high incidence of stroke and the decreased mortality from stroke which imply the urgent needs for effective rehabilitation. Various contemporary rehabilitation interventions focused on restoring upper limb motor function have been advocated for stroke rehabilitation. Robot-assisted therapy (RAT), one current prominent activity-based approach, has emerged that incorporates therapeutic elements for success in stroke motor rehabilitation: combined with neuromuscular electrical stimulation and mirror therapy into its design. However, scientific evidence for the effects of the RAT and its combined-therapy on functional outcomes (e.g., motor and daily functions) in stroke patients remains limited. Furthermore, there is a need to identify the proper protocol and intervention type. This research project will use randomized controlled trial design to address these issues. The main purpose of this study is to examine the treatment effects and the combined-therapy of the RAT by using two groups of combined-therapy with different sensory feedback and one group of unilateral RAT in our trail to compare the relative treatment effects to mirror therapy group, bilateral RAT, and conventional rehabilitation (CR) considering motor ability, basic daily functions, mobility, quality of life, and kinematic variables. The inclusion criteria of subjects are first-ever unilateral stroke with more than 3 months onset ; (2) an initial UL subsection of the Fugl-Meyer Assessment score of 18 to 56 indicating moderate to severe and moderate UL movement impairment; (3) no excessive spasticity in any of the joints of the affected UL (shoulder, elbow, wrist, fingers); (4) be able to follow study instructions and perform study tasks; (5) without upper limb fracture within 3 months; (6) lack of participation in any experimental rehabilitation or drug studies during the study period; (7) welling to provide written informed consent ; and (8) able to realize and respond to oral instructions. Patients with neural or psychological medical history, recurrent stroke or attack by epilepsy during the intervention will be excluded. Expected sample size is 120. Subjects will be randomly assigned to one of the six groups: (1) robot-assisted therapy combined with neuromuscular electrical stimulation (RAT-NMES) ; (2) robot-assisted therapy combined with mirror therapy (RAT-MT) ; (3) mirror therapy group; (4) unilateral robot-assisted therapy group ; (5) bilateral robot-assisted therapy and (6) conventional rehabilitation (CR). All subjects in the study will receive treatment from registered occupational therapist 1.5 hours each day, five days a week for four weeks. Pretest and posttest will be hold before and after the intervention to check if the subjects had any improvement. The outcome measures are kinematic analysis of the upper and lower limb movement variables, the Fugl-Meyer Assessment (FMA), Medical Research Council scale (MRC), MYOTON-3, accelerometers, Functional Ambulation Category (FAC), Ten-meter walk test, Functional Independence Measure (FIM), Stroke Impact Scale (SIS), Action Research Arm Test (ARAT), Wolf Motor Function Test (WMFT), ABILHAND, Motor Activity Log (MAL), and Modified Ashworth Scale (MAS). All the data will be calculated by SPSS 13.0. Subject's age, sex, time after stroke in each group will be compared by descriptive statistics. The change of outcome measures after intervention in each group will be calculated by ANOVA to see if combined therapy had better effectiveness than the other groups.

Official Title
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Effects of Robot-Assisted Combined Therapy in Upper Limb Rehabilitation in Stroke Patients

Conditions
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Cerebrovascular Accident

Intervention / Treatment
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* Behavioral: RAT-NMES
* Behavioral: RAT-MT
* Behavioral: Mirror therapy
* Behavioral: Unilateral RAT
* Behavioral: Bilateral RAT
* Behavioral: Conventional rehabilitation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: first-ever unilateral stroke with more than 3 months onset ; an initial UL subsection of the Fugl-Meyer Assessment score of 18 to 56 indicating moderate to severe and moderate UL movement impairment; no excessive spasticity in any of the joints of the affected UL (shoulder, elbow, wrist, fingers); be able to follow study instructions and perform study tasks;and willing to provide written informed consent. Exclusion Criteria: with neural or psychological medical problem that may influence the study; with severe joint pain; with upper limb fracture within 3 months; participation in any experimental rehabilitation or drug studies during the study period; and refusing to provide written informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RAT-NMES<br>The combined treatment of robot-assisted therapy and neuromuscular electrical stimulation. | Behavioral: RAT-NMES<br>* This combined RAT- treatment involves the same protocol as the RAT regimen except that patients receive neuromuscular electrical stimulation (NMES) concurrently with RAT.<br>* Other names: RAT-neuromuscular electrical stimulation;|
| Experimental: RAT-MT<br>The combined treatment of robot-assisted therapy and mirror therapy. | Behavioral: RAT-MT<br>* This combined RAT- treatment involves the same protocol as the RAT regimen except that patients receive mirror therapy instead of functional activities training after RAT.<br>* Other names: RAT-mirror therapy;|
| Active Comparator: Mirror therapy<br>Patients practice motion in a mirror box, and look into mirror while practicing. | Behavioral: Mirror therapy<br>* This protocol includes mirror therapy and functional training in a session. The treatment intensity is 1.5 hours/day, 5 days/week, for 4 weeks. MT focuses on symmetrical bimanual movements and simultaneously observing the mirror visual feedback reflected by the unaffected upper extremity.<br>* Other names: MT;|
| Experimental: Unilateral RAT<br>Unilateral robot-assisted therapy provided by InMotion Isokinetic Testing and Evaluation System. | Behavioral: Unilateral RAT<br>* This protocol includes warm-up, unilateral RAT, and functional activities training. The treatment intensity is 1.5 hours/day, 5days/week for 4 consecutive weeks. The unilateral RAT session uses the robot-assisted arm trainer, InMotion Isokinetic Testing and Evaluation System.<br>* Other names: URAT;|
| Active Comparator: Bilateral RAT<br>Bilateral robot-assisted therapy provided by Bi-Manu-Track. | Behavioral: Bilateral RAT<br>* This protocol includes warm-up, bilateral RAT, and functional activities training. The treatment intensity is 1.5 hours/day, 5days/week for 4 consecutive weeks. The unilateral RAT session uses the robot-assisted arm trainer, Bi-Manu-Track (Reha-Stim Co., Berlin, Germany).<br>* Other names: BRAT;|
| Active Comparator: Conventional rehabilitation<br>Conventional rehabilitation provided by therapist. | Behavioral: Conventional rehabilitation<br>* Participants in this group receive a structured protocol based on occupational therapy such as neuro-developmental techniques and task-oriented approach. The treatment dose is matched to RAT and MT groups.<br>* Other names: CT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change of kinematic analyses | A 7-camera motion-analysis system (VICON MX, Oxford Metrics Inc., Oxford, UK) was used.The variables of reaction time (second), movement time (second), total displacement (mm), peak velocity (mm/second), percentage of peak velocity, joint recruitments (degree), maximum shoulder and elbow cross-correlation and variables of gait pattern were collected. | within three days before and immediately after the intervention | 
| change of Fugl-Meyer Assessment | The upper-extremity subscale of the FMA will be used to assess motor impairment. The 33 upper limb items measure the movement and reflexes of the shoulder/elbow/forearm, wrist, hand, and coordination/speed. They are scored on a 3-point ordinal scale (0-cannot perform, 1-performs partially, 2-performs fully). The maximum score is 66, indicating optimal recovery. The sub-score of a proximal shoulder/elbow (FMA s/e: 0-42) and a distal hand/wrist (FMA h/w: 0-24) will be also calculated to investigate the treatment effects on separate upper extremity elements. The reliability, validity, and responsiveness of the FMA in stroke patients have been shown to be good. | within three days before and immediately after the intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change of 10-Meter Walk Test (10MWT) | The 10MWT assess mobility function by measuring the time and the numbers of strides required to walk 10 meters under two conditions: (1) with the self-pace of each participant (self-pace); (2) with the speed that the participants walked as soon as possible. The velocity and stride length of the participant are calculated. Research has validated the 10MWT in measuring mobility in stroke. | within three days before and immediately after the intervention | 
| change of Wolf Motor Function Test | The WMFT requires the participant to perform 15 function-based and 2 strength-based tasks. The tasks are averaged to produce a score in seconds that ranges from 0 to 120 seconds. For functional ability scoring, we used a 6-point ordinal scale where 0 indicates does not attempt with the involved arm and 5 indicates arm does participate; movement appears to be normal. | within three days before and immediately after the intervention | 
| change of Functional Independence Measure | The FIM consists of 18 items grouped into 6 subscales measuring self-care, sphincter control, transfer, locomotion, communication, and social cognition ability. Each item is rated from 1 to 7 (maximum score 126) based on the required level of assistance to perform the tasks (e.g., 1-complete assistance and 7-complete independence). A higher score on any subscale indicates a less disability. | within three days before and immediately after the intervention | 
| change of The Action Research Arm Test | The ARAT assesses the ability to handle objects with 19 items divided into 4 subscales of grasp, grip, pinch, and gross movement by 4-level ordinal scale. Higher the score, better the performance. | within three days before and immediately after the intervention |