Sub-Acute Stroke Rehabilitation With AMES

Study Overview
=================
Brief Summary
-----------------
The AMES device is designed to produce functional cortical changes by:(1) assisting the subject as he/she attempts to move the limb (assisted movement) and (2) enhancing movement sensation by vibrating the muscles during movement (enhanced sensation). The primary hypothesis is that the combination of assisted movement and enhanced sensation from muscle vibration can increase the amount of motor recovery in individuals disabled by a stroke.

Detailed Description
-----------------
Approximately 700,000 U.S. citizens have a stroke each year with about half ending up with significant motor disabilities. There are an estimated 5 million stroke survivors in the U.S., making strokes the leading cause of long-term disability in the U.S.. Existing rehabilitation therapies have not been effective in returning all stroke survivors to full motor recovery. The AMES device was designed to be able to provide therapy for the hand (fingers/wrist). In this 18 treatment sessions, double-blinded, control study, AMES therapy will be provided in addition to the usual physician-ordered rehabilitation during the sub-acute period following a stroke. Those control subject who complete the Phase 1 placebo sessions will have the opportunity to cross-over to participate in a AMES treatment group for a Phase 2.

Official Title
-----------------
Sub-Acute Stroke Rehabilitation With Assisted Movement With Enhanced Sensation

Conditions
-----------------
Cerebrovascular Stroke

Intervention / Treatment
-----------------
* Device: AMES device (test)
* Device: AMES device (sham)
* Device: AMES device (crossover)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Hemispheric stroke (ischemic or hemorrhagic), cortical or sub-cortical, documented by either a CT or MRI scan and associated with residual weakness in the arm and/or leg. First time ever stroke or previous stroke with complete resolution of motor deficit, occurring ≤4 months prior to subject enrollment. Age 18-80 years old. Moderate to severe lower-extremity paresis (defined as a leg motor Fugl-Meyer score of ≥6 and ≤22 out of a possible 34. Moderate to severe upper-extremity paresis (defined as an arm motor Fugl-Meyer score of ≥6 and ≤43 out of a possible 66. Visible voluntary movement of the ankle in at least one direction: dorsiflexion or plantarflexion for the ankle and flexion or extension for the hand. At least partially functioning proprioception from the paretic arm or leg-capable of correctly identifying, ≥70% of the time, the direction of passive joint rotation (i.e., flexion-extension) with eyes closed. Physically and cognitively capable of consenting to and complying with the protocol. Score of <19 out of 63 on the 21-question version of the Beck Depression Inventory. Subject or legally authorized representative must be capable of providing informed consent.- Exclusion Criteria: Complete flaccidity of the hand, wrist, and ankle. Pathological neurological/physical conditions, other than stroke, impairing the function of the impaired arm or leg or resulting in pain in either the arm or leg. Spinal cord injury, arthritis, or fractures of affected limbs that have resulted in loss of range of motion. Peripheral nerve injury or neuropathy resulting in significant motor or sensory loss in the limb being considered for testing. Cardiopulmonary compromise including but not limited to uncontrolled hypertension or angina, deep vein thrombosis, decompensated congestive heart failure, myocardial infarction, heart irregularities, or exercise intolerance. Major active psychiatric disorder. Severe apraxia; inability to understand verbal (English) directions; or inability to communicate adequately with study personnel. Size of arm or leg incompatible with the AMES device. Severe contractures or decreased range of motion that would prohibit comfortable positioning or tolerance of the device Skin condition not able to tolerate use of the AMES device. Any progressive neurodegenerative disorder affecting the motor system. Uncontrolled seizure disorder. Current abuse of alcohol or drugs. Terminal illness with anticipated survival of <12 months. Current or planned concurrent participation in another study or clinical trial. NIH Stroke Scale, following scores: Item 1a > 0; Item 1c > 0; Item 2 > 0; Item 3 > 0; Item 9 > 2; Item 10 > 1; Item 11 > 1 (based on exam by Study Physician). Intent to receive Botox injections, initiation of antispasmodic medication, or use any other robotic (e.g., MANUS, Locomat) or stimulation device (e.g., Bioness) while participating in the AMES trial.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Single crossover for only the control group participants from the controlled part of the study.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test-Phase 1<br>The Test Group receives 18 half-hour AMES (Assisted Movement with Enhanced Sensation) treatments with the AMES device (Test) in which the hand or wrist is moved, and the subject assists the motion while vibration (60 pulses/sec) is applied to the lengthening muscle. Sessions to be scheduled preferably 2 to 3 times per week, with the 18 sessions to be completed within the 6 month anniversary date of the subject's stroke. | Device: AMES device (test)<br>* Eighteen treatment sessions for each qualifying subject limb using the AMES device. Each treatment session being 30 minutes long. Sessions to be scheduled preferable 2 to 3 times per week, with the 18 sessions to be completed within the 6 month anniversary date of the subject's stroke.<br>|
| Sham Comparator: Control-Phase 1<br>Eighteen treatment sessions for each qualifying subject limb using the AMES device (sham) programed to provide placebo therapy. Each treatment session consisting of 30 minutes of sham therapy. Sessions to be scheduled preferably 2 to 3 times per week, with the 18 sessions to be completed within the 6 month anniversary date of the subject's stroke. | Device: AMES device (sham)<br>* Eighteen treatment sessions for each qualifying subject limb using the AMES device (sham) in which the limb is moved, but no active assistance is provided by the subject and the vibration is delivered at a very low frequency to the shortening (i.e., rather than lengthening) muscle. Each treatment session to provide thirty minutes of the placebo form of AMES therapy.<br>|
| Active Comparator: Crossover-Phase 2<br>Original Control Group receives 18 half-hour crossover treatments with the AMES device (Crossover) in which the hand or wrist is moved, and the subject assists the motion while vibration (60 pulses/sec) is applied to the lengthening muscle. Sessions to be scheduled preferably 2 to 3 times per week with each session one-half hour in length. | Device: AMES device (crossover)<br>* Eighteen treatment sessions for each qualifying subject limb using the AMES device. Each treatment session being 30 minutes long. Sessions to be scheduled preferable 2 to 3 times per week, with the 18 sessions to be completed as soon as possible after the completion of Arm C-1 Sham Comparator.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fugl-Meyer Assessment Upper Limb Portion | Comprehensive measure of upper limb impairment; minimum score = 0, maximum score = 66; higher score means better outcome. Outcome measure represents the difference between post-treatment and baseline (i.e., change score). Intent is to report a change from baseline to post-treatment Phase 1 for both Test Group subjects and Control Group subjects, and to report a change from post-treatment Phase 1 to post-crossover treatment Phase 2 for Control Group subjects who elected to cross over. | Post-treatment-Phase 1 (month 3-6 post-stroke), post-crossover treatment-Phase 2 (month 5-7 post-stroke). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stroke Impact Scale | Activities of daily living questionnaire for stroke patients. Minimum overall score = 0, maximum overall score = 800. Higher scores mean better outcome. Intent is to report a change from baseline to post-treatment Phase 1 for both Test Group subjects and Control Group subjects, and to report a change from post-treatment Phase 1 to post-crossover treatment Phase 2 for Control Group subjects who elected to cross over. | Post-treatment-Phase 1 (month 3-6 post-stroke), post-crossover treatment-Phase 2 (month 5-7 post-stroke). | 
| Rancho Los Amigos Functional Test | Upper limb functional movement. Outcome measure indicates how many of 17 functional tasks could be completed. Minimum score = 0, maximum score = 17. Higher number means better outcome. Intent is to report a change from baseline to post-treatment Phase 1 for both Test Group subjects and Control Group subjects, and to report a change from post-treatment Phase 1 to post-crossover treatment Phase 2 for Control Group subjects who elected to cross over. | Post-treatment-Phase 1 (month 3-6 post-stroke), post-crossover treatment-Phase 2 (month 5-7 post-stroke). | 
| Spasticity (Modified Ashworth) Scale | Joint impedance of the fingers+wrist combined and that of the elbow. Outcome measure consists of the sum of 4 scores: (1) hand/wrist flexion, (2) hand/wrist extension, (3) elbow flexion, (4) elbow extension. Minimum value = 0, maximum value = 20. Higher score means worse outcome. Intent is to report a change from baseline to post-treatment Phase 1 for both Test Group subjects and Control Group subjects, and to report a change from post-treatment Phase 1 to post-crossover treatment Phase 2 for Control Group subjects who elected to cross over. | Post-treatment-Phase 1 (month 3-6 post-stroke), post-crossover treatment-Phase 2 (month 5-7 post-stroke). | 
| Active Motion Test Grasp | Ability to track a moving target with active grasp extension and flexion, measured as the total time in the target, in seconds. Outcome measure represents the change score from baseline to post-treatment. Minimum score = 0, maximum score = 40 s. Higher scores indicate better outcome. Intent is to report a change from baseline to post-treatment Phase 1 for both Test Group subjects and Control Group subjects, and to report a change from post-treatment Phase 1 to post-crossover treatment Phase 2 for Control Group subjects who elected to cross over. | Prior to each treatment session. Post-treatment-Phase 1 (month 3-6 post-stroke), post-crossover treatment-Phase 2 (month 5-7 post-stroke). | 
| Active Motion Wrist | Ability to track a moving target with active wrist extension and flexion, measured as the total time in the target, in seconds. Outcome measure represents the change score from baseline to post-treatment. Minimum score = 0, maximum score = 40 s. Higher scores indicate better outcome. Intent is to report a change from baseline to post-treatment Phase 1 for both Test Group subjects and Control Group subjects, and to report a change from post-treatment Phase 1 to post-crossover treatment Phase 2 for Control Group subjects who elected to cross over. | Prior to each treatment session. Post-treatment-Phase 1 (month 3-6 post-stroke), post-crossover treatment-Phase 2 (month 5-7 post-stroke). | 
| Strength Grasp Flexion | Isometric grasp flexion strength. Intent is to report a change from baseline to post-treatment Phase 1 for both Test Group subjects and Control Group subjects, and to report a change from post-treatment Phase 1 to post-crossover treatment Phase 2 for Control Group subjects who elected to cross over. | Prior to each treatment session. Post-treatment-Phase 1 (month 3-6 post-stroke), post-crossover treatment-Phase 2 (month 5-7 post-stroke). | 
| Strength Grasp Extension | Isometric grasp extension strength. Intent is to report a change from baseline to post-treatment Phase 1 for both Test Group subjects and Control Group subjects, and to report a change from post-treatment Phase 1 to post-crossover treatment Phase 2 for Control Group subjects who elected to cross over. | Prior to each treatment session. Post-treatment-Phase 1 (month 3-6 post-stroke), post-crossover treatment-Phase 2 (month 5-7 post-stroke). | 
| Strength Wrist Flexion | Isometric wrist flexion strength. Intent is to report a change from baseline to post-treatment Phase 1 for both Test Group subjects and Control Group subjects, and to report a change from post-treatment Phase 1 to post-crossover treatment Phase 2 for Control Group subjects who elected to cross over. | Prior to each treatment session. Post-treatment-Phase 1 (month 3-6 post-stroke), post-crossover treatment-Phase 2 (month 5-7 post-stroke). | 
| Strength Wrist Extension | Isometric wrist extension strength. Intent is to report a change from baseline to post-treatment Phase 1 for both Test Group subjects and Control Group subjects, and to report a change from post-treatment Phase 1 to post-crossover treatment Phase 2 for Control Group subjects who elected to cross over. | Prior to each treatment session. Post-treatment-Phase 1 (month 3-6 post-stroke), post-crossover treatment-Phase 2 (month 5-7 post-stroke). | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Sub-acute care, Robotics