Exoskeleton Robotic Assisted Gait Training in Spastic Stroke Post Botulinum Toxin A Injection

Study Overview
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Brief Summary
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The purpose of this project is to examine and compare the immediate and long-term effects of combined Botulinum toxin type A(BoNT-A) injection with exoskeleton Robotic assisted gait training (RABT) in patients with post-stroke stiff-knee gait.

Detailed Description
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The aim of the study is to evaluate the effects of BoNT-A combining with overground exoskeleton robot for patients with post-stroke stiff-knee gait. Stiff-knee gait (SKG) is a common gait pattern in patients after stroke, characterized by limited knee flexion (KF) during the swing phase of walking. Botulinum toxin A (BoNT-A) injection in rectus femoris muscle is considered the gold standard procedure to treat SKG. Patients with this gait pattern would reduce walking speed, cause toe dragging, compromise the stability of walking, increase risk of falling, and interfere with daily activities. This randomized controlled trial will contribute to the accelerated refinement and development of efficient and effective treatment programs for patients with post-stroke spastic stiff knee gait. The Robot-assisted gait training (RAGT) has the potential to be an optimal adjunctive therapy following BoNT-A treatment. Combinations of BoNT-A and rehabilitation training are suggested to optimize the treatment effect for spasticity related disabilities.

Official Title
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To Estimate the Efficacy of Botulinum Toxin A Injection Combing With Exoskeleton Robotic Assisted Gait Training in Stroke Patients With Spastic Stiff Knee Gait: Motor Function Performance and Neurophysiological Evaluation

Conditions
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Spastic Gait, Spastic

Intervention / Treatment
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* Procedure: BoNT-A injections
* Other: BoNT-A injection and robot therapy
* Other: None BoNT-A injection and robot therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ischemic or hemorrhagic stroke ≥ 3 months Age ≥ 20 years Functional Ambulation Category ≥4 Affected rectus femoris spasticity (MAS between 1+ and 2) BoNT-A treatment-naive or treated with BoNT-A ≥4 months in the affected leg before recruitment Receiving oral muscle relaxants or other medication for spasticity were on a stable dose for≥2 months Can obey simple order Exclusion Criteria: Pregnant Sensitivity to BoNT-A Infection of the skin, soft tissue in the injection area Participation in other trials Fixed contractures or bony deformities in the affected leg Previous treatment of the affected leg with neurolytic or surgical procedures (i.e., phenol block, tendon lengthening of transfer, tenotomy, muscle release, arthrodesis) Severe cardiovascular comorbidity (i.e., recent myocardial infarction, heart failure, uncontrolled hypertension, orthostatic hypotension)

Ages Eligible for Study
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Minimum Age: 20 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: BoNT-A injection and robot therapy<br>Training session included 40 minutes Robotic Therapy, the group will receive 2 sessions per week, for 12 weeks. | Procedure: BoNT-A injections<br>* Botox brand BoNT-A Purified Neurotoxin Complex, (Allergan Pharmaceuticals, Irvine, CA) will be prepared by diluting lyophilized toxin with 0.9% saline to a concentration of 33-100 U/ml. depending on the size of the target muscle. Location of the targeted muscle will be confirmed by using echo guide. The total dose range is 100 units. The dose range of each target muscle is as below:100 units in rectus femoris.<br>Other: BoNT-A injection and robot therapy<br>* Wearable overground exoskeleton lower extremity robot system will be used in this study. The robot lower extremity system consisted with bilateral motors for assisting left and right knees, a pelvis belt and chariot system for suspending the device, and thigh and shank cuffs for attaching the exoskeleton links to the user. Patients will wear receive exoskeleton lower extremity robot after BoNT-A injected in the affected rectus femoris, then start to do the functional ambulation training to do 1) walking over ground 2) walking with turning, 3) get in and out of chair, 4) crouching and rising, and 5) going up and down stairs.<br>|
| Experimental: None BoNT-A injection and robot therapy<br>Training session included 40 minutes Robotic Therapy, the group will receive 2 sessions per week, for 12 weeks. | Other: None BoNT-A injection and robot therapy<br>* Wearable overground exoskeleton lower extremity robot system will be used in this study. The robot lower extremity system consisted with bilateral motors for assisting left and right knees, a pelvis belt and chariot system for suspending the device, and thigh and shank cuffs for attaching the exoskeleton links to the user. Patients will wear receive exoskeleton lower extremity robot (do not inject BoNT-A in the affected rectus femoris), then start to do the functional ambulation training to do 1) walking over ground 2) walking with turning, 3) get in and out of chair, 4) crouching and rising, and 5) going up and down stairs.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Emory Functional Ambulation Profile(mEFAP) | The mEFAP is a clinical test that measures the time to ambulate through five common environmental terrains with or without an assistive device .It has been demonstrated to have a high inter-rater and test-retest reliability as a measure of gait capacity and functional ambulation in the post stroke patient population. The mEFAP comprises five timed tasks: (1) a 5-m walk on a hard floor; (2) a 5-m walk on a carpeted surface; (3) to rise from a chair, a 3-m walk, and return to a seated position (the timed up-and-go test); (4) a standardized obstacle course; and (5) to ascent and descent five stairs. The five timed sub scores will be adjusted by a multiplier for any necessary assistive device and then add together to derive a composite score. | Change from baseline at 5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Ashworth scale | Spasticity of skeletal muscle in lower extremity was evaluated by using the MAS scale. It uses a 8-point scale (0, 1, 1+,2, 2+, 3, 3+, 4) to score the average resistance to passive movement for each join with higher score indicating higher spasticity. The MAS has shown good reliability and validity. Investigators assessed the MAS of knee flexor/ extensor, ankle dorsiflexor/planta flexor in sitting position. The maximum of MAS scale is 4, and the minimum is 0. The higher scores mean a worse outcome. | Change from baseline at 5 months | 
| Medical Research Council scale | The MRC scale is a reliable measurement which ranges from 0 (no contraction) to 5 (normal power). Total scale combines all range and computes average scores, the higher scores mean a better outcome. The MRC scale will be used to examine the muscle strength of the affected hip flexion, knee flexion, knee extension, and ankle dorsiflexion in both sitting and standing positions. | Change from baseline at 5 months | 
| Pendulum test | Investigators use Pendulum test to evaluate the spasticity of knee extensors and record data of gyrometer deg、accelerometer deg、magnet deg. The pendular parameters (first swing excursion and relaxation index) will be extracted from an electro goniometer with 2 sensors, 15 cm above and below lateral femoral epicondyle respectively. Previous study showed the pendular parameters can provide additional ambulatory information, as complementary to the MAS . | Change from baseline at 5 months | 
| Berg Balance Scale | The BBS is a 14-item scale, which is widely used to assess balance disorders in people with stroke, each item is scored from 0 to 4 points. The reliability and validity of the BBS are well established. Investigators used BBS for balance function assessment. The higher scores mean a better outcome. | Change from baseline at 5 months | 
| Six-Minute Walking Test | The 6MWT is commonly used to assess patients' cardiovascular or respiratory problems and is regarded as a submaximal test of aerobic capacity. Investigators will use 6MWT to assess walking endurance. It is now commonly used in stroke patients and is highly reliable in this group. The maximum distance covered on a 20-m walkway in 6 mins is recorded. | Change from baseline at 5 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Spasticity, Stroke rehabilitation, Botulinum toxin type A injection, Robot, Knee