Assessment and Management of Post-Stroke Spasticity With Botulinum Toxin-A

Study Overview
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Brief Summary
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Within the first year after stroke, approximately 38% of stroke survivors experience an increased resistance to movement, also called spasticity. One type of treatment that is approved for stroke survivors in Canada that could reduce spasticity is the injection of Botulinum toxin (BTX) into the affected muscle. While BTX reduces spasticity, there is limited evidence to show that BTX administration leads to functional improvements. This may occur because the outcomes aren't sensitive enough to detect change, some people may have better responses to BTX, or because BTX hasn't been paired with the right exercises to improve function. The aims of this research are: i) to determine if there is a way of improving the markers that measure change in response to treatment; and ii) to identify the ideal type of exercise that should be paired with BTX to allow the drug to have it greatest effect. There are two primary research questions: a) What are the measures that will indicate whether a person with post-stroke spasticity will benefit from BTX therapy? It is hypothesized that EMG latency and amplitude, for those who best respond to BTX, will differ from those who demonstrate a weaker response to BTX; b)What is the ideal training approach for improving muscle function in stroke survivors receiving BTX injections? It is hypothesized that a training protocol that focuses on optimizing specific muscle activation patterns will demonstrate better outcomes than a training program designed to improve function.

Official Title
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Novel Assessment and Treatment Approaches for Detecting and Facilitating Functional Improvements in Post-Stroke Spasticity With Botulinum Toxin-A

Conditions
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Stroke, Muscle Spasticity

Intervention / Treatment
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* Behavioral: Optimal muscle activation therapy
* Behavioral: Standard Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: >120 days post first ischemic stroke Unilateral spasticity (MAS ≥ 1) of the wrist or elbow >18 years of age Medical referral for focal BoNT-A injections Residual active control of the wrist or elbow Exclusion Criteria: Underlying neuromuscular disorders (i.e. ALS, neuropathies, myasthenia gravis) Inability to provide informed consent or communicate in English Bilateral paresis/spasticity Contractures Prescribed anti-spastic medication

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: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard Therapy<br>Coupling focal BoNT-A injections with a therapy program comprising of functional tasks. | Behavioral: Standard Therapy<br> <br> |
| Experimental: Optimal Muscle Activation Therapy<br>Coupling focal BoNT-A injections with a motor training program that focuses on developing and maintaining activation patterns in the muscle treated with BoNT-A. | Behavioral: Optimal muscle activation therapy<br>* The proposed study uses a longitudinal, within-subject, pre/post intervention, cross-over design. All participants will complete each of 4 study phases (each 12 weeks long). These include: a) focal BTX injections in combination with either Standard Therapy or Optimal Muscle Activity Therapy; b) a three-month period where no treatment is given; c) focal BTX injections in combination either Standard Therapy or Optimal Muscle Activation Therapy; d) another three-month period where no treatment is given. The order of treatment phases will be counter-balanced across participants.<br>* Other names: Therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amplitude and timing of electromyographic signals (EMG) | Change in electrical activation patterns of the target muscle(s) (i.e. muscle receiving BTX injection) and the antagonist muscle. | Baseline, Month 1, Month 2, Month 3, Month 6, Month 7, Month 8, Month 9, Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Motor Evoked Potential amplitude | To measure the change in cortical excitability associated with the intervention. | Baseline, Month 1, Month 2, Month 3, Month 6, Month 7, Month 8, Month 9, Month 12 | 
| Goal Attainment Scale | Change in Goal Attainment Scale | Baseline, 6 Months | 
| Modified Ashworth Scale | Change in Modified Ashworth Scale | Baseline, Month 1, Month 2, Month 3, Month 6, Month 7, Month 8, Month 9, Month 12 | 
| Modified Tardieu Scale | Change in Modified Tardieu Scale | Baseline, Month 1, Month 2, Month 3, Month 6, Month 7, Month 8, Month 9, Month 12 | 
| Frequency and amplitude of electroencephalographic (EEG) activity | Measurement of event-related cortical activity | Baseline, Month 1, Month 2, Month 3, Month 6, Month 7, Month 8, Month 9, Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Botulinum Toxin, Rehabilitation, Electromyography, Electroencephalography, Transcranial Magnetic Stimulation