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

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

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.

Study Overview

• Status: Completed
• Conditions: Stroke; Muscle Spasticity
• Intervention / Treatment: Behavioral: Standard Therapy; Behavioral: Optimal muscle activation therapy

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard Therapy; Coupling focal BoNT-A injections with a therapy program comprising of functional tasks.	Behavioral: Standard Therapy
Experimental: Optimal Muscle Activation Therapy; 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; 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.; Other Names: Therapy; Botulinum Toxin-A

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Collaborators: Allergan
• Investigators: Principal Investigator: George Mochizuki, PhD, Sunnybrook Health Sciences Centre

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: December 13, 2012
• First Submitted That Met QC Criteria: December 13, 2012
• First Posted (Estimate): December 18, 2012

Study Record Updates

• Last Update Posted (Estimate): May 20, 2015
• Last Update Submitted That Met QC Criteria: May 19, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Rehabilitation; Electromyography; Transcranial Magnetic Stimulation; Botulinum Toxin; Electroencephalography
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Muscle Hypertonia; Stroke; Muscle Spasticity; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A
• Other Study ID Numbers: ALSRIIIT-01