Altering Activation Patterns Post-stroke

Study Overview
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Brief Summary
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This study evaluates a new rehabilitation approach for stroke survivors in the chronic phase of recovery in which the combination of drug therapy (cyproheptadine) and active movement practice (AMP) is used to encourage increased voluntary muscle control and strength.

Detailed Description
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In this four arm parallel design you will be randomly assigned to one of 4 groups: Group 1) cyproheptadine and active movement therapy, Group 2) placebo and active movement therapy, Group 3) cyproheptadine and passive stretching, or Group 4) placebo and passive stretching. The groups will be blinded so neither you nor the research staff (or even the study doctor) will know which drug (Cyproheptadine or placebo) you receive. Only the RIC pharmacist will have access to this information until all participants complete the entire study. Although you and the research staff administering the training sessions will know if you have been assigned to the active movement practice (AMP) or passive cyclical stretching group, it is important not to discuss this information with the rater (evaluator) or the study doctor. Cyproheptadine is an anti-serotonergic and anti spastic agent. It is expected to reduce the unwanted muscle hyper excitability (one measure of spasticity) common after stroke. During the course of the treatment you will be required to make several visits per week to RIC to either be evaluated or participate in the treatment sessions. Evaluations last approximately 2 hours and will be performed at the beginning of weeks 1, 2, 3 and 4, during the middle of treatment (beginning of week 7), at the end of training (beginning of week 10) as well as a final follow-up visit one month after the end of treatment (beginning of week 14). The training sessions will occur from weeks 4 through week 9 and will involve 1.5-hr. sessions (1 hr training plus setup time) 3 times per week. The investigators hypothesize that the group receiving the combined cyproheptadine and active movement therapy will have better outcomes than the groups receiving cyproheptadine or active movement therapy alone.

Official Title
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Altering Activation Patterns in the Distal Upper Extremity After Stroke

Conditions
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Stroke, Muscle Spasticity, Hemiparesis

Intervention / Treatment
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* Drug: Cyproheptadine
* Drug: Placebo for Cyproheptadine
* Other: Active Movement Practice (AMP)
* Other: Passive Cyclical Stretching


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic, severe hand hemiparesis resulting from a single stroke (Chedoke- McMaster Stroke Assessment: Stage of Hand 2 or 3) Single stroke occurring at least 6 months prior to enrollment Spasticity Capacity to provide informed consent Exclusion Criteria: Excessive pain in paretic upper limb Hemispatial neglect (as assessed by the Behavioral Inattention Test) Apraxia (as assessed by the FABERS battery) Botulinum toxin injection in the upper extremity within the past 6 months Introduction of new anti-spasticity medication within the past 6 months Orthopaedic impairments History of seizure disorder Other major health impairment

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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cyproheptadine + AMP<br>Cyproheptadine will be titrated up to the chronic dose prior to involvement in hand therapy. Week 1 dose: 4mg taken twice daily (orally) Week 2 dose: 8mg taken twice daily (orally) Week 3 dose: (chronic dose): 8 mg taken three times daily (orally). Chronic dose will be maintained throughout the 6 weeks of Active movement practice (AMP) treatment (1 hour sessions 3x/week). Dose will be titrated down to zero in the 2 weeks following treatment. | Drug: Cyproheptadine<br>* Cyproheptadine will be titrated up to the chronic dose prior to involvement in hand therapy as well as gradually down to zero in the two weeks following treatment. Week 1 dose: 4mg taken twice daily (orally) Week 2 dose: 8mg taken twice daily (orally) Week 3 dose: (chronic dose): 8 mg taken three times daily (orally). Week 4-9: (chronic dose): 8 mg taken three times daily (orally). Week 10: 8 mg taken twice daily (orally). Week 11: 4 mg taken twice daily (orally). Week 12: no drug<br>* Other names: Periactin;Other: Active Movement Practice (AMP)<br>* Participants will alternate between active training with a custom video game and a robot active-assistive Voice and EMG-Driven Actuated (VAEDA) glove during active training occupational therapy.<br>|
| Placebo Comparator: Placebo for Cyproheptadine + Stretching<br>Placebo for Cyproheptadine will be titrated up to the chronic dose prior to involvement in hand therapy. Week 1 dose: 4mg taken twice daily (orally) Week 2 dose: 8mg taken twice daily (orally) Week 3 dose: (chronic dose): 8 mg taken three times daily (orally). Chronic dose will be maintained throughout the 6 weeks of passive cyclical stretching treatment (1 hour sessions 3x/week). Each session will involve 20 min of stretching followed by 10 minutes of rest. Dose will be titrated down to zero in the 2 weeks following treatment. | Drug: Placebo for Cyproheptadine<br>* Cyproheptadine will be titrated up to the chronic dose prior to involvement in hand therapy as well as gradually down to zero in the two weeks following treatment. Week 1 dose: 4mg taken twice daily (orally) Week 2 dose: 8mg taken twice daily (orally) Week 3 dose: (chronic dose): 8 mg taken three times daily (orally). Week 4-9: (chronic dose): 8 mg taken three times daily (orally). Week 10: 8 mg taken twice daily (orally). Week 11: 4 mg taken twice daily (orally). Week 12: no drug<br>* Other names: placebo;Other: Passive Cyclical Stretching<br>* Participants will wear the actuated device/glove for the duration of the training sessions (2 20-min stints followed by 10 min of rest) during which time the actuated glove will cyclically stretch the joints of the digits in the hand between flexion and extension while remaining passive/relaxed.<br>|
| Active Comparator: Cyproheptadine + Stretching<br>Cyproheptadine will be titrated up to the chronic dose prior to involvement in hand therapy. Week 1 dose: 4mg taken twice daily (orally) Week 2 dose: 8mg taken twice daily (orally) Week 3 dose: (chronic dose): 8 mg taken three times daily (orally). Chronic dose will be maintained throughout the 6 weeks of passive cyclical stretching treatment (1 hour sessions 3x/week). Each session will involve 20 min of stretching followed by 10 minutes of rest. Dose will be titrated down to zero in the 2 weeks following treatment. | Drug: Cyproheptadine<br>* Cyproheptadine will be titrated up to the chronic dose prior to involvement in hand therapy as well as gradually down to zero in the two weeks following treatment. Week 1 dose: 4mg taken twice daily (orally) Week 2 dose: 8mg taken twice daily (orally) Week 3 dose: (chronic dose): 8 mg taken three times daily (orally). Week 4-9: (chronic dose): 8 mg taken three times daily (orally). Week 10: 8 mg taken twice daily (orally). Week 11: 4 mg taken twice daily (orally). Week 12: no drug<br>* Other names: Periactin;Other: Passive Cyclical Stretching<br>* Participants will wear the actuated device/glove for the duration of the training sessions (2 20-min stints followed by 10 min of rest) during which time the actuated glove will cyclically stretch the joints of the digits in the hand between flexion and extension while remaining passive/relaxed.<br>|
| Active Comparator: Placebo for Cyproheptadine + AMP<br>Placebo for Cyproheptadine will be titrated up to the chronic dose prior to involvement in hand therapy. Week 1 dose: 4mg taken twice daily (orally) Week 2 dose: 8mg taken twice daily (orally) Week 3 dose: (chronic dose): 8 mg taken three times daily (orally). Chronic dose will be maintained throughout the 6 weeks of Active movement practice (AMP) treatment (1 hour sessions 3x/week). Dose will be titrated down to zero in the 2 weeks following treatment. | Drug: Placebo for Cyproheptadine<br>* Cyproheptadine will be titrated up to the chronic dose prior to involvement in hand therapy as well as gradually down to zero in the two weeks following treatment. Week 1 dose: 4mg taken twice daily (orally) Week 2 dose: 8mg taken twice daily (orally) Week 3 dose: (chronic dose): 8 mg taken three times daily (orally). Week 4-9: (chronic dose): 8 mg taken three times daily (orally). Week 10: 8 mg taken twice daily (orally). Week 11: 4 mg taken twice daily (orally). Week 12: no drug<br>* Other names: placebo;Other: Active Movement Practice (AMP)<br>* Participants will alternate between active training with a custom video game and a robot active-assistive Voice and EMG-Driven Actuated (VAEDA) glove during active training occupational therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean Completion Time for Graded Wolf Motor Function Test (GWMFT) | GWMFT is a clinical outcome measure comprised of 15 timed tasks focusing on upper extremity function. Maximum allowable time per task is 120 seconds. | baseline and 9 weeks (immediately post intervention) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Grip Relaxation Time (Following a Maximum Voluntary Contraction (MVC) | Following a maximum voluntary contraction (MVC) -- Time (s) required for muscle electromyographic (EMG) signals to reduce to within 3 SD of pre-MVC EMG activity. | baseline and 9 weeks (immediately post intervention) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hand, rehabilitation, active movement training, passive cyclical stretching