Altering Activation Patterns Post-stroke

Not Applicable

Active, not recruiting

Conditions: Hemiparesis
Stroke
Muscle Spasticity

Interventions: Drug: Placebo for Cyproheptadine
Drug: Cyproheptadine
Other: Passive Cyclical Stretching
Other: Active Movement Practice (AMP)

Registration Number: NCT02418949

Lead Sponsor: Shirley Ryan AbilityLab

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 96

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo for Cyproheptadine + Stretching	Placebo for Cyproheptadine	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.
Placebo for Cyproheptadine + AMP	Placebo for Cyproheptadine	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.
Placebo for Cyproheptadine + Stretching	Passive Cyclical Stretching	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.
Cyproheptadine + Stretching	Passive Cyclical Stretching	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.
Cyproheptadine + AMP	Active Movement Practice (AMP)	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.
Placebo for Cyproheptadine + AMP	Active Movement Practice (AMP)	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.
Cyproheptadine + AMP	Cyproheptadine	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.
Cyproheptadine + Stretching	Cyproheptadine	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Change in Grip Relaxation Time (Following a Maximum Voluntary Contraction (MVC)	baseline and 9 weeks (immediately post intervention)	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.