Altering Activation Patterns Post-stroke

• Sponsor: Shirley Ryan AbilityLab (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02418949
• Collaborator: National Institutes of Health (NIH) (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
• Enrollment: 96
• Location: 1
• Arms: 4
• Duration (Months): 83
• Patients Per Site Per Month: 1.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Stroke; Muscle Spasticity; Hemiparesis	Drug: Cyproheptadine; Drug: Placebo for Cyproheptadine; Other: Active Movement Practice (AMP); Other: Passive Cyclical Stretching	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 96 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Altering Activation Patterns in the Distal Upper Extremity After Stroke
• Study Start Date: Nov 1, 2015
• Actual Primary Completion Date: Aug 1, 2019
• Anticipated Study Completion Date: Oct 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cyproheptadine + 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.	Drug: Cyproheptadine; 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; Other Names: cyproheptadine hydrochloride USP cyproheptadine HCl Periactin ; Other: Active Movement Practice (AMP); 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.
Placebo Comparator: Placebo for Cyproheptadine + 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.	Drug: Placebo for Cyproheptadine; 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; Other Names: placebo ; Other: Passive Cyclical Stretching; 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.
Active Comparator: Cyproheptadine + 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.	Drug: Cyproheptadine; 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; Other Names: cyproheptadine hydrochloride USP cyproheptadine HCl Periactin ; Other: Passive Cyclical Stretching; 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.
Active Comparator: Placebo for Cyproheptadine + 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.	Drug: Placebo for Cyproheptadine; 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; Other Names: placebo ; Other: Active Movement Practice (AMP); 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.

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rehabilitation Institute of Chicago	Chicago	Illinois	United States	60611

Sponsors and Collaborators

• Shirley Ryan AbilityLab
• National Institutes of Health (NIH)
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Study Director: Derek G Kamper, PhD, North Carolina State University
• Principal Investigator: Elliot Roth, MD, Shirley Ryan AbilityLab

Study Documents (Full-Text)

• Study Protocol - Jun 23, 2020
• Statistical Analysis Plan - Jun 4, 2014
• Informed Consent Form - May 17, 2019

More Information

Publications

• Ochoa J, Dev Narasimhan YJ, Kamper DG. Development of a portable actuated orthotic glove to facilitate gross extension of the digits for therapeutic training after stroke. Annu Int Conf IEEE Eng Med Biol Soc. 2009;2009:6918-21. doi: 10.1109/IEMBS.2009.5333630.
• Ochoa JM, Listenberger M, Kamper DG, Lee SW. Use of an electromyographically driven hand orthosis for training after stroke. IEEE Int Conf Rehabil Robot. 2011;2011:5975382. doi: 10.1109/ICORR.2011.5975382.
• Thielbar KO, Triandafilou KM, Fischer HC, O'Toole JM, Corrigan ML, Ochoa JM, Stoykov ME, Kamper DG. Benefits of Using a Voice and EMG-Driven Actuated Glove to Support Occupational Therapy for Stroke Survivors. IEEE Trans Neural Syst Rehabil Eng. 2017 Mar;25(3):297-305. doi: 10.1109/TNSRE.2016.2569070. Epub 2016 May 17.

• Responsible Party: Elliot Roth, Medical Director, Patient Recovery Unit, Attending Physician, RIC Professor & Chairman, PM&R, Northwestern Feinberg School of Medicine, Shirley Ryan AbilityLab
• ClinicalTrials.gov Identifier: NCT02418949
• Other Study ID Numbers: STU00078099; 1R01HD075813-01A1
• First Posted: Apr 17, 2015
• Last Update Posted: Jul 13, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Elliot Roth, Medical Director, Patient Recovery Unit, Attending Physician, RIC Professor & Chairman, PM&R, Northwestern Feinberg School of Medicine, Shirley Ryan AbilityLab: hand; rehabilitation; active movement training; passive cyclical stretching
• Additional relevant MeSH terms: Muscle Spasticity; Stroke; Paresis; Cyproheptadine

Study Results

Participant Flow

Arm/Group Title	Cyproheptadine + AMP	Placebo for Cyproheptadine + Stretching	Cyproheptadine + Stretching	Placebo for Cyproheptadine + AMP
Arm/Group Description	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: 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 Active Movement Practice (AMP): 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.	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: 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 Passive Cyclical Stretching: 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.	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: 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 Passive Cyclical Stretching: 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.	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: 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 Active Movement Practice (AMP): 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.
Period Title: Overall Study
STARTED	23	22	26	25
COMPLETED	20	21	23	24
NOT COMPLETED	3	1	3	1

Baseline Characteristics

Arm/Group Title	Cyproheptadine + AMP	Placebo for Cyproheptadine + Stretching	Cyproheptadine + Stretching	Placebo for Cyproheptadine + AMP	Total
Arm/Group Description	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: 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 Active Movement Practice (AMP): 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.	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: 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 Passive Cyclical Stretching: 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.	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: 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 Passive Cyclical Stretching: 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.	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: 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 Active Movement Practice (AMP): 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.	Total of all reporting groups
Overall Participants	22	22	25	25	94
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60 (8.1)	57.1 (11.2)	58.9 (13.1)	57.3 (9.5)	58.3 (10.6)
Sex: Female, Male (Count of Participants)
Female	8 36.4%	9 40.9%	10 40%	8 32%	35 37.2%
Male	14 63.6%	13 59.1%	15 60%	17 68%	59 62.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 4.5%	21 95.5%	23 92%	23 92%	68 72.3%
Not Hispanic or Latino	21 95.5%	1 4.5%	2 8%	2 8%	26 27.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	3 13.6%	0 0%	2 8%	1 4%	6 6.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	11 50%	9 40.9%	12 48%	13 52%	45 47.9%
White	8 36.4%	13 59.1%	11 44%	11 44%	43 45.7%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Chedoke McMaster Scale of Hand (Count of Participants)
Equal or less than 2	6 27.3%	11 50%	6 24%	8 32%	31 33%
Equal or Greater than 3	16 72.7%	11 50%	19 76%	17 68%	63 67%
Fugl-Meyer Upper Extremity Assessment (Score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Score]	15 (8.1)	12.9 (5.5)	16.1 (7.1)	15.6 (5.6)	15 (6.6)
Lesion Side (Count of Participants)
Left	10 45.5%	7 31.8%	11 44%	12 48%	40 42.6%
Right	12 54.5%	15 68.2%	14 56%	13 52%	54 57.4%
Time Since Stroke onset (Years) (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	5.9 (4.3)	5.4 (5.3)	5.6 (4.7)	8.5 (8.6)	6.4 (6.0)

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cyproheptadine + AMP	Placebo for Cyproheptadine + Stretching	Cyproheptadine + Stretching	Placebo for Cyproheptadine + AMP
Arm/Group Description	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: 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 Active Movement Practice (AMP): 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.	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: 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 Passive Cyclical Stretching: 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.	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: 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 Passive Cyclical Stretching: 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.	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: 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 Active Movement Practice (AMP): 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.
Measure Participants	20	21	23	24
Mean (95% Confidence Interval) [Seconds]	-3.66	-0.51	-4.00	-3.89

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cyproheptadine + AMP	Placebo for Cyproheptadine + Stretching	Cyproheptadine + Stretching	Placebo for Cyproheptadine + AMP
Arm/Group Description	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: 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 Active Movement Practice (AMP): 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.	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: 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 Passive Cyclical Stretching: 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.	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: 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 Passive Cyclical Stretching: 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.	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: 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 Active Movement Practice (AMP): 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.
Measure Participants	20	21	23	24
Mean (95% Confidence Interval) [Seconds]	-1.66	-0.96	-1.06	-2.65

Adverse Events

Time Frame	Adverse events were collected during study enrollment, from screening to the final follow up appointment (13 total weeks after initial screening)
Arm/Group Title	Cyproheptadine + AMP		Placebo for Cyproheptadine + Stretching		Cyproheptadine + Stretching		Placebo for Cyproheptadine + AMP
Arm/Group Description	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: 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 Active Movement Practice (AMP): 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.		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: 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 Passive Cyclical Stretching: 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.		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: 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 Passive Cyclical Stretching: 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.		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: 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 Active Movement Practice (AMP): 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.
All Cause Mortality
	Cyproheptadine + AMP		Placebo for Cyproheptadine + Stretching		Cyproheptadine + Stretching		Placebo for Cyproheptadine + AMP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/22 (0%)		0/26 (0%)		0/25 (0%)
Serious Adverse Events
	Cyproheptadine + AMP		Placebo for Cyproheptadine + Stretching		Cyproheptadine + Stretching		Placebo for Cyproheptadine + AMP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/23 (8.7%)		2/22 (9.1%)		1/26 (3.8%)		0/25 (0%)
Cardiac disorders
CHF Exacerbation	0/23 (0%)	0	0/22 (0%)	0	1/26 (3.8%)	1	0/25 (0%)	0
Coronary Blockage	0/23 (0%)	0	1/22 (4.5%)	1	0/26 (0%)	0	0/25 (0%)	0
Gastrointestinal disorders
Bowel Obstruction	1/23 (4.3%)	1	0/22 (0%)	0	0/26 (0%)	0	0/25 (0%)	0
Nervous system disorders
Convulsions	0/23 (0%)	0	1/22 (4.5%)	1	0/26 (0%)	0	0/25 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pneumonia	1/23 (4.3%)	1	0/22 (0%)	0	0/26 (0%)	0	0/25 (0%)	0
Skin and subcutaneous tissue disorders
Foot Wound	1/23 (4.3%)	1	0/22 (0%)	0	0/26 (0%)	0	0/25 (0%)	0
Other (Not Including Serious) Adverse Events
	Cyproheptadine + AMP		Placebo for Cyproheptadine + Stretching		Cyproheptadine + Stretching		Placebo for Cyproheptadine + AMP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/23 (82.6%)		15/22 (68.2%)		18/26 (69.2%)		21/25 (84%)
Gastrointestinal disorders
Constipation	6/23 (26.1%)	6	5/22 (22.7%)	5	6/26 (23.1%)	6	6/25 (24%)	6
General disorders
Dry Mouth	9/23 (39.1%)	9	9/22 (40.9%)	9	11/26 (42.3%)	11	9/25 (36%)	9
Low Energy	10/23 (43.5%)	10	7/22 (31.8%)	7	12/26 (46.2%)	12	4/25 (16%)	4
Restless/Jittery	4/23 (17.4%)	4	3/22 (13.6%)	3	4/26 (15.4%)	4	3/25 (12%)	3
Slowness/Trouble getting moving	3/23 (13%)	3	6/22 (27.3%)	6	7/26 (26.9%)	7	5/25 (20%)	5
Sleep Problems	3/23 (13%)	3	4/22 (18.2%)	4	5/26 (19.2%)	5	5/25 (20%)	5
Memory Problems	2/23 (8.7%)	2	8/22 (36.4%)	8	9/26 (34.6%)	9	4/25 (16%)	4
Metabolism and nutrition disorders
Weight Gain	7/23 (30.4%)	7	6/22 (27.3%)	6	9/26 (34.6%)	9	5/25 (20%)	5
Psychiatric disorders
Low Motivation	1/23 (4.3%)	1	5/22 (22.7%)	5	9/26 (34.6%)	9	2/25 (8%)	2
Renal and urinary disorders
Frequent Urination	7/23 (30.4%)	7	6/22 (27.3%)	6	7/26 (26.9%)	7	4/25 (16%)	4
Difficulty Urinating	4/23 (17.4%)	4	2/22 (9.1%)	2	2/26 (7.7%)	2	2/25 (8%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.