Altering Activation Patterns Post-stroke

NCT ID: NCT02418949

Last Updated: 2023-10-23

Study Results

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Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

96 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-11-30

Study Completion Date

2023-12-31

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.

Conditions

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Stroke Muscle Spasticity Hemiparesis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

Cyproheptadine

Intervention Type DRUG

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)

Intervention Type OTHER

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 + 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.

Group Type PLACEBO_COMPARATOR

Placebo for Cyproheptadine

Intervention Type DRUG

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

Intervention Type OTHER

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 + 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.

Group Type ACTIVE_COMPARATOR

Cyproheptadine

Intervention Type DRUG

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

Intervention Type OTHER

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 + 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.

Group Type ACTIVE_COMPARATOR

Placebo for Cyproheptadine

Intervention Type DRUG

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)

Intervention Type OTHER

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.

Interventions

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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

Intervention Type 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

Intervention Type 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.

Intervention Type 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.

Intervention Type OTHER

Other Intervention Names

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cyproheptadine hydrochloride USP cyproheptadine HCl Periactin placebo

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

Shirley Ryan AbilityLab

OTHER

Sponsor Role lead

Responsible Party

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Elliot Roth

Medical Director, Patient Recovery Unit, Attending Physician, RIC Professor & Chairman, PM&R, Northwestern Feinberg School of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Derek G Kamper, PhD

Role: STUDY_DIRECTOR

North Carolina State University

Elliot Roth, MD

Role: PRINCIPAL_INVESTIGATOR

Shirley Ryan AbilityLab

Locations

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Rehabilitation Institute of Chicago

Chicago, Illinois, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 22275586 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19964456 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27214905 (View on PubMed)

Kamper D, Barry A, Bansal N, Stoykov ME, Triandafilou K, Vidakovic L, Seo N, Roth E. Use of cyproheptadine hydrochloride (HCl) to reduce neuromuscular hypertonicity in stroke survivors: A Randomized Trial: Reducing Hypertonicity in Stroke. J Stroke Cerebrovasc Dis. 2022 Oct;31(10):106724. doi: 10.1016/j.jstrokecerebrovasdis.2022.106724. Epub 2022 Aug 30.

Reference Type DERIVED
PMID: 36054974 (View on PubMed)

Barry AJ, Triandafilou KM, Stoykov ME, Bansal N, Roth EJ, Kamper DG. Survivors of Chronic Stroke Experience Continued Impairment of Dexterity But Not Strength in the Nonparetic Upper Limb. Arch Phys Med Rehabil. 2020 Jul;101(7):1170-1175. doi: 10.1016/j.apmr.2020.01.018. Epub 2020 Feb 28.

Reference Type DERIVED
PMID: 32113974 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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1R01HD075813-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STU00078099

Identifier Type: -

Identifier Source: org_study_id

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