Maraviroc to Augment Rehabilitation Outcomes After Stroke

NCT03172026 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: IRB#16-001733
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 3

Brief Summary

After stroke, the combination of progressive skills practice in an adequate dose, exercise for fitness, and reduced sedentary time will augment motor and cognitive outcomes. Sensorimotor and cognitive improvements after stroke often reach a general plateau by approximately 12 weeks after onset, however. Drugs that might enhance learning or neural repair, as well as other molecular and synaptic adaptations that occur during skills training and fitness exercise, might extend that recovery curve, although to date only fluoxetine has given any hint of this. Most trials have tested agents that modulate neurotransmitters. Several very recent preclinical experiments and observational studies in patients after stroke suggest that the commercially available medication, Maraviroc, a CCR5 antagonist, may augment skills learning during rehabilitation training, especially during the first three months after onset, by affecting CREB and synaptic plasticity. The investigators will carry out a randomized controlled trial of Maraviroc in patients with disabilities severe enough to have required inpatient stroke rehabilitation and, based on our preclinical data, who can start the drug intervention within 6 weeks of stroke onset. The investigators will compare usual post-stroke care plus placebo versus Maraviroc given for 8 weeks in 60 participants. However, to try to maximize the amount of practice that is most relevant to the primary outcome measurements and determine whether or not Maraviroc can enhance the effects of training, as hypothesized, all participants will be tele-monitored by mobile health devices and will receive weekly telephonic encouragement, based on device data, to walk, reduce sedentary time, and reach and grasp in the home in between usual care therapies. Compliance, serial motor changes over time, and self-management skills in making use of the telerehabilitation devices will be a nested substudy of feasibility of remote monitoring and feedback.

Conditions

Stroke

Keywords

Telerehabilitation; Maraviroc

Outcome Measures

Primary Outcomes (2)

• Change in 10 Meter Walk Test

  Timed walking speed over 10 meters. The evaluable sample size of 30 in each group will have 80% power to detect a difference in means of -0.206 (m/s), the difference between an assumed usual care walking speed of 0.51 (SD=0.28) and an assumed intervention group mean walking speed of 0.716. This assumes a common standard deviation in the two groups and a two group t-test with a 0.05 two-sided significance level. The estimates for the mean and standard deviation for walking speed come from the LEAPS RCT (Duncan, N Engl J Med, 2011). The t-test used for the power calculation is a simplification of the mixed effects analysis plan for the primary endpoints.

  Baseline, 6 months post

• Change in Action Research Arm Test

  Assessment of upper extremity function. Our sample size of 30 for each group is based on a statistical power of 80% with an alpha of 5% for detecting a meaningful difference of 6 points, i.e., a 10% change, which has been suggested by several completed trials. In a stroke trial, the standard deviation was 8 points measured at 2 weeks post stroke.

  Baseline, 6 months post

Secondary Outcomes (9)

• Change in Fugl-Meyer Motor Score

  Baseline, within 5 days of last medication dose (8 weeks), at 6 months post stroke

• Change in Stroke Impact Scale

  Baseline, within 5 days of last medication dose (8 weeks), at 6 months post stroke

• Change in 6 Minute Walking Distance

  Baseline, within 5 days of last medication dose (8 weeks), at 6 months post stroke

• Change in Physical Activity Enjoyment Scale

  Baseline, within 5 days of last medication dose (8 weeks), at 6 months post stroke

• Change in Activity Self Efficacy

  Baseline, within 5 days of last medication dose (8 weeks), at 6 months post stroke

Study Arms (2)

Maraviroc + Augmented Rehabilitation

EXPERIMENTAL

Participants will take Maraviroc 300 mg daily for 60 days, plus receive rehabilitation therapy as prescribed by the doctors and via telerehabilitation.

Drug: Maraviroc 300 mg; Behavioral: Rehabilitation therapy

Placebo + Augmented Rehabilitation

PLACEBO COMPARATOR

Participants will take placebo 300 mg daily for 60 days, plus receive rehabilitation therapy as prescribed by the doctors and via telerehabilitation.

Behavioral: Rehabilitation therapy; Drug: Placebo 300 mg

Interventions

Maraviroc 300 mg DRUG

FDA approved chemokine receptor (CCR5) inhibitor. Maraviroc will be started within two weeks of discharge from inpatient rehabilitation, which most often will occur from 4-6 weeks after stroke onset.

Also known as: Selzentry

Maraviroc + Augmented Rehabilitation

Rehabilitation therapy BEHAVIORAL

All participants will have routine outpatient or home health physical and occupational therapy after inpatient discharge as prescribed by their physicians. Each group will be contacted weekly by phone to help maintain interest in the trial, count the number of usual care physical and occupational therapy completed, assure use of the assigned medication, ask about possible adverse reactions, and to encourage them to be active. The coordinator will obtain this information and provide the feedback using a standard script and checklist. A unique aspect of this trial is a telerehabilitation component that aims to give feedback to all participants to practice with the affected arm and walk daily.

Maraviroc + Augmented Rehabilitation; Placebo + Augmented Rehabilitation

Placebo 300 mg DRUG

Matched placebo will be started within two weeks of discharge from inpatient rehabilitation, which most often will occur from 4-6 weeks after stroke onset.

Placebo + Augmented Rehabilitation

Eligibility Criteria

• Age: 30 Years - 86 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Transfer to inpatient rehabilitation within 4 weeks of stroke onset
• Single ischemic or subcortical hemorrhagic infarct;
• At the time of randomization, hemiparesis with 4/5 or less strength at the hip and ankle flexors and extensors
• Functional Independence Measure (FIM) score for ambulation ≥3 to walk at least 10 steps;
• Caregiver available for at least two hours a day for practice and transportation when needed;
• Adequate language skills to read and understand the Informed Consent and retain information during daily therapies.

You may not qualify if:

• Prior stroke with persisting motor impairment or disability;
• Limited resources or illness that will not enable a return to living outside of a facility;
• Any medical condition that had limited daily physical activity to walking no more than 2 blocks outdoors prior to the stroke (e.g., claudication, congestive heart failure or lower extremity pain);
• History of dementia or Mini Mental State Examination score \<24;
• History of hepatitis or elevated hepatic transaminases or bilirubin;
• History of renal insufficiency or serum creatinine over 1.6;
• Cancer or other chronic illness that makes 3-year survival unlikely or will detract from the ability to carry out exercise and skills practice.

Sponsors & Collaborators

• University of California, Los Angeles: lead

Study Sites (3)

California Rehabilitation Institute

Los Angeles, California, 90067, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Burke Neurological Research Institute

White Plains, New York, 10605, United States

Location

MeSH Terms

Conditions

Stroke

Interventions

Maraviroc; Rehabilitation

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services

Results Point of Contact

• Title: Dr. Bruce H. Dobkin
• Organization: University of California Los Angeles

BDobkin@mednet.ucla.edu

310-206-6500

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: We plan a parallel group, randomized controlled pilot trial at 3 sites, UCLA, Yale and Burke Neurological Institute in White Plains, NY, to gather enough entries in a shorter time and to better generalize the results of this phase II/III pilot trial.

Study Record Dates

• First Submitted: May 25, 2017
• First Posted: May 31, 2017
• Study Start: August 1, 2019
• Primary Completion: October 1, 2020
• Study Completion: October 1, 2020
• Last Updated: August 3, 2021
• Results First Posted: August 3, 2021

Record last verified: 2021-07

Locations

US (3)