Maraviroc to Augment Rehabilitation Outcomes After Stroke (MAROS)

• Sponsor: University of California, Los Angeles
• Collaborator: Burke Rehabilitation Hospital
• Information provided by (Responsible Party): Bruce H. Dobkin, University of California, Los Angeles

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Stroke	Drug: Maraviroc 300 mg; Behavioral: Rehabilitation therapy; Drug: Placebo 300 mg	Phase 2; Phase 3

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Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	60 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Intervention Model Description:	We plan a parallel group, randomized controlled pilot trial at two sites, UCLA and Burke Rehabilitation Center 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.
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Maraviroc to Augment Rehabilitation Outcomes After Stroke
Actual Study Start Date :	May 1, 2018
Estimated Primary Completion Date :	July 2019
Estimated Study Completion Date :	December 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Maraviroc + Augmented Rehabilitation; 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; 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.; Other Name: Selzentry; Behavioral: Rehabilitation therapy; 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.
Placebo Comparator: Placebo + Augmented Rehabilitation; 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; 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.; Drug: Placebo 300 mg; 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.

Outcome Measures

Primary Outcome Measures :

1. 10 Meter Walk Test [ Time Frame: Baseline, 6 months post ]
   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.
2. Action Research Arm Test [ Time Frame: Baseline, 6 months post ]
   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.

Secondary Outcome Measures :

1. Fugl-Meyer Motor score [ Time Frame: Baseline, within 5 days of last medication dose (8 weeks), at 6 months post stroke ]
   Assessment of arm and leg impairment after stroke
2. Stroke Impact Scale [ Time Frame: Baseline, within 5 days of last medication dose (8 weeks), at 6 months post stroke ]
   Self-report questionnaire on quality of life post-stroke
3. 6 minute walking distance [ Time Frame: Baseline, within 5 days of last medication dose (8 weeks), at 6 months post stroke ]
   Distance walked in a 6 minute time period
4. Physical Activity Enjoyment Scale [ Time Frame: Baseline, within 5 days of last medication dose (8 weeks), at 6 months post stroke ]
   Self-report questionnaire related to exercise enjoyment
5. Activity Self Efficacy [ Time Frame: Baseline, within 5 days of last medication dose (8 weeks), at 6 months post stroke ]
   Self-report questionnaire related to confidence in increasing activity and maintaining exercise routines
6. International Physical Activity Questionnaire [ Time Frame: Baseline, within 5 days of last medication dose (8 weeks), at 6 months post stroke ]
   Self-report of activity levels
7. Walking activity, Sensors [ Time Frame: Collected daily for 8 weeks ]
   Daily duration of bouts of walking
8. Walking activity, Sensors [ Time Frame: Collected daily for 8 weeks ]
   Total daily distance walked
9. Walking activity, Sensors [ Time Frame: Collected daily for 8 weeks ]
   Average daily walking speed
10. Walking activity, Sensors [ Time Frame: Collected daily for 8 weeks ]
    Sedentary time
11. Upper extremity practice, Sensors [ Time Frame: Collected daily for 8 weeks ]
    Amount of time practicing
12. Upper extremity practice, Sensors [ Time Frame: Collected daily for 8 weeks ]
    Repetitions of task practice

Eligibility Criteria

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Ages Eligible for Study:	30 Years to 86 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Contacts and Locations

Contacts

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Contact: Bruce Dobkin, MD	310-206-6500	bdobkin@mednet.ucla.edu
Contact: Clarisa Martinez, PT, DPT	310-206-6500	clarisamartinez@mednet.ucla.edu

Locations

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United States, California
California Rehabilitation Institute	Recruiting
Los Angeles, California, United States, 90067
United States, New York
Burke Rehabilitation Center	Not yet recruiting
White Plains, New York, United States, 10605

Sponsors and Collaborators

University of California, Los Angeles

Burke Rehabilitation Hospital

More Information

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Responsible Party:	Bruce H. Dobkin, Principal Investigator, University of California, Los Angeles
ClinicalTrials.gov Identifier:	NCT03172026 History of Changes
Other Study ID Numbers:	IRB#16-001733
First Posted:	May 31, 2017
Last Update Posted:	May 2, 2018
Last Verified:	May 2018

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Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No
Product Manufactured in and Exported from the U.S.:		No

Keywords provided by Bruce H. Dobkin, University of California, Los Angeles:

Telerehabilitation; Maraviroc

Additional relevant MeSH terms:

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Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Maraviroc	HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; CCR5 Receptor Antagonists