Clinical trial NCT04789616: The Canadian Maraviroc Randomized Controlled Trial To Augment Rehabilitation Outcomes After Stroke
Official title: The CAMAROS Trial: The Canadian Maraviroc Randomized Controlled Trial To Augment Rehabilitation Outcomes After Stroke
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Stroke
Keywords: Rehabilitation
Exercise
Maraviroc
Randomized Control Trial
Activity Sensors
Motor Learning
Retention
Wearable Sensors
Celsentri
Lead sponsor: University of Calgary
Sponsor class: OTHER
Collaborators: name: University Health Network, Toronto
name: University of California, Los Angeles
name: Sunnybrook Health Sciences Centre
name: University of British Columbia
name: Memorial University of Newfoundland
name: Dalhousie University
name: Parkwood Hospital, London, Ontario
name: Riverview Health Centre Foundation
name: The Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
First posted: 2021-03-09
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The CAMAROS trial is a randomized controlled phase II trial analyzing the effect of coupling a C-C chemokine receptor 5 (CCR5) antagonist, Maraviroc (Celsentri), and exercise to improve both upper and lower extremity recovery after a stroke.

Detailed description: After stroke, the combination of progressive skills practice in an adequate dose plus exercise for fitness augments motor and cognitive outcomes. However, sensorimotor and cognitive improvements often plateau after 12 weeks. There is an urgent need to find novel methods to drive recovery and lessen limb paralysis. 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, may augment skills learning during rehabilitation training especially during the first three months after onset, by acting on unique molecular components for novel learning.

The CAMAROS trial is a randomized, placebo-controlled, blinded phase II trial evaluating the efficacy of coupling Maraviroc (Celsentri) with exercise rehabilitation across multiple Canadian sites in 120 stroke participants. Patients will begin their participation within 8 weeks of stroke onset. Both groups will receive an exercise program in addition to standard of care rehabilitation, but only one group (the intervention group) will receive the active drug Maraviroc.

Study participants will be evaluated using physical assessments, cognitive assessments, and using wrist and ankle activity sensors at baseline, after 4 weeks of taking the drug/placebo, after 8 weeks of taking the drug/placebo, and at 6-months post-stroke. While enrolled in the study, participants will be required to take part in an 8 week, daily exercise program. Participants will also perform a short motor learning assessment at each formal assessment and again within 72 hours of each formal assessment (initial test and retention test).

Evaluators and participants will be blind to the treatment administered. The trial is constructed with randomization to remove selection and allocation biases and to ensure greater validity in observed differences in the outcome measures.

Eligibility criteria: Inclusion Criteria:

1. Primary ischemic anterior circulation stroke
2. Age ≥18 years
3. At least 5 days after stroke but within 8 weeks of stroke on the date of medication (maraviroc or placebo) start
4. Hemiparesis requiring inpatient rehabilitation
5. Assistance available for daily rehabilitation training practice and for transportation when needed
6. Adequate language skills to understand the Informed Consent and retain information during daily therapies
7. At least one of the following:

   * some shoulder abduction with gravity eliminated and visible extension in two or more digits OR
   * visible hip flexion or extension

Subgroup Stratification Criteria

1. For Upper Extremity Group:

   * Minimum Ability: Medical Research Council (MRC) grade \>1 for shoulder abduction AND MRC grade \>1 for finger extensor on at least two digits
   * Maximum Ability: Upper Extremity Fugl-Meyer Assessment Score \>56
2. For Lower Extremity Group:

   * Minimum Ability: requiring a 2-person assist
   * Maximum Ability: walking speed \<0.8m/s

Exclusion Criteria:

1. Pre-stroke modified Rankin score ≥ 2
2. Limited resources or illness that will not enable a return to living outside of a facility
3. History of dementia
4. History of hepatitis or elevated hepatic transaminases or bilirubin
5. History of renal insufficiency or creatinine clearance (eGFR) \< 60mL / min / 1.73m2
6. Cancer or other chronic illness that makes 1-year survival unlikely or will detract from the ability to carry out exercise and skills practice
7. Existing pre-stroke serious disabling disease (e.g., Parkinson's disease, severe traumatic brain injury, amputation)
8. Seizure related to stroke
9. Acute or chronic epilepsy
10. Currently taking any of the following anticonvulsant medications:

    * Carbamazepine
    * Phenobarbital
    * Phenytoin
11. Pregnant, breastfeeding, or positive test for pregnancy at baseline
12. Women of childbearing potential who are not using one highly effective form of contraception or two forms of effective contraception
13. Known HIV positivity
14. Currently taking any of the following antifungal and/or antibacterial medications:

    * Ketoconazole
    * Itraconazole
    * Voriconazole
    * Rifampin
    * Clarithromycin
    * Rifabutin + Protease Inhibitor
15. Currently taking St. John's Wort
16. Currently taking Paxlovid

Primary outcomes:
measure: Change in Fugl-Meyer Upper Extremity Assessment Score
timeFrame: Baseline (between 5 days and 8 weeks after stroke), after 4 weeks on drug/placebo, after 8 weeks on drug/placebo, and 6-months post-stroke
measure: Change in 10-Meter Walk Test Score
timeFrame: Baseline (between 5 days and 8 weeks after stroke), after 4 weeks on drug/placebo, after 8 weeks on drug/placebo, and 6-months post-stroke
Secondary outcomes:
measure: Action Research Arm Test (ARAT)
timeFrame: Baseline (between 5 days and 8 weeks after stroke), after 4 weeks on drug/placebo, after 8 weeks on drug/placebo, and 6-months post-stroke
measure: 6 Minute Walk Test
timeFrame: Baseline (between 5 days and 8 weeks after stroke), after 4 weeks on drug/placebo, after 8 weeks on drug/placebo, and 6-months post-stroke
Other outcomes:
measure: Fugl-Meyer Lower Extremity Assessment Score
timeFrame: Baseline (between 5 days and 8 weeks after stroke), after 4 weeks on drug/placebo, after 8 weeks on drug/placebo, and 6-months post-stroke
measure: Patient Health Questionnaire 9 (PHQ-9)
timeFrame: Baseline (between 5 days and 8 weeks after stroke), after 8 weeks on drug/placebo, and 6-months post-stroke
measure: Stroke Aphasia Depression Questionnaire (SADQ)
timeFrame: BaselineBaseline (between 5 days and 8 weeks after stroke), after 8 weeks on drug/placebo, and 6-months post-stroke, 8-week assessment, and 6-month assessment
measure: European Quality of Life Across 5 Domains (EQ-5D)
timeFrame: Baseline (between 5 days and 8 weeks after stroke), after 8 weeks on drug/placebo, and 6-months post-stroke
measure: Stroke Impact Scale (SIS)
timeFrame: Baseline (between 5 days and 8 weeks after stroke), after 8 weeks on drug/placebo, and 6-months post-stroke
measure: National Institutes of Health Stroke Scale (NIHSS)
timeFrame: Baseline (between 5 days and 8 weeks after stroke) and 6-months post-stroke
measure: Montreal Cognitive Assessment (MoCA)
timeFrame: Baseline (between 5 days and 8 weeks after stroke) and 6-months post-stroke
Locations:
city: Calgary
country: Canada
facility: University of Calgary & Foothills Medical Centre
state: Alberta
city: Vancouver
country: Canada
facility: University of British Columbia & GF Strong Rehabilitation Centre
state: British Columbia
city: Halifax
country: Canada
facility: Dalhousie University
state: Nova Scotia
city: London
country: Canada
facility: Parkwood Institute
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Toronto Rehabilitation Institute - University Health Network
state: Ontario
Study officials:
affiliation: University of Calgary, Calgary, Alberta, Canada
name: Sean Dukelow, MD PhD FRCPC
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Los Angeles, California, USA
name: Bruce Dobkin, MD
role: STUDY_CHAIR
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