CAMAROS: The Canadian Maraviroc RCT To Augment Rehabilitation Outcomes After Stroke

Sponsor

University of Calgary (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04789616

Collaborator

University Health Network, Toronto (Other), University of California, Los Angeles (Other), Sunnybrook Health Sciences Centre (Other), University of British Columbia (Other), Memorial University of Newfoundland (Other), Dalhousie University (Other), Parkwood Hospital, London, Ontario (Other), Riverview Health Centre Foundation (Other), The Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (Other)

120

Enrollment

Locations

Arms

Anticipated Duration (Months)

17.1

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Stroke	Drug: Maraviroc Behavioral: Exercise Program Other: Placebo Device: Activity Sensor Behavioral: Motor Learning	Phase 2

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 6 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 24 hours of each formal assessment (initial test and 24-hour 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

The CAMAROS Trial: The Canadian Maraviroc RCT To Augment Rehabilitation Outcomes After Stroke

Anticipated Study Start Date :

May 1, 2022

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Maraviroc (Celsentri) Maraviroc (Celsentri) will be administered to this group. Participants will be administered a dose of 300mg to be taken twice per day for the duration of the exercise intervention (8 weeks).	Drug: Maraviroc Half of the participants will take maraviroc for a period of 8 weeks. Other Names: Celsentri Behavioral: Exercise Program All participants will take part in an 8-week exercise program. While in-hospital, participants will undergo standard of care rehabilitation (estimated at 45 minutes each daily for PT & OT) plus a supplementary upper extremity exercise program (Graded Repetitive Arm Supplementary Program (GRASP); estimated at 1 hour daily). After discharge from inpatient care, participants will complete an at-home supplementary upper and lower extremity exercise program. This program will include 30 minutes daily walking or sit-to-stand exercises and 30 minutes daily practice using the GRASP program. Device: Activity Sensor Participants will be asked to wear small activity sensors (one on each wrist and one on each ankle, total of four sensors) at the baseline, 4-week, 8-week, and 6-month assessments for 7 consecutive days. Activity related to walking, sleep, physical activity, and arm and leg movement throughout the day will be measured. The sensors will be worn for a total of 28 days throughout the study. Behavioral: Motor Learning Participants will be asked to perform a computer-based motor learning assessment at the baseline, 4-week, 8-week, and 6-month assessments. A retention task, which involves shorter versions of the initial tasks, will also be completed within 24 hours of the initial assessment (initial test and 24-hour retention test).
Placebo Comparator: Placebo An over-encapsulated placebo, or "sugar pill" (so it appears identical to the trial drug) will be administered to this group. Participants will be administered the placebo identical to the 300mg maraviroc tablet for the duration of the exercise intervention (8 weeks).	Behavioral: Exercise Program All participants will take part in an 8-week exercise program. While in-hospital, participants will undergo standard of care rehabilitation (estimated at 45 minutes each daily for PT & OT) plus a supplementary upper extremity exercise program (Graded Repetitive Arm Supplementary Program (GRASP); estimated at 1 hour daily). After discharge from inpatient care, participants will complete an at-home supplementary upper and lower extremity exercise program. This program will include 30 minutes daily walking or sit-to-stand exercises and 30 minutes daily practice using the GRASP program. Other: Placebo Half of the participants will take a placebo for a period of 8 weeks. Other Names: "Sugar" Pill Device: Activity Sensor Participants will be asked to wear small activity sensors (one on each wrist and one on each ankle, total of four sensors) at the baseline, 4-week, 8-week, and 6-month assessments for 7 consecutive days. Activity related to walking, sleep, physical activity, and arm and leg movement throughout the day will be measured. The sensors will be worn for a total of 28 days throughout the study. Behavioral: Motor Learning Participants will be asked to perform a computer-based motor learning assessment at the baseline, 4-week, 8-week, and 6-month assessments. A retention task, which involves shorter versions of the initial tasks, will also be completed within 24 hours of the initial assessment (initial test and 24-hour retention test).

Arm

Intervention/Treatment

Experimental: Maraviroc (Celsentri)

Maraviroc (Celsentri) will be administered to this group. Participants will be administered a dose of 300mg to be taken twice per day for the duration of the exercise intervention (8 weeks).

Drug: Maraviroc

Half of the participants will take maraviroc for a period of 8 weeks.

Other Names:

Celsentri

Behavioral: Exercise Program

All participants will take part in an 8-week exercise program. While in-hospital, participants will undergo standard of care rehabilitation (estimated at 45 minutes each daily for PT & OT) plus a supplementary upper extremity exercise program (Graded Repetitive Arm Supplementary Program (GRASP); estimated at 1 hour daily). After discharge from inpatient care, participants will complete an at-home supplementary upper and lower extremity exercise program. This program will include 30 minutes daily walking or sit-to-stand exercises and 30 minutes daily practice using the GRASP program.

Device: Activity Sensor

Participants will be asked to wear small activity sensors (one on each wrist and one on each ankle, total of four sensors) at the baseline, 4-week, 8-week, and 6-month assessments for 7 consecutive days. Activity related to walking, sleep, physical activity, and arm and leg movement throughout the day will be measured. The sensors will be worn for a total of 28 days throughout the study.

Behavioral: Motor Learning

Participants will be asked to perform a computer-based motor learning assessment at the baseline, 4-week, 8-week, and 6-month assessments. A retention task, which involves shorter versions of the initial tasks, will also be completed within 24 hours of the initial assessment (initial test and 24-hour retention test).

Placebo Comparator: Placebo

An over-encapsulated placebo, or "sugar pill" (so it appears identical to the trial drug) will be administered to this group. Participants will be administered the placebo identical to the 300mg maraviroc tablet for the duration of the exercise intervention (8 weeks).

Behavioral: Exercise Program

Other: Placebo

Half of the participants will take a placebo for a period of 8 weeks.

Other Names:

"Sugar" Pill

Device: Activity Sensor

Behavioral: Motor Learning

Outcome Measures

Primary Outcome Measures

Change in Fugl-Meyer Upper Extremity Assessment Score [Baseline (between 5 days and 6 weeks after stroke), after 4 weeks on drug/placebo, after 8 weeks on drug/placebo, and 6-months post-stroke]
Difference in subscale scores on the Upper-Extremity Fugl-Meyer Assessment - both motor (max 66) and sensory (max 12) components. Higher scores indicate better outcome.
Change in 10-Meter Walk Test Score [Baseline (between 5 days and 6 weeks after stroke), after 4 weeks on drug/placebo, after 8 weeks on drug/placebo, and 6-months post-stroke]
A performance measure used to assess walking speed in meters per second over a short distance. It can be used to determine functional mobility, gait, and vestibular function. Faster speed indicates better function.

Secondary Outcome Measures

Action Research Arm Test (ARAT) [Baseline (between 5 days and 6 weeks after stroke), after 4 weeks on drug/placebo, after 8 weeks on drug/placebo, and 6-months post-stroke]
The ARAT assesses arm function to determine the quality of the arm movement, and the limitation of activity. The ARAT consists of 4 sub-tests; that examines and individual's grip, grasp, pinch and gross motor movement in order to determine upper extremity function. Objects of varying size, shape, and weight must be either grasped, handled or moved in a specific task in order to evaluate function. Low scores mean worse function with the minimum possible score being 0 and the highest possible score being 57 (normal function).
6 Minute Walk Test [Baseline (between 5 days and 6 weeks after stroke), after 4 weeks on drug/placebo, after 8 weeks on drug/placebo, and 6-months post-stroke]
An assessment of ambulatory function by measuring the distance walked over a period of 6 minutes. Greater distance walked indicates better function.

Other Outcome Measures

Fugl-Meyer Lower Extremity Assessment Score [Baseline (between 5 days and 6 weeks after stroke), after 4 weeks on drug/placebo, after 8 weeks on drug/placebo, and 6-months post-stroke]
Fugl-Meyer Lower Extremity Assessment assesses motor and sensorimotor impairment in the lower extremities. Total score is between 0 and 34. Sub-scales include: proximal (0-18), knee/ankle (0-10) and coordination/speed (0-6). Higher scores indicate better performance. Sub-scale scores are summed to calculate total score.
Patient Health Questionnaire 9 (PHQ-9) [Baseline (between 5 days and 6 weeks after stroke), after 8 weeks on drug/placebo, and 6-months post-stroke]
A 9-question measurement used to screen for the presence and severity of depression.
Stroke Aphasia Depression Questionnaire (SADQ) [BaselineBaseline (between 5 days and 6 weeks after stroke), after 8 weeks on drug/placebo, and 6-months post-stroke, 8-week assessment, and 6-month assessment]
A 10-item questionnaire completed by a caregiver to quickly assess depressive symptoms in stroke patients with aphasia. Higher scores indicate a greater likelihood of depression.
European Quality of Life Across 5 Domains (EQ-5D) [Baseline (between 5 days and 6 weeks after stroke), after 8 weeks on drug/placebo, and 6-months post-stroke]
A self-completion questionnaire used to assess health-related quality of life.
Stroke Impact Scale (SIS) [Baseline (between 5 days and 6 weeks after stroke), after 8 weeks on drug/placebo, and 6-months post-stroke]
Stroke-specific, self-report, health status measure. Assesses multiple domains on a 5-point Likert scale. Domains include: strength (4-20), hand function (5-25), activities of daily living/instrumental activities of daily living (10-50), mobility (9-45), communication (7-35), emotion (9-45), memory and thinking (7-35), and participation (8-40). An extra question asks that the patient rate on a scale from 0 - 100 how much they feel that he/she has recovered from his/her stroke. The 4 physical domains (strength, hand function, mobility and activities of daily living) can be summed together to create a single, physical dimension score (28-140) while all other domains should remain separate. Higher scores indicate better function.
National Institutes of Health Stroke Scale (NIHSS) [Baseline (between 5 days and 6 weeks after stroke) and 6-months post-stroke]
A 15-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. Higher scores indicate greater impairment.
Montreal Cognitive Assessment (MoCA) [Baseline (between 5 days and 6 weeks after stroke) and 6-months post-stroke]
A cognitive screening test used to assess: short term memory, visuospatial abilities, executive functions, attention, concentration, working memory, language, and orientation to time and place. Higher scores indicate better function.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

For Upper Extremity Group:

Minimum Ability: MRC grade >1 for shoulder abduction AND MRC grade >1 for finger extensor on at least one digit
Maximum Ability: Upper Extremity Fugl-Meyer Assessment Score >56

For Lower Extremity Group:

Minimum Ability: requiring a 2-person assist
Maximum Ability: walking speed <0.8m/s, no visible hip flexion or extension

Exclusion Criteria:

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

Carbamazepine
Phenobarbital
Phenytoin

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

Ketoconazole
Itraconazole
Voriconazole
Rifampin
Clarithromycin
Rifabutin + Protease Inhibitor

Currently taking St. John's Wort

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of British Columbia & GF Strong Centre	Vancouver	British Columbia	Canada	V5Z 2G9
2	Riverview Health Centre	Winnipeg	Manitoba	Canada	R3L 2P4
3	Memorial University of Newfoundland	Saint John's	Newfoundland and Labrador	Canada	A1A 1E5
4	Dalhousie University	Halifax	Nova Scotia	Canada	B3H 3J5
5	Parkwood Institute	London	Ontario	Canada	N6C 0A7
6	Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada	M4N 3M5
7	Toronto Rehabilitation Institute - University Health Network	Toronto	Ontario	Canada	M5G 2A2

Sponsors and Collaborators

University of Calgary
University Health Network, Toronto
University of California, Los Angeles
Sunnybrook Health Sciences Centre
University of British Columbia
Memorial University of Newfoundland
Dalhousie University
Parkwood Hospital, London, Ontario
Riverview Health Centre Foundation
The Dr. Miriam and Sheldon G. Adelson Medical Research Foundation

Investigators

Principal Investigator: Sean Dukelow, MD PhD FRCPC, University of Calgary, Calgary, Alberta, Canada
Study Chair: Bruce Dobkin, MD, University of California, Los Angeles, California, USA