The Canadian Maraviroc Randomized Controlled Trial To Augment Rehabilitation Outcomes After Stroke

NCT04789616 | Recruiting Phase 2 DMC

• 1 other identifier: REB21-0258
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 6

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.

Conditions

Stroke

Keywords

Rehabilitation; Exercise; Maraviroc; Randomized Control Trial; Activity Sensors; Motor Learning; Retention; Wearable Sensors; Celsentri

Outcome Measures

Primary Outcomes (2)

• Change in Fugl-Meyer Upper Extremity Assessment Score

  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.

  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

• Change in 10-Meter Walk Test Score

  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.

  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 (2)

• Action Research Arm Test (ARAT)

  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

• 6 Minute Walk Test

  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 (7)

• Fugl-Meyer Lower Extremity Assessment Score

  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

• Patient Health Questionnaire 9 (PHQ-9)

  Baseline (between 5 days and 8 weeks after stroke), after 8 weeks on drug/placebo, and 6-months post-stroke

• Stroke Aphasia Depression Questionnaire (SADQ)

  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

Study Arms (2)

Maraviroc (Celsentri)

EXPERIMENTAL

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; Behavioral: Exercise Program; Device: Activity Sensor; Behavioral: Motor Learning

Placebo

PLACEBO COMPARATOR

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; Device: Activity Sensor; Behavioral: Motor Learning

Interventions

Maraviroc DRUG

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

Also known as: Celsentri

Maraviroc (Celsentri)

Exercise Program BEHAVIORAL

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 physiotherapy \& occupational therapy) 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.

Maraviroc (Celsentri); Placebo

Placebo OTHER

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

Also known as: "Sugar" Pill

Placebo

Activity Sensor DEVICE

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.

Maraviroc (Celsentri); Placebo

Motor Learning BEHAVIORAL

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 72 hours of the initial assessment (initial test and retention test).

Maraviroc (Celsentri); Placebo

Eligibility Criteria

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

You may qualify if:

• Primary ischemic anterior circulation stroke
• Age ≥18 years
• At least 5 days after stroke but within 8 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: 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
• For Lower Extremity Group:
• Minimum Ability: requiring a 2-person assist

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (6)

University of Calgary & Foothills Medical Centre

Calgary, Alberta, T2N 2T9, Canada

RECRUITING

University of British Columbia & GF Strong Rehabilitation Centre

Vancouver, British Columbia, V5Z 2G9, Canada

RECRUITING

Dalhousie University

Halifax, Nova Scotia, B3H 3J5, Canada

RECRUITING

Parkwood Institute

London, Ontario, N6C 0A7, Canada

RECRUITING

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

NOT YET RECRUITING

Toronto Rehabilitation Institute - University Health Network

Toronto, Ontario, M5G 2A2, Canada

NOT YET RECRUITING

Related Publications (9)

• Ben Assayag E, Korczyn AD, Giladi N, Goldbourt U, Berliner AS, Shenhar-Tsarfaty S, Kliper E, Hallevi H, Shopin L, Hendler T, Baashat DB, Aizenstein O, Soreq H, Katz N, Solomon Z, Mike A, Usher S, Hausdorff JM, Auriel E, Shapira I, Bornstein NM. Predictors for poststroke outcomes: the Tel Aviv Brain Acute Stroke Cohort (TABASCO) study protocol. Int J Stroke. 2012 Jun;7(4):341-7. doi: 10.1111/j.1747-4949.2011.00652.x. Epub 2011 Nov 2.

  PMID: 22044517 BACKGROUND

• Ben Assayag E, Shenhar-Tsarfaty S, Korczyn AD, Kliper E, Hallevi H, Shopin L, Auriel E, Giladi N, Mike A, Halevy A, Weiss A, Mirelman A, Bornstein NM, Hausdorff JM. Gait measures as predictors of poststroke cognitive function: evidence from the TABASCO study. Stroke. 2015 Apr;46(4):1077-83. doi: 10.1161/STROKEAHA.114.007346. Epub 2015 Feb 12.

  PMID: 25677599 BACKGROUND

• Ben Assayag E, Tene O, Korczyn AD, Shopin L, Auriel E, Molad J, Hallevi H, Kirschbaum C, Bornstein NM, Shenhar-Tsarfaty S, Kliper E, Stalder T. High hair cortisol concentrations predict worse cognitive outcome after stroke: Results from the TABASCO prospective cohort study. Psychoneuroendocrinology. 2017 Aug;82:133-139. doi: 10.1016/j.psyneuen.2017.05.013. Epub 2017 May 18.

  PMID: 28549269 BACKGROUND

• Dobkin BH. A Rehabilitation-Internet-of-Things in the Home to Augment Motor Skills and Exercise Training. Neurorehabil Neural Repair. 2017 Mar;31(3):217-227. doi: 10.1177/1545968316680490. Epub 2016 Nov 24.

  PMID: 27885161 BACKGROUND

• Duncan PW, Sullivan KJ, Behrman AL, Azen SP, Wu SS, Nadeau SE, Dobkin BH, Rose DK, Tilson JK, Cen S, Hayden SK; LEAPS Investigative Team. Body-weight-supported treadmill rehabilitation after stroke. N Engl J Med. 2011 May 26;364(21):2026-36. doi: 10.1056/NEJMoa1010790.

  PMID: 21612471 BACKGROUND

• Hiragami S, Inoue Y, Harada K. Minimal clinically important difference for the Fugl-Meyer assessment of the upper extremity in convalescent stroke patients with moderate to severe hemiparesis. J Phys Ther Sci. 2019 Nov;31(11):917-921. doi: 10.1589/jpts.31.917. Epub 2019 Nov 26.

  PMID: 31871377 BACKGROUND

• Joy MT, Ben Assayag E, Shabashov-Stone D, Liraz-Zaltsman S, Mazzitelli J, Arenas M, Abduljawad N, Kliper E, Korczyn AD, Thareja NS, Kesner EL, Zhou M, Huang S, Silva TK, Katz N, Bornstein NM, Silva AJ, Shohami E, Carmichael ST. CCR5 Is a Therapeutic Target for Recovery after Stroke and Traumatic Brain Injury. Cell. 2019 Feb 21;176(5):1143-1157.e13. doi: 10.1016/j.cell.2019.01.044.

  PMID: 30794775 BACKGROUND

• Lohse K, Bland MD, Lang CE. Quantifying Change During Outpatient Stroke Rehabilitation: A Retrospective Regression Analysis. Arch Phys Med Rehabil. 2016 Sep;97(9):1423-1430.e1. doi: 10.1016/j.apmr.2016.03.021. Epub 2016 Apr 22.

  PMID: 27109329 BACKGROUND

• Zhou M, Greenhill S, Huang S, Silva TK, Sano Y, Wu S, Cai Y, Nagaoka Y, Sehgal M, Cai DJ, Lee YS, Fox K, Silva AJ. CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory. Elife. 2016 Dec 20;5:e20985. doi: 10.7554/eLife.20985.

  PMID: 27996938 BACKGROUND

Related Links

• Product Monograph for Celsentri (Maraviroc)

MeSH Terms

Conditions

Stroke; Motor Activity

Interventions

Maraviroc; Resistance Training; Sugars

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Physical Therapy Modalities; Physical Conditioning, Human; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Carbohydrates

Study Officials

• Sean Dukelow, MD PhD FRCPC

  University of Calgary, Calgary, Alberta, Canada

  PRINCIPAL INVESTIGATOR

• Bruce Dobkin, MD

  University of California, Los Angeles, California, USA

  STUDY CHAIR

Central Study Contacts

Alexandra McKinnon

CONTACT

403-944-4050; alexandra.mckinnon@ucalgary.ca

Mark Piitz

CONTACT

403-944-4050; mapiitz@ucalgary.ca

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: SPONSOR

Study Record Dates

• First Submitted: March 5, 2021
• First Posted: March 9, 2021
• Study Start: September 15, 2022
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: July 9, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (6)