Maraviroc + Exercise for Stroke Recovery

(CAMAROS Trial)

Recruiting at 8 trial locations

Overseen By Alexandra McKinnon

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Calgary

Must not be taking: Anticonvulsants, Antifungals, Antibiotics, Paxlovid

Disqualifiers: Dementia, Renal insufficiency, Cancer, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 8 weeks

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining the drug Maraviroc, which blocks proteins involved in inflammation, with exercise can improve stroke recovery. Participants will receive either Maraviroc or a placebo ("sugar pill") while participating in an eight-week exercise program. The trial seeks individuals who have experienced a stroke in the last eight weeks, have difficulty moving an arm or leg, and are undergoing rehabilitation. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

You may need to stop taking certain medications to participate in this trial. Specifically, if you are currently taking anticonvulsants like Carbamazepine, Phenobarbital, or Phenytoin, or certain antifungal and antibacterial medications like Ketoconazole or Clarithromycin, you will need to stop. Also, if you are taking St. John's Wort or Paxlovid, you will need to discontinue those as well.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that Maraviroc is generally safe for use. In earlier studies, participants taking 300 mg of Maraviroc daily did not encounter major safety issues, indicating that the treatment is mostly safe. Some research even suggests that Maraviroc might aid in improving movement and recovery after a stroke.

While side effects could occur, available information indicates that Maraviroc is safe enough for testing in clinical trials like this one. Prospective participants should know that researchers have already gathered safety information from past studies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for stroke recovery?

Most treatments for stroke recovery focus on physical therapy and medications that aid in neuroplasticity. However, maraviroc is unique because it targets CCR5 receptors, which are involved in the brain's response to injury. This new mechanism of action could potentially enhance neural repair and improve motor recovery more effectively than current options. Researchers are excited about maraviroc's potential to accelerate and improve recovery outcomes for stroke survivors, offering a novel approach to rehabilitation.

What evidence suggests that this trial's treatments could be effective for stroke recovery?

Research has shown that Maraviroc, a type of medication, can aid stroke recovery. By blocking certain activities in the brain, Maraviroc improves movement and recovery after a stroke. In this trial, participants will receive either Maraviroc or a placebo. Some studies found that people taking Maraviroc experienced more significant improvements in stroke severity compared to those taking a placebo. Additionally, combining Maraviroc with exercise has been linked to better movement and thinking abilities. These findings suggest that Maraviroc could be a promising option for enhancing stroke recovery. ^{1 2 3 4 6}

Who Is on the Research Team?

Bruce Dobkin, MD

Principal Investigator

University of California, Los Angeles, California, USA

Sean Dukelow, MD PhD FRCPC

Principal Investigator

University of Calgary, Calgary, Alberta, Canada

Are You a Good Fit for This Trial?

Adults over 18 with hemiparesis from a recent stroke needing inpatient rehab can join. They must have some arm or leg movement, had an ischemic stroke in the brain's anterior part, and be within 6 weeks post-stroke. Participants need support for daily practice and transport. Exclusions include pre-stroke disability, dementia, certain chronic illnesses including hepatitis or cancer, pregnancy, HIV positivity, specific medication use (e.g., anticonvulsants), and severe kidney issues.

Inclusion Criteria

I can move my shoulder slightly and extend fingers without gravity.

I am receiving inpatient rehab for weakness on one side of my body.

I had a stroke between 5 days and 6 weeks ago.

Exclusion Criteria

Pregnant, breastfeeding, or positive test for pregnancy at baseline

You have been diagnosed with HIV.

My kidney function is reduced with a creatinine clearance rate below 60 mL/min.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo baseline physical and cognitive assessments, including the use of wrist and ankle activity sensors

1 week

1 visit (in-person)

Treatment

Participants receive either Maraviroc or placebo alongside an 8-week daily exercise program

8 weeks

4 visits (in-person) for assessments at 4 and 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 6 months post-stroke

4 months

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Activity Sensor
• Exercise Program
• Maraviroc
• Motor Learning
• Placebo

Trial Overview The CAMAROS trial is testing if Maraviroc (a drug blocking CCR5) combined with exercise helps recovery of arm and leg functions after a stroke compared to placebo. It's randomized: participants are put into groups by chance to receive either Maraviroc or a dummy pill alongside their exercises.

How Is the Trial Designed?

Group I: Maraviroc (Celsentri) Experimental Treatment 4 Interventions

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).

Group II: Placebo Placebo Group 4 Interventions

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).

Maraviroc is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Selzentry for:

• HIV-1 infection in combination with other antiretroviral agents

Approved in European Union as Celsentri for:

• HIV-1 infection in combination with other antiretroviral agents

Approved in Canada as Selzentry for:

• HIV-1 infection in combination with other antiretroviral agents

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Parkwood Hospital, London, Ontario

Collaborator

Trials

8

Recruited

790+

Riverview Health Centre Foundation

Collaborator

Trials

6

Recruited

340+

Memorial University of Newfoundland

Collaborator

Trials

73

Recruited

1,836,000+

Dalhousie University

Collaborator

Trials

177

Recruited

402,000+

The Dr. Miriam and Sheldon G. Adelson Medical Research Foundation

Collaborator

Trials

1

Recruited

120+

University Health Network, Toronto

Collaborator

Trials

1,555

Recruited

526,000+

University of California, Los Angeles

Collaborator

Trials

1,594

Recruited

10,430,000+

Sunnybrook Health Sciences Centre

Collaborator

Trials

693

Recruited

1,569,000+

University of British Columbia

Collaborator

Trials

1,506

Recruited

2,528,000+

Published Research Related to This Trial

In an observational study of 58 stroke patients, it was found that they spent only 5.2% of their day with therapists, indicating a lack of sufficient rehabilitation therapy during the acute phase post-stroke.

Most patients received minimal therapy, averaging only 24 minutes of physiotherapy and 23 minutes of occupational therapy, which suggests that current rehabilitation practices may not be adequate to promote recovery in the early stages after a stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Little therapy, little physical activity: rehabilitation within the first 14 days of organized stroke unit care. Bernhardt, J., Chan, J., Nicola, I., et al.[2022]

Only one small randomized controlled trial met the criteria for evaluating vinpocetine's effects on stroke, and it found no significant differences in mortality or dependency between the treatment and placebo groups.

No adverse effects were reported in the study, but the limited evidence means we cannot conclusively determine vinpocetine's efficacy in reducing case fatality or dependency after an acute stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of vinpocetine therapy in acute ischaemic stroke. Bereczki, D., Fekete, I.[2019]

The SMART Toolbox was developed through an international consensus involving 55 experts and stakeholders to standardize outcome measures for arm rehabilitation in stroke patients, ensuring that the selected measures reflect the priorities of stroke survivors, carers, and clinicians.

The toolbox includes 14 key measures, such as the Action Research Arm Test and Fugl-Meyer Assessment, which will enhance data consistency across studies and improve the ability to analyze the efficacy of rehabilitation interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

International consensus recommendations for outcome measurement in post-stroke arm rehabilitation trials. Duncan Millar, J., VAN Wijck, F., Pollock, A., et al.[2021]

In a study of 95 patients with acute carotid ischemic stroke, those who received cereton in addition to traditional treatment showed a significant reduction in neurological deficits and improved functional independence compared to those who only received traditional treatment.

The cost-effectiveness analysis indicated that cereton was more effective, as it achieved better outcomes at a lower cost per improvement in neurological and functional scores than traditional treatment alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of cereton in acute ischemic stroke: results of the trial SOLNTSE]. Kamchatnov, PR., Abusueva, BA., Evzel'man, MA., et al.[2016]

Cervene (nalmefene) was found to be safe and well-tolerated in a randomized trial involving 44 patients treated within 6 hours of an acute ischemic stroke, with no deaths or serious adverse events linked to the drug.

Patients treated with Cervene showed a significantly higher rate of major improvement in stroke severity (66% vs. 33% for placebo) and better recovery outcomes at 3 months (73% vs. 50% for placebo), suggesting potential efficacy in stroke treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized trial of Cervene, a kappa receptor-selective opioid antagonist, in acute ischemic stroke. Clark, WM., Coull, BM., Karukin, M., et al.[2019]

A home-based exercise program for stroke survivors, conducted over 8 weeks with 20 participants, showed significant improvements in motor function and balance compared to usual care, particularly in lower extremity function and gait velocity.

The study confirmed that implementing a randomized controlled trial for post-stroke exercise is feasible, although the effects on upper extremity function and overall health status were less clear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, controlled pilot study of a home-based exercise program for individuals with mild and moderate stroke. Duncan, P., Richards, L., Wallace, D., et al.[2022]

In a study of 99,753 patients with ischemic stroke and 8,824 with intracerebral hemorrhage, early rehabilitation (VER) was widely applied, especially physical therapy, but there was an undersupply of occupational and speech therapy.

Despite the general acceptance of VER's benefits, the findings suggest that severely disabled patients received high-frequency VER, which may contradict recent evidence indicating potential harm for this group, highlighting a need for more cautious application of early rehabilitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Access, timing and frequency of very early stroke rehabilitation - insights from the Baden-Wuerttemberg stroke registry. Reuter, B., Gumbinger, C., Sauer, T., et al.[2018]

This study aims to determine the maximum safe and tolerable intensity of cardiorespiratory fitness (CRF) training for stroke survivors, focusing on participants recruited within one month post-stroke and stratified by their exercise capacity.

The trial will involve 12 interval-based training sessions over four weeks, with intensity adjustments based on the occurrence of dose-limiting events, such as pain or inability to perform usual activities, ensuring safety during early post-stroke rehabilitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determining Maximal Tolerable Aerobic Training Intensity in the Acute Phase after Stroke: a Novel Dose Ranging Trial Protocol. Kramer, SF., Cumming, T., Johnson, L., et al.[2022]

In a study of 1920 stroke patients, including 1520 with ischemic stroke (IS) and 400 with hemorrhagic stroke (HS), certain medications showed significant efficacy in functional rehabilitation, particularly actovegin, instenon, berlition, rheopolyglucin, and gliatilin for IS patients.

Actovegin was the only medication that demonstrated a beneficial effect on rehabilitation for patients with hemorrhagic stroke, highlighting its potential as a key treatment option in post-stroke recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Drug rehabilitation in stroke patients]. Skoromets, AA., Koval'chuk, VV.[2016]

Stroke patients can continue to benefit from physical, occupational, and speech therapy for several months post-event, and self-directed therapy may also be advantageous.

OnabotulinumtoxinA is effective in treating arm spasticity after stroke, and managing depression with selective serotonin reuptake inhibitors can improve both mood and motor recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stroke: posthospital management and recurrence prevention. Silver, B., Wulf Silver, R.[2016]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03172026

Maraviroc to Augment Rehabilitation Outcomes After Stroke Usual post-stroke care plus placebo will be compared to Maraviroc given for 8 weeks in 60 participants (up to 66 to account for dropouts). The primary outcome ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11155100/

Blocking CCR5 activity by maraviroc augmentation in post ... Our proof-of-concept study suggests that a daily dosage of 300 mg of Maraviroc may represent a well-tolerated and potentially effective pharmacological ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04789616

Study Details | NCT04789616 | The Canadian Maraviroc ... After stroke, the combination of progressive skills practice in an adequate dose plus exercise for fitness augments motor and cognitive outcomes.

4. elifesciences.org elifesciences.org/reviewed-preprints/103245

CCR5 antagonists as cerebroprotective and stroke ... observed that CCR5 antagonist (maraviroc) administration one-hour following stroke resulted in greater motor performance on the corner test, ...

5. withpower.com withpower.com/trial/phase-3-stroke-4-2021-eec5e

Maraviroc + Exercise for Stroke Recovery (CAMAROS Trial) Patients treated with Cervene showed a significantly higher rate of major improvement in stroke severity (66% vs. 33% for placebo) and better recovery outcomes ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38844862/

Blocking CCR5 activity by maraviroc augmentation in post- ... Abstract · Background: Post-stroke depression (PSD) is a significant impediment to successful rehabilitation and recovery after a stroke.