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

Trial Summary

What is the purpose of this trial?

This trial is testing whether the drug Maraviroc, combined with exercise, can help stroke patients recover better. It targets patients shortly after their stroke because recovery often slows down after a few months. Maraviroc might help the brain and nerves heal more effectively when paired with exercise.

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.

What data supports the effectiveness of the treatment Maraviroc + Exercise for Stroke Recovery?

Exercise and physical therapy have been shown to be beneficial for stroke recovery, as they can improve motor function and overall rehabilitation. Additionally, the use of selective serotonin reuptake inhibitors (a type of antidepressant) has been associated with improved motor recovery, suggesting that pharmacological interventions can aid in stroke rehabilitation. ^{1 2 3 4 5}

How is the drug Maraviroc combined with exercise unique for stroke recovery?

Maraviroc, typically used for HIV treatment, is being explored for stroke recovery due to its potential to reduce inflammation and improve brain repair, which is different from standard stroke treatments that focus on blood flow restoration and physical rehabilitation. ^{6 7 8 9 10}

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

Eligibility Criteria

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 18 years old or older.

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

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

A systematic review of vinpocetine therapy in acute ischaemic stroke. [2019]

2. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Efficacy of cereton in acute ischemic stroke: results of the trial SOLNTSE]. [2016]

3. United States pubmed.ncbi.nlm.nih.gov

Randomized trial of Cervene, a kappa receptor-selective opioid antagonist, in acute ischemic stroke. [2019]

4. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Drug rehabilitation in stroke patients]. [2016]

5. United States pubmed.ncbi.nlm.nih.gov

Stroke: posthospital management and recurrence prevention. [2016]

6. United States pubmed.ncbi.nlm.nih.gov

A randomized, controlled pilot study of a home-based exercise program for individuals with mild and moderate stroke. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Access, timing and frequency of very early stroke rehabilitation - insights from the Baden-Wuerttemberg stroke registry. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Determining Maximal Tolerable Aerobic Training Intensity in the Acute Phase after Stroke: a Novel Dose Ranging Trial Protocol. [2022]

9. Sweden pubmed.ncbi.nlm.nih.gov

Little therapy, little physical activity: rehabilitation within the first 14 days of organized stroke unit care. [2022]

10. Italy pubmed.ncbi.nlm.nih.gov

International consensus recommendations for outcome measurement in post-stroke arm rehabilitation trials. [2021]