Manipulating the Peri-Infarct Area Using Maraviroc to Enhance Motor Skills After Stroke (MASTER)

Emmanuel Carrera

Status and phase: Enrolling; Phase 2

Conditions: Ischemic Stroke; Stroke; Stroke Acute

Treatments: Drug: Mannitol; Drug: Maraviroc

Study type: Interventional

Funder types: Other

Identifiers

NCT07080567

2024-02359

215285 (Other Grant/Funding Number)

Details and patient eligibility

About

MASTER is a single-center, patient and investigator-blinded, Randomized Controlled Trial (RCT) to compare the efficacy of Maraviroc, a C-C chemokine receptor 5 (CCR5) antagonist, against placebo regarding motor function and motor learning skills in the first 3 months after ischemic stroke.

Full description

Stroke is a common disease and one of the leading causes of death and disability worldwide. Despite advances in acute stroke therapies (intravenous thrombolysis and/or mechanical thrombectomy), deficits remain frequent after stroke. Pharmacological approaches have the benefit of being independent of patient participation, are easily administered, and involve limited medical resources. Unfortunately, the efficacy of several drugs that improve behavioural in preclinical models have yet to be confirmed in humans. Maraviroc, a C-C chemokine receptor 5 (CCR5) antagonist has shown promise in preclinical models, and instead of targeting neurotransmitters, is believed to augment rehabilitation by decreasing infarct size, increasing neuroplasticity, and most importantly, improving behaviour.

The MASTER trial is a single-center, double-blinded, randomized placebo-controlled, phase II clinical trial designed to evaluate the efficacy of Maraviroc (Celsentri) compared to a placebo, in improving outcomes following ischemic stroke in the early stage of recovery. 80 patients will be recruited within 5 days of stroke onset, and will receive either Maraviroc or a placebo drug for 90 days.

Participants will be assessed using a combination of clinical measurements, motor tests, and biometrics throughout the 90 days of intervention, and upon follow-up at 6-months post stroke onset. Several types of brain images will be obtained before and after the intervention period (day 0 and day 90), and participants will also perform a motor learning task before and after the intervention period (day 0 and day 90). Study personnel and participants will be blinded to the treatment, which will be randomly assigned to an intervention group with stratification based on side of the infarct and motor deficit.

Enrollment: 80 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Informed consent as documented by signature
• ≥18 years at time of signing of informed consent
• Acute ischemic stroke.
• Stroke onset < 7 days from randomization.
• Contralateral, unilateral, incomplete upper limb paresis, incl. :
• FMA-UE < 63/66
• Residual voluntary finger extension (VFE) of > 10 degrees

Exclusion criteria

• Pregnancy/lactation or positive pregnancy test in women of childbearing age
• Pre-stroke handicap (mRS > 2)
• Diseases affecting motor function (e.g., Parkinson's Disease, Amyotrophic Lateral Sclerosis (ALS))
• Participation in another study with investigational medicinal product within 30 days preceding and during the present study
• Enrolment of the investigator, his/her family members, employees, or other dependent persons
• Known hypersensitivity to Maraviroc, Mannitol, peanuts, or soy
• History of significant liver disease, hepatitis, elevated liver function tests (> 1.5 upper limit of normal)
• History of significant renal disease or End Stage Renal Disease/dialysis, acute renal injury, Creatinine Clearance (CrCl < 30ml/min/1.73m2)
• Patients with cardiovascular comorbidities and risk for orthostatic hypotension
• HIV infection
• Concomitant use of strong CYP3A4 inhibitors or inducers

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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80 participants in 2 patient groups, including a placebo group

Maraviroc

Active Comparator group

Description:

Maraviroc (Celsentri) 300 mg twice daily

Treatment:

Drug: Maraviroc

Placebo

Placebo Comparator group

Description:

Placebo (Mannitol) encapsulated

Treatment:

Drug: Mannitol