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

Официальное название

Maraviroc for Stroke Recovery (MASTER): A Phase 2 Double-Blind Placebo-Controlled Randomized Clinical Trial

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Maraviroc
  Maraviroc (300mg) twice daily for 90 days
• Препарат Mannitol
  Placebo intervention

Первичные конечные точки

• Upper Extremity Fugl-Meyer Assessment (FMA-UE) Score [Срок оценки: Day 90]

Вторичные конечные точки (3)

• Motor Learning Score [Срок оценки: Day 0, 90]
• Number of adverse events (AE) of special interest [Срок оценки: Day 0-180 (inclusive)]
• Number of Serious Adverse Events (SAE) [Срок оценки: 0-180 days (inclusive)]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Швейцария · 1 центр

• Geneva University Hospital — Geneva

Публикации

• 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
• Sharif A, Jeffers MS, Fergusson DA, Bapuji R, Nicholls SG, Humphrey J, Johnston W, Mitchell E, Speirs MA, Stronghill L, Vuckovic M, Wulf S, Shorr R, Dowlatshahi D, Corbett D, Lalu MM. Preclinical systematic review of CCR5 antagonists as cerebroprotective and stroke recovery enhancing agents. Elife. 2025 Apr 7;14:RP103245. doi: 10.7554/eLife.103245. PMID 40193175
• Broc N, Byczynski G, Dirren E, Carrera E. Maraviroc for Stroke Recovery (MASTER): protocol for a phase 2 double-blind placebo-controlled randomised clinical trial. BMJ Open. 2026 May 3;16(4):e109554. doi: 10.1136/bmjopen-2025-109554. PMID 42082248

Идентификаторы

NCT: NCT07080567 · 2024-02359 · 215285

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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