Assayag Einor Ben, Molad Jeremy, Seyman Estelle, Rotschild Ofer, Zeltzer Ehud, Sadeh-Gonik Udi, Bregman Noa, Alpernas Aviva, Segal Yahel, Bashat Dafna Ben, Nathan Talya, Hawwari Muhamad, Tene Oren, Hallevi Hen
Departments of Neurology, Psychiatry and Radiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Faculty of Medicine and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
Eur Stroke J. 2022 Sep;7(3):314-322. doi: 10.1177/23969873221098857. Epub 2022 May 27.
Current evidence suggest that 25%-33% of stroke-survivors develop post-stroke cognitive impairment (PSCI). The licensed drug Maraviroc, a CCR5-antagonist, is postulated to act via a neuroprotective mechanism that may offer the potential of preventing progression to vascular dementia. Our hypothesis: Maraviroc may have the potential to augment learning skills and cognitive performance by affecting synaptic plasticity, along with neuro-inflammatory modulation in patients with cerebral small vessel disease (SVD) and PSCI.
MARCH is a multi-center, double-blind randomized-control Phase-II trial of Maraviroc 150 or 600 mg/day versus placebo for 12-months in five stroke centers in Israel. Included are patients diagnosed with recent (1-24 months) subcortical stroke who experience mild PSCI and have evidence of white matter lesions and SVD on neuroimaging.
Primary outcomes: 1. Change in cognitive scores. 2. Drug related adverse events. Secondary outcomes: change in functional and affective scores, MRI-derived measures, inflammatory markers, carotid atherosclerosis, cerebrospinal-fluid biomarkers in a sub-study. A sample size of 60 in each treatment group and 30 in the placebo group (total - 150 participants) provides 80% power between the treatment and the placebo groups.
The results of this work could lead to a novel, readily available, therapeutic avenue to reduce PSCI, and possibly other pathologies. This study will test safety and effectiveness of Maraviroc in limiting cognitive deterioration and/or post stroke cognitive impairment in patients with cerebral small vessel disease.
First-patient first-visit was May 2021. Recruitment to complete in 2023, follow-up to complete in 2024.
目前的证据表明，25%-33%的中风幸存者会发生中风后认知障碍（PSCI）。已获许可的药物马拉维若，一种CCR5拮抗剂，据推测是通过一种神经保护机制起作用，这种机制可能具有预防进展为血管性痴呆的潜力。我们的假设：马拉维若可能有潜力通过影响突触可塑性以及调节脑小血管疾病（SVD）和PSCI患者的神经炎症来增强学习技能和认知表现。
MARCH是一项多中心、双盲随机对照II期试验，在以色列的五个中风中心对150或600毫克/天的马拉维若与安慰剂进行为期12个月的试验。纳入的患者为近期（1-24个月）被诊断为皮质下中风且患有轻度PSCI，并且在神经影像学上有白质病变和SVD证据的患者。
主要结果：1. 认知评分的变化。2. 与药物相关的不良事件。次要结果：功能和情感评分的变化、MRI衍生指标、炎症标志物、颈动脉粥样硬化、亚组研究中的脑脊液生物标志物。每个治疗组60例样本量以及安慰剂组30例样本量（共150名参与者）可使治疗组与安慰剂组之间的检验效能达到80%。
这项工作的结果可能会带来一种新的、易于获得的治疗途径，以减少PSCI以及可能的其他病症。本研究将测试马拉维若在限制脑小血管疾病患者认知恶化和/或中风后认知障碍方面的安全性和有效性。
首例患者首次就诊时间为2021年5月。招募工作将于2023年完成，随访将于2024年完成。
