MINocyclinE to Reduce inflammation and blood brain barrier leakage in small Vessel diseAse (MINERVA) trial study protocol.
MINocyclinE to Reduce inflammation and blood brain barrier leakage in small Vessel diseAse (MINERVA) trial study protocol.
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DOI：
10.1177/23969873221100338
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发表时间：
2022-09
影响因子：
6.1
通讯作者：
Markus, Hugh S.
中科院分区：
文献类型：
--
作者：
Brown, Robin B.;Tozer, Daniel J.;Loubiere, Laurence;Hong, Young T.;Fryer, Tim D.;Williams, Guy B.;Graves, Martin J.;Aigbirhio, Franklin, I;O'Brien, John T.;Markus, Hugh S.
关键词：
脑小血管病（SVD）是中风和认知障碍的常见原因。最近的数据表明，神经炎症和血脑屏障（BBB）通透性增加在其发病机制，但这些过程是否是因果关系，并可以治疗修改是不确定的。在SVD的啮齿动物模型中，米诺环素与减少的白色病变、炎症和BBB通透性相关。确定是否可以在SVD中改变血脑屏障通透性（使用动态对比增强MRI测量）和小胶质细胞活化（使用放射性配体11 C-PK 11195通过正电子发射断层扫描测量）。一项在44例中重度SVD（定义为临床腔隙性卒中和融合性白色高信号）受试者中进行的米诺环素100 mg每日两次治疗3个月的II期、随机、双盲、安慰剂对照试验。主要结局指标是使用PET-MRI成像确定的血脑屏障通透性和小胶质细胞活化的局灶性增加的体积和强度。次要结局指标包括血清中的炎症生物标志物，以及1年随访期间常规MRI标志物和认知表现的变化。MINERVA试验旨在测试米诺环素是否可以影响被认为参与SVD进展的新病理过程，并将提供关于SVD中中枢神经系统炎症是否可以治疗调节的见解。
Cerebral small vessel disease (SVD) is a common cause of stroke and cognitive impairment. Recent data has implicated neuroinflammation and increased blood-brain barrier (BBB) permeability in its pathogenesis, but whether such processes are causal and can be therapeutically modified is uncertain. In a rodent model of SVD, minocycline was associated with reduced white matter lesions, inflammation and BBB permeability. To determine whether blood-brain barrier permeability (measured using dynamic contrast-enhanced MRI) and microglial activation (measured by positron emission tomography using the radioligand 11C-PK11195) can be modified in SVD. Phase II randomised double blind, placebo-controlled trial of minocycline 100 mg twice daily for 3 months in 44 participants with moderate to severe SVD defined as a clinical lacunar stroke and confluent white matter hyperintensities. Primary outcome measures are volume and intensity of focal increases of blood-brain barrier permeability and microglial activation determined using PET-MRI imaging. Secondary outcome measures include inflammatory biomarkers in serum, and change in conventional MRI markers and cognitive performance over 1 year follow up. The MINERVA trial aims to test whether minocycline can influence novel pathological processes thought to be involved in SVD progression, and will provide insights into whether central nervous system inflammation in SVD can be therapeutically modulated.
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影响因子：
3.3
作者：
Taheri S;Gasparovic C;Shah NJ;Rosenberg GA
通讯作者：
Rosenberg GA
DOI：
10.1093/brain/awab003
发表时间：
2021-06-22
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Walsh J;Tozer DJ;Sari H;Hong YT;Drazyk A;Williams G;Shah NJ;O'Brien JT;Aigbirhio FI;Rosenberg G;Fryer TD;Markus HS
通讯作者：
Markus HS
影响因子：
8.3
作者：
Marstrand, JR;Garde, E;Larsson, HBW
通讯作者：
Larsson, HBW
影响因子：
10.6
作者：
Burgos, Ninon;Cardoso, M. Jorge;Ourselin, Sebastien
通讯作者：
Ourselin, Sebastien
影响因子：
3.7
作者：
Bader, Stefanie;Wolf, Luisa;Wetzel, Christian H.
通讯作者：
Wetzel, Christian H.