MCLENA-1: A Phase II Clinical Trial for the Assessment of Safety, Tolerability, and Efficacy of Lenalidomide in Patients with Mild Cognitive Impairment Due to Alzheimer's Disease.

IF 1.4 Q4 MEDICINE, RESEARCH & EXPERIMENTAL Open Access Journal of Clinical Trials Pub Date : 2020-01-01 Epub Date: 2020-01-07 DOI:10.2147/oajct.s221914
Boris Decourt, Jeffrey Wilson, Aaron Ritter, Christopher Dardis, Frank P DiFilippo, Xiaowei Zhuang, Dietmar Cordes, Garam Lee, Nadia D Fulkerson, Tessa St Rose, Katurah Hartley, Marwan N Sabbagh
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Abstract

With the general population reaching higher ages, a surge in Alzheimer's disease (AD) incidence will happen in the coming decades, putting a heavy burden on families and healthcare systems Worldwide. This emphasizes the pressing need for AD therapeutic interventions. Accumulating evidence indicates that inflammation is prominent both in the blood and central nervous system of AD sufferers. These data suggest that systemic inflammation plays a crucial role in the cause and effects of AD neuropathology. Capitalizing on our experience from a previous clinical trial with thalidomide, we hypothesize that modulating inflammation via the pleiotropic immunomodulator lenalidomide may alter AD if administered during a proper time window in the course of the disease. Thus, in this Phase II, proof-of mechanism study, 30 amnestic mild cognitive impairment (aMCI) subjects will be treated with lenalidomide at 10 mg/day for 12 months on a 1:1 ratio, followed by a 6 months washout period. The primary objective of this study is to investigate the effect of lenalidomide on cognition, which is assessed at regular intervals. The secondary objective is to assess the safety and tolerability of lenalidomide in aMCI patients evaluated through adverse events, vital signs, clinical biochemistry, and physical and neurological examinations. Tertiary objectives are to analyze the effects of lenalidomide on brain amyloid loads (Florbetapir PET imaging) and neurodegeneration (volumetric MRI) by comparing pre- and post-dosing data. Finally, exploratory objectives will investigate whether blood inflammatory markers can serve as surrogate markers of therapeutic efficacy. Our study should determine whether lenalidomide is safe in AD subjects and whether it can alter the clinical progression of AD when administered before dementia onset. If effective, lenalidomide would become the first drug capable of delaying the trajectory of AD, which could lead the way to find additional, less toxic treatments in the near future.

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MCLENA-1:评估来那度胺对阿尔茨海默病所致轻度认知障碍患者的安全性、耐受性和疗效的 II 期临床试验。
随着总人口年龄的增长,阿尔茨海默病(AD)的发病率将在未来几十年内激增,给全世界的家庭和医疗保健系统带来沉重负担。这凸显了对阿尔茨海默病治疗干预的迫切需要。越来越多的证据表明,AD 患者血液和中枢神经系统中的炎症非常突出。这些数据表明,全身性炎症在注意力缺失症神经病理学的成因和影响中起着至关重要的作用。根据之前沙利度胺临床试验的经验,我们假设,如果在AD发病过程中的适当时间窗口给药,通过多效性免疫调节剂来那度胺来调节炎症可能会改变AD的病情。因此,在这项二期机制验证研究中,30名有记忆障碍的轻度认知障碍(aMCI)受试者将按1:1的比例接受来那度胺治疗,每天10毫克,为期12个月,然后是6个月的冲洗期。这项研究的首要目标是调查来那度胺对认知能力的影响,并定期进行评估。次要目标是评估来那度胺对aMCI患者的安全性和耐受性,通过不良反应、生命体征、临床生化、体格和神经系统检查进行评估。第三级目标是通过比较用药前后的数据,分析来那度胺对大脑淀粉样蛋白负荷(氟贝他匹PET成像)和神经变性(容积核磁共振成像)的影响。最后,探索性目标将研究血液中的炎症标记物是否可以作为疗效的替代标记物。我们的研究应能确定来那度胺对AD受试者是否安全,以及在痴呆症发病前给药是否能改变AD的临床进展。如果有效,来那度胺将成为第一种能够延缓AD病程的药物,这将为在不久的将来找到更多毒性更小的治疗方法开辟道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Open Access Journal of Clinical Trials
Open Access Journal of Clinical Trials MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
3.90
自引率
0.00%
发文量
2
审稿时长
16 weeks
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