Bhai Salman, Levine Todd, Moore Dan, Bowser Robert, Heim Andrew J, Walsh Maureen, Shibani Aziz, Simmons Zachary, Grogan James, Goyal Namita A, Govindarajan Raghav, Hussain Yessar, Papsdorf Tania, Schwasinger-Schmidt Tiffany, Olney Nick, Goslin Kim, Pulley Michael, Kasarskis Edward, Weiss Michael, Katz Susan W, Moser Suzan, Jabari Duaa, Jawdat Omar, Statland Jeffrey, Dimachkie Mazen M, Barohn Richard
University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Neuromuscular Center, Institute for Exercise and Environmental Medicine, Texas Health Dallas, Dallas, Texas, USA.
Muscle Nerve. 2025 Jan;71(1):63-72. doi: 10.1002/mus.28287. Epub 2024 Nov 7.
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease with no known cure, limited treatment options with minimal benefits, and significant unmet need for disease modifying therapies.
This study investigated memantine's impact on ALS progression, with an additional focus on the effects of memantine on cognitive and behavioral changes associated with the disease.
A randomized, double-blind, placebo-controlled clinical trial was conducted from December 2018 to September 2020. ALS patients were enrolled in-person and remotely across 13 sites in the United States. Participants were randomized to memantine (20 mg twice daily) or placebo in a 2:1 ratio and completed 36 weeks of treatment. The primary outcome of disease progression was assessed by the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), and blood was collected for biomarker analysis.
Of the 99 participants enrolled in the study, 89 were randomized to memantine or placebo (ages 24-83 years, male-to-female ratio ~3:2). Fifty-two participants completed the study treatment with no significant differences in disease progression, biomarker changes (including neurofilament light chain [NfL]), or neuropsychiatric testing noted between the groups. Initial NfL values correlated with the rate of ALSFRS-R decline.
In this study, memantine did not impact ALS disease progression or neuropsychiatric symptoms. Trials with remote enrollment may help trial participation and success.
肌萎缩侧索硬化症（ALS）是一种快速进展的神经退行性疾病，目前尚无已知的治愈方法，治疗选择有限且益处极小，对疾病修饰疗法存在重大未满足需求。
本研究调查了美金刚对ALS进展的影响，并额外关注美金刚对与该疾病相关的认知和行为变化的影响。
于2018年12月至2020年9月进行了一项随机、双盲、安慰剂对照的临床试验。ALS患者在美国13个地点亲自或通过远程方式入组。参与者以2:1的比例随机分配至美金刚组（每日两次，每次20毫克）或安慰剂组，并完成36周的治疗。通过修订的肌萎缩侧索硬化症功能评定量表（ALSFRS-R）评估疾病进展的主要结局，并采集血液进行生物标志物分析。
在该研究纳入的99名参与者中，89名被随机分配至美金刚组或安慰剂组（年龄24 - 83岁，男女比例约为3:2）。52名参与者完成了研究治疗，两组之间在疾病进展、生物标志物变化（包括神经丝轻链[NfL]）或神经精神测试方面未发现显著差异。初始NfL值与ALSFRS-R下降率相关。
在本研究中，美金刚并未影响ALS疾病进展或神经精神症状。采用远程入组的试验可能有助于提高试验参与度和成功率。
