{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T22:54:53Z","timestamp":1788908093295,"version":"build-2803163510"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T00:00:00Z","timestamp":1730937600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000038","name":"U.S. Food and Drug Administration","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A randomized, double\u2010blind, placebo\u2010controlled clinical trial was conducted from December 2018 to September 2020. ALS patients were enrolled in\u2010person and remotely across 13 sites in the United States. Participants were randomized to memantine (20\u2009mg twice daily) or placebo in a 2:1 ratio and completed 36\u2009weeks of treatment. The primary outcome of disease progression was assessed by the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS\u2010R), and blood was collected for biomarker analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the 99 participants enrolled in the study, 89 were randomized to memantine or placebo (ages 24\u201383\u2009years, male\u2010to\u2010female ratio ~3:2). Fifty\u2010two 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\u2010R decline.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>In this study, memantine did not impact ALS disease progression or neuropsychiatric symptoms. Trials with remote enrollment may help trial participation and success.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.28287","type":"journal-article","created":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T07:33:42Z","timestamp":1731051222000},"page":"63-72","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A 40\u2010week phase <scp>2B<\/scp> randomized, multicenter, double\u2010blind, placebo\u2010controlled study evaluating the safety and efficacy of memantine in amyotrophic lateral sclerosis"],"prefix":"10.1002","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4702-9380","authenticated-orcid":false,"given":"Salman","family":"Bhai","sequence":"first","affiliation":[{"name":"University of Texas Southwestern Medical Center  Dallas Texas USA"},{"name":"Neuromuscular Center, Institute for Exercise and Environmental Medicine Texas Health Dallas  Dallas Texas 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Olney","sequence":"additional","affiliation":[{"name":"Providence Brain and Spine Institute  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Goslin","sequence":"additional","affiliation":[{"name":"Providence Brain and Spine Institute  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Pulley","sequence":"additional","affiliation":[{"name":"University of Florida College of Medicine Jacksonville  Jacksonville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Kasarskis","sequence":"additional","affiliation":[{"name":"University of Kentucky  Lexington Kentucky 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