A 40-week phase 2B randomized, multicenter, double-blind, placebo-controlled study evaluating the safety and efficacy of memantine in amyotrophic lateral sclerosis.
Publication Title
Muscle & nerve
Document Type
Article
Publication Date
1-1-2025
Keywords
oregon; portland; Humans; Memantine; Amyotrophic Lateral Sclerosis; Male; Female; Double-Blind Method; Middle Aged; Aged; Adult; Aged, 80 and over; Disease Progression; Treatment Outcome; Young Adult; Excitatory Amino Acid Antagonists
Abstract
INTRODUCTION: 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.
AIMS: 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.
METHODS: 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.
RESULTS: 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.
DISCUSSION: In this study, memantine did not impact ALS disease progression or neuropsychiatric symptoms. Trials with remote enrollment may help trial participation and success.
Area of Special Interest
Neurosciences (Brain & Spine)
Specialty/Research Institute
Neurosciences
DOI
10.1002/mus.28287
