A randomized, placebo-controlled trial of memantine for functional disability in amyotrophic lateral sclerosis

Abstract

Our objective is to describe the results of a phase II/III, 12-months, double-blinded, single-centre, randomized, parallel (1:1), clinical trial performed to evaluate the efficacy and safety of memantine in ALS. Patients with probable or definite ALS of less than 36 months disease duration and progression over a one-month lead-in period were randomly assigned to placebo or memantine at 20 mg/day. The primary endpoint was 12-months ALSFRS decline. Forced vital capacity, manual muscle testing, visual analogue scale, quality of life, motor unit number estimation and neurophysiological index were the secondary endpoints. The number of patients included was based on the assumption of a 50% change in the ALSFRS decline. Safety and adverse events were evaluated. Sixty-three patients were included in the trial. Memantine did not show more adverse events or laboratory changes than placebo. Primary and secondary outcomes were not different between groups by intention-to-treat and per-protocol analysis. The most sensitive measurements were neurophysiological, which declined linearly over time. In conclusion, the results of this study show that memantine is well tolerated and safe in ALS patients. We did not observe any evidence of efficacy for memantine but we cannot exclude a positive outcome on survival.

Key words::

• Amyotrophic lateral sclerosis
• clinical trial
• memantine
• neurophysiological index
• progression

Acknowledgments

This trial was partially funded by an unrestricted research grant from Lundbeck Portugal, Lda, which provided the active drug and matched placebo. Lundbeck Portugal, Lda did not participate in any stage of the trial including the design of the protocol or data analysis.

We are grateful to Joaquim Ferreira for helpful suggestions in trial design, to Manuela Alves for trial monitoring, to Ana Noronha for randomization and to Margarida Fernandes for administrative work.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.