학술논문
Effects of mexiletine on hyperexcitability in sporadic amyotrophic lateral sclerosis: Preliminary findings from a small phase II randomized controlled trial
Document Type
article
Author
Weiss, Michael D; Macklin, Eric A; McIlduff, Courtney E; Vucic, Steve; Wainger, Brian J; Kiernan, Matthew C; Goutman, Stephen A; Goyal, Namita A; Rutkove, Seward B; Ladha, Shafeeq S; Chen, I‐Hweii Amy; Harms, Matthew B; Brannagan, Thomas H; Lacomis, David; Zivkovic, Sasha; Ma, Maxwell; Wang, Leo H; Simmons, Zachary; Rivner, Michael H; Shefner, Jeremy M; Cudkowicz, Merit E; Atassi, Nazem; Group, for the Mexiletine‐2 ALS Study
Source
Muscle & Nerve. 63(3)
Subject
Language
Abstract
BackgroundTo collect preliminary data on the effects of mexiletine on cortical and axonal hyperexcitability in sporadic amyotrophic lateral sclerosis (ALS) in a phase 2 double-blind randomized controlled trial.MethodsTwenty ALS subjects were randomized to placebo and mexiletine 300 or 600 mg daily for 4 wk and assessed by transcranial magnetic stimulation and axonal excitability studies. The primary endpoint was change in resting motor threshold (RMT).ResultsRMT was unchanged with 4 wk of mexiletine (combined active therapies) as compared to placebo, which showed a significant increase (P = .039). Reductions of motor evoked potential (MEP) amplitude (P = .013) and accommodation half-time (P = .002), secondary outcome measures of cortical and axonal excitability, respectively, were also evident at 4 wk on mexiletine.ConclusionsThe relative stabilization of RMT in the treated subjects was unexpected and could be attributed to unaccounted sources of error or chance. However, a possible alternative cause is neuromodulation preventing an increase. The change in MEP amplitude and accommodation half-time supports the reduction of cortical and axonal hyperexcitability with mexiletine.