Effects of mexiletine on hyperexcitability in sporadic amyotrophic lateral sclerosis: Preliminary findings from a small phase II randomized controlled trial. Issue 3 (31st December 2020)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Muscle & nerve. Volume 63:Issue 3(2021)
• Page Start: 371
• Page End: 383
• Publication Date: 2020-12-31
• Subjects: amyotrophic lateral sclerosis -- axonal excitability -- outcome research -- randomized controlled clinical trial -- transcranial magnetic stimulation; Neuromuscular diseases -- Periodicals; Muscles -- Periodicals; Nerves -- Periodicals; 616.74
• DOI: 10.1002/mus.27146
• Languages: English
• ISSNs: 0148-639X

Abstract

Abstract: Background: To 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. Methods: Twenty 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). Results: RMT 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. Conclusions: The 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.