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Effects of mexiletine on hyperexcitability in sporadic amyotrophic lateral sclerosis: Preliminary findings from a small phase II randomized controlled trial
Author(s) -
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 IHweii 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
Publication year - 2021
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.27146
Subject(s) - mexiletine , amyotrophic lateral sclerosis , transcranial magnetic stimulation , medicine , anesthesia , placebo , randomized controlled trial , stimulation , neuroscience , psychology , pathology , alternative medicine , disease
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.