A single blind randomized controlled clinical trial of mexiletine in amyotrophic lateral sclerosis: Efficacy and safety of sodium channel blocker phase II trial

Amyotroph Lateral Scler Frontotemporal Degener. 2015;16(5-6):353-8. doi: 10.3109/21678421.2015.1038277. Epub 2015 May 11.


Fasciculations are characteristic features of amyotrophic lateral sclerosis (ALS), and suggest motor nerve hyperexcitability. Recent reports have shown that an increase in persistent nodal sodium current is associated with shorter survival in ALS patients. This objective of this trial is to study the efficacy and safety of mexiletine, a sodium channel blocker, for ALS. Sixty eligible participants were randomly allocated (1:1) to riluzole 100 mg or riluzole plus mexiletine 300 mg. The primary endpoint was change in the revised ALS functional rating scale (ALSFRS-R) scores during six months. We also monitored strength-duration time constant (SDTC, a measure of persistent sodium current) in median motor axons. Results showed that during six months of treatment, changes in the ALSFRS-R score and SDTC were -7.0 ± 7.1 and -0.04 ± 0.1, respectively, in the riluzole group and -6.9 ± 6.4 and 0.04 ± 0.1, respectively, in the mexiletine group (p = 0.96 and 0.049). Adverse events amounted 20% in the riluzole and 33% in the mexiletine groups. In conclusion, the results suggest that daily 300 mg mexiletine has no effects on axonal sodium current and ALSFRS-R deterioration in ALS. We have to attempt another trial using a higher dose of mexiletine or other agents to suppress sodium currents and ALS progression in the future.

Keywords: Mexiletine; amyotrophic lateral sclerosis; clinical trial; nerve excitability; sodium current.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amyotrophic Lateral Sclerosis / drug therapy*
  • Amyotrophic Lateral Sclerosis / physiopathology
  • Animals
  • Dose-Response Relationship, Drug
  • Evoked Potentials, Motor / drug effects
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Mexiletine / therapeutic use*
  • Middle Aged
  • Neural Conduction / drug effects
  • Neural Conduction / physiology
  • Severity of Illness Index
  • Single-Blind Method
  • Treatment Outcome*
  • Voltage-Gated Sodium Channel Blockers / therapeutic use*


  • Voltage-Gated Sodium Channel Blockers
  • Mexiletine