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Effects of mexiletine on hyperexcitability in sporadic amyotrophic lateral sclerosis: Preliminary findings from a small phase II randomized controlled trial
- 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
- et al.
Published Web Location
https://doi.org/10.1002/mus.27146Abstract
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.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.
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