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Abstract
Objective To assess mexiletine's long-term safety and effect on 6-minute walk distance in a well-defined cohort of patients with myotonic dystrophy type 1 (DM1).
Methods We performed a randomized, double-blind, placebo-controlled trial of mexiletine (150 mg 3 times daily) to evaluate its efficacy and safety in a homogenous cohort of adult ambulatory patients with DM1. The primary outcome was change in 6-minute walk distance at 6 months. Secondary outcomes included changes in hand grip myotonia, strength, swallowing, forced vital capacity, lean muscle mass, Myotonic Dystrophy Health Index scores, and 24-hour Holter and ECG results at 3 and 6 months.
Results Forty-two participants were randomized and 40 completed the 6-month follow-up (n = 20 in both groups). No significant effects of mexiletine were observed on 6-minute walk distance, but hand grip myotonia was improved with mexiletine treatment. There were no differences between the mexiletine and placebo groups with respect to the frequency or type of adverse events. Changes in PR, QRS, and QTc intervals were similar in mexiletine- and placebo-treated participants.
Conclusions There was no benefit of mexiletine on 6-minute walk distance at 6 months. Although mexiletine had a sustained positive effect on objectively measured hand grip myotonia, this was not seen in measures reflecting participants' perceptions of their myotonia. No effects of mexiletine on cardiac conduction measures were seen over the 6-month follow-up period.
Classification of Evidence This study provides Class I evidence that for ambulatory patients with DM1, mexiletine does not significantly change 6-minute walk distance at 6 months.
Glossary
- 6MWT=
- 6-minute walk test;
- CI=
- confidence interval;
- DEXA=
- dual-energy X-ray absorptiometry;
- DM1=
- myotonic dystrophy type 1;
- DSMB=
- Data and Safety Monitoring Board;
- GGT=
- γ-glutamyl transferase;
- INQoL=
- Individualized Neuromuscular Quality of Life Questionnaire;
- MDHI=
- Myotonic Dystrophy Health Index;
- PVC=
- premature ventricular contraction
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Class of Evidence: NPub.org/coe
- Received November 6, 2019.
- Accepted in final form August 24, 2020.
- © 2020 American Academy of Neurology
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