Mexiletine in myotonic dystrophy type-1: A randomized, double-blind, placebo-controlled trial.

Objective To assess mexiletine9s long-term safety and effect on 6 minute walk distance in a well-defined cohort of myotonic dystrophy type-1 (DM1) patients. 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 DM1 patients. 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 EKG 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 six-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 participants9 perceptions of their myotonia. No effects of mexiletine on cardiac conduction parameters 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 six-minute walk distance at 6 months.