Mexiletine in Myotonic Dystrophy Type 1: A Randomized, Double-Blind, Placebo-Controlled Trial

Area of Science:

• Neurology
• Clinical Trials
• Pharmacology

Background:

• Myotonic dystrophy type 1 (DM1) is a progressive genetic disorder.
• Limited therapeutic options exist for DM1, impacting quality of life.
• Mexiletine is an antiarrhythmic drug with potential muscle relaxant properties.

Purpose of the Study:

• To evaluate the long-term safety and efficacy of mexiletine in adult ambulatory patients with DM1.
• To assess mexiletine's effect on the 6-minute walk distance (6MWD) as a primary outcome.
• To investigate secondary outcomes including myotonia, strength, and cardiac function.

Main Methods:

• A randomized, double-blind, placebo-controlled trial was conducted.
• Participants received mexiletine (150 mg 3 times daily) or placebo for 6 months.
• Primary endpoint was change in 6MWD; secondary endpoints included myotonia, strength, and ECG parameters.

Main Results:

• No significant improvement in 6MWD was observed in the mexiletine group compared to placebo.
• Mexiletine significantly improved objective hand grip myotonia measurements.
• Adverse events and cardiac conduction changes (PR, QRS, QTc) were similar between groups.

Conclusions:

• Mexiletine does not improve 6-minute walk distance in DM1 patients.
• Sustained improvement in objective hand grip myotonia was noted, but not in subjective measures.
• Mexiletine demonstrated a favorable safety profile with no impact on cardiac conduction over 6 months.