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

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.

• Authors: Chad Heatwole, Elizabeth Luebbe, Spencer Rosero, Katy Eichinger, William Martens, James Hilbert, Jeanne Dekdebrun, Nuran Dilek, Christine Zizzi, Nicholas Johnson, Araya Puwanant, Rabi Tawil, Giovanni Schifitto, Christopher A Beck, J Franklin Richeson, Wojciech Zareba, Charles Thornton, Michael P McDermott, Richard Moxley 3rd
• Journal: Neurology (Neurology) Vol. 96 Issue 2 Pg. e228-e240 (01 12 2021) ISSN: 1526-632X [Electronic] United States
• PMID: 33046619 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, U.S. Gov't, P.H.S.)
• Copyright: © 2020 American Academy of Neurology.

Chemical References

• Voltage-Gated Sodium Channel Blockers
• Mexiletine

Topics

• Adult
• Cohort Studies
• Double-Blind Method
• Electrocardiography (drug effects, trends)
• Female
• Hand Strength (physiology)
• Humans
• Male
• Mexiletine (pharmacology, therapeutic use)
• Middle Aged
• Myotonic Dystrophy (diagnosis, drug therapy, physiopathology)
• Voltage-Gated Sodium Channel Blockers (pharmacology, therapeutic use)
• Walk Test (methods, trends)