Effectiveness of Mexiletine for Treating People With Non-Dystrophic Myotonia

NDM are neuromuscular disorders that are caused by mutations in skeletal muscle ion
channels, usually voltage-dependent sodium and chloride channels. The poorly functioning
channels result in impaired muscle relaxation after contraction, which is also called
myotonia. Mexiletine is an antiarrhythmic medication that has a high affinity for muscle
sodium channels and may have the ability to correct delayed inactivation of sodium channels.
In case reports and single-blind clinical trials, mexiletine was shown to reduce symptoms of
myotonia. Currently, there is no standard strategy for treating people with NDM, and
effective treatment options are needed. This study will determine the effectiveness of
mexiletine in treating people with NDM.

Participation in this study will last 9 weeks and will involve two separate 4-week treatment
periods, with a 1-week washout period between them. During the first treatment period,
participants will be randomly assigned to receive either mexiletine or placebo, both of
which will be taken three times a day. This will be followed by 1 week of no treatment.
During the second treatment period, participants will receive whichever treatment they did
not receive initially and will follow the same dosing schedule.

Participants will attend five study visits that will occur at screening and Weeks 0, 4, 5,
and 9. Screening will include blood and urine sampling, electrocardiography (EKG), and a
medical history. The remaining visits will include a physical examination, a grip test,
exercise tests, nerve conduction tests, blood sampling, questionnaires, and electromyography
(EMG). EKG will be repeated at Weeks 4, 5, and 9. Throughout the study, participants will
phone in daily to report their symptoms. There will be no follow-up visits.