Effectiveness of Mexiletine for Treating People With Non-Dystrophic Myotonia

Richard Barohn, MD

Status and phase: Completed; Phase 2

Conditions: Myotonia; Non-Dystrophic Myotonia

Treatments: Drug: Mexiletine; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT00832000

11050 (Registry Identifier)

FDA OPD RO1FD003454

Details and patient eligibility

About

Nondystrophic myotonias (NDM) are neuromuscular disorders caused by genetic abnormalities in certain muscle cell membrane proteins. The proteins affect muscle contraction. Individuals with NDM experience limited muscle relaxation, which then can cause pain, weakness, incoordination, and impaired physical activity and function. Because NDM is very rare, information on the best way to treat people with the disorders is lacking, and there are no FDA-approved therapies. The purpose of this study is to determine the effectiveness of the medication mexiletine in treating people with NDM.

Full description

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.

Funded by FDAOPD RO1 0003454.

Enrollment: 59 patients

Sex: All

Ages: 16+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Clinical symptoms or signs suggestive of myotonic disorders
• Presence of myotonic potentials on electromyography (EMG)
• Participant in the Non-Dystrophic Natural History study (RDCRN 5303) or a new patient with confirmed non-dystrophic myotonia

Exclusion criteria

• Other neurological condition that might affect the assessment of the study measurements
• Genetic confirmation of DM1 (more than 50 repeats of CTG) or DM2
• Existing cardiac conduction defects, as evidenced on EKG, including but not limited to the following conditions: malignant arrhythmia or cardiac conduction disturbances (e.g., second degree AV block, third degree AV block, or prolonged QT interval)
• Existing permanent pacemaker
• Current use of any of the following antiarrhythmic medications for a cardiac disorder: flecainide acetate, encainide, disopyramide, procainamide, quinidine, propafenone, or mexiletine
• Use of medications for myotonia, such as phenytoin and flecainide acetate, within 5 days of study entry; carbamazepine and mexiletine within 3 days of study entry; or propafenone, procainamide, disopyramide, quinidine, and encainide within 2 days of study entry
• Use of medications that produce myotonia, which may include fibrate acid derivatives, hydroxymethylglutaryl CoA reductase inhibitors, chloroquine, and colchicines
• Kidney or liver disease
• Heart failure
• Seizure disorder
• Pregnant or breastfeeding

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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59 participants in 2 patient groups

1

Experimental group

Description:

Participants will receive mexiletine for 4 weeks, then no intervention for 1 week, and finally placebo for 4 weeks.

Treatment:

Drug: Placebo

Drug: Mexiletine

2

Experimental group

Description:

Participants will receive placebo for 4 weeks, then no intervention for 1 week, and finally mexiletine for 4 weeks.

Treatment:

Drug: Placebo

Drug: Mexiletine