Clinical Efficacy Trial of Mexiletine for Myotonic Dystrophy Type 1

• The Number of Study Participants Who Safely Tolerated mexiletine [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  Safety and tolerability are monitored by interval laboratory studies, Holter monitoring, resting echocardiograms, dula energy x-ray absorptiometry (DEXA)studies, and physical examinations. The participants have three in-person evaluations at the University of Rochester Clinical Research Center (Months 0, 3, and 6) and telephone evaluations every 2 weeks. Patients complete side effects diaries to record any adverse events in the interval time between the in-person evaluations.
• Myotonia [ Time Frame: 6 months ] [ Designated as safety issue: No ]
• Muscle function and strength [ Time Frame: 6 months ] [ Designated as safety issue: No ]
• Cardiac conduction [ Time Frame: 6 months ] [ Designated as safety issue: No ]
• Quality of Life [ Time Frame: 6 months ] [ Designated as safety issue: No ]

The purpose of this study is to investigate the effects of mexiletine treatment for 6 months on ambulation, myotonia, muscle function and strength, pain, gastrointestinal functioning, cardiac conduction, and quality of life in myotonic dystrophy type 1 (DM1).

This study will provide data on the long term (6 months) safety and efficacy of mexiletine in:

• improving the distance participants are able to walk in six minutes;
• reducing myotonia;
• improving muscle strength;
• increasing lean muscle mass;
• decreasing musculoskeletal pain;
• improving gastrointestinal function and swallowing);
• improving functional abilities;
• decreasing cardiac arrhythmias; and
• improving disease-specific health related quality-of-life.

• Drug: Mexiletine
  150 mg/kg Mexiletine capsules taken by mouth, three times daily for 6 months
  Other Name: Generic name: mexiletine hydrochloride
• Drug: Placebo
  150 mg/kg placebo capsules taken by mouth, three times daily for 6 months

• Active Comparator: Mexiletine
  20 subjects will be randomized (assigned) to receive Mexiletine. Mexiletine is available on the market for the treatment of cardiac arrhythmias, but it is not currently approved for the treatment of myotonia or myotonic dystrophy.
  Intervention: Drug: Mexiletine
• Placebo Comparator: Sugar pill
  20 subjects will be randomized (assigned) to receive placebo (sugar pill). This control group is necessary to definitely establish the antimyotonic efficacy and safety of mexiletine.
  Intervention: Drug: Placebo

• Logigian EL, Martens WB, Moxley RT 4th, McDermott MP, Dilek N, Wiegner AW, Pearson AT, Barbieri CA, Annis CL, Thornton CA, Moxley RT 3rd. Mexiletine is an effective antimyotonia treatment in myotonic dystrophy type 1. Neurology. 2010 May 4;74(18):1441-8.
• Moxley RT 3rd, Logigian EL, Martens WB, Annis CL, Pandya S, Moxley RT 4th, Barbieri CA, Dilek N, Wiegner AW, Thornton CA. Computerized hand grip myometry reliably measures myotonia and muscle strength in myotonic dystrophy (DM1). Muscle Nerve. 2007 Sep;36(3):320-8.

Inclusion Criteria:

• A diagnosis of DM1, confirmed by DM1 genetic mutation
• Ability to walk 30 feet (assistance with cane and/or leg bracing permitted)
• Presence of grip myotonia

Exclusion Criteria:

• Congenital DM1
• Treatment with Mexiletine within past 8 weeks
• Second or third degree heart block, atrial flutter, atrial fibrillation, ventricular arrhythmias, or is receiving medication for treatment of a cardiac arrhythmia
• Receiving another antimyotonia drug
• Liver or kidney disease requiring ongoing treatment
• Has a seizure disorder
• Is pregnant or lactating
• Had severe depression within 3 months or a history of suicide ideation
• Has any one of the following medical conditions: uncontrolled diabetes mellitus, congestive heart failure, symptomatic cardiomyopathy, symptomatic coronary artery disease, cancer (other than skin cancer) less than five years previously, multiple sclerosis, or other serious medical illness.
• Drug or alcohol abuse within 3 months
• Coexistence of another neuromuscular disease
• Is unable to give informed consent
• Severe arthritis or other medical condition (besides DM1) that would significantly impact ambulation