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Study Description

Non-dystrophic myotonias are a group of rare muscle disorders caused by abnormalities in different muscle cell membrane proteins. Patients experience delayed muscle relaxation that causes impaired physical activity, stiffness, and pain. Mexiletine has been shown to be beneficial for symptoms of myotonia in case reports of patients with non-dystrophic myotonia, however, current management of these patients primarily depends on individual practitioners' preference. This study is a placebo-controlled, double-blind, cross-over treatment trial using mexiletine in non-dystrophic myotonias. The results, if positive, will permit the identification of mexiletine as an effective therapy for myotonia, making it a first-line therapy for patients with non-dystrophic myotonia.

The specific aim of this proposal is to perform a randomized, double-blind, placebo-controlled cross-over study to assess whether mexiletine improves both quantitative and qualitative measures of myotonia in patients with non-dystrophic myotonia. Given the rarity of non-dystrophic myotonia, large randomized controlled treatment trials in these disorders have not been feasible in the past.

Primary Outcome Measure: Patient-assessed symptom: stiffness as measured by an Interactive Voice Response Diary (IVR).

Secondary Outcome Measures: a) patient-assessed pain, weakness, and fatigue as measured by IVR; b) clinical myotonia assessment; c) quality of life as measured by INQoL, SF36; d) a quantitative measure of grip myotonia; e) measurement of CMAP after short and long exercise; f) grading of myotonia on needle EMG.

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  • Study Design:
    • Case Set
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    • Case Set
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Publicly Available Data (Public ftp)

Connect to the public download site. The site contains release notes and manifests. The site also contains data dictionaries, variable summaries, documents, and truncated analyses, whenever available.

Study Inclusion/Exclusion Criteria

a) Inclusion Criteria (Participants must meet all of these):

  1. At least 16 years of age
  2. Clinical symptoms or signs suggestive of myotonic disorders
  3. Presence of myotonic potentials on electromyography (EMG)
  4. Participation in the Non-Dystrophic Myotonia Natural History study; or a new patient with genetically confirmed NDM; or a new patient with a first degree relative (parent, sibling, or child) with genetically confirmed NDM; or a new patient with clinical features of NDM in whom the mutation has not been localized, is DM1 and DM2 negative.
  5. If patients are on either of the following medications, they must be on a stable dose for 30 days prior to enrollment. Medications are:
  6. a. fibrate acid derivatives
    b. hydroxymethylglutaryl CoA reductase inhibitors.

b) Exclusion Criteria:

  1. Inability or unwillingness to provide informed consent.
  2. Other neurological conditions that might affect the assessment of the study measurements.
  3. Genetic confirmed DM1 (CTG > 50 repeats), or DM2.
  4. Patients with existing cardiac conduction defects, evidenced on EKG including but not limited to the following conditions: malignant arrhythmia or cardiac conduction disturbances (such as second degree AV block, third degree AV block, or prolonged QT interval >500 ms or QRS duration > 150 msec).
  5. Current use of the following antiarrhythmic medication for a cardiac disorder: flecainide acetate, encainide, disopyramide, procainamide, quinidine, propafenone or mexiletine.
  6. Women who are pregnant or lactating.
  7. Patients currently on medications for myotonia such as phenytoin and flecainide acetate within 5 days of enrollment, carbamazepine and mexiletine within 3 days of enrollment, or acetazolamide, propafenone, procainamide, disopyramide, quinidine and encainide within 2 days of enrollment.
  8. Patients with an existing permanent pacemaker.
  9. Patients with renal or hepatic disease, heart failure, or seizure disorders.
  10. Patients on medications that produce myotonia. This includes one or more of the following:
  11. a. chloroquine
    b. colchicines

Study History

  • Study Activated December 19, 2008
  • First Accrual December 23, 2008
  • Study Final Closed May 1, 2012

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