Mexiletine and Non Dystrophic Myotonias

Overview

Treatment strategies in non-dystrophic myotonias are based on selective case reports, clinical experience and theoretical benefit. Presently, the most promising antimyotonic medication is mexiletine (MEX) but its manufacturing was stopped. The proposed randomized, double-blind, placebo-controlled, crossover trial is designed to: 1. study the safety and efficacy of mexiletine for the treatment of non-dystrophic myotonias 2. validate electromyographic tests as a standardized outcome measure of myotonia 3. assess the reliability and validity of a new clinical rating scale for myotonia

A. Specific aims Treatment strategies in non-dystrophic myotonias are based on selective case reports, clinical experience and theoretical benefit. Presently, the most promising antimyotonic medication is mexiletine (MEX) but its manufacturing was stopped. The proposed randomized, double-blind, placebo-controlled, crossover with wash-out trial is designed to: * study the safety and efficacy of mexiletine for the treatment of non-dystrophic myotonias * validate electromyographic tests as a standardized outcome measure of myotonia * assess the reliability and validity of a new clinical rating scale for myotonia B. Research design Because of their differing phenotypes, 12 Paramyotonia Congenita and 12 Myotonia Congenita subjects will be enrolled in a stratified trial C. Outcome variables 1. primary outcome variable: the score of stiffness severity on a self-assessment scale (100 mm VAS) measured at baseline, at the end of phase I and phase II. 2. secondary outcome measures: * of efficacy: * standardized EMG measures after repetitive short exercise test at cold and long exercise test * chair test: time needed to stand up from a chair, walk around it and sit down again * severity and disability scale of myotonia to be validated) * quality of life scale (INQOL) * rate of drop-outs * of safety: * adverse event frequency and severity * EKG D. Perspectives It is anticipated that the trial will: 1. provide data that justify recommendations for treatment strategies for myotonic patients 2. provide data to justify AFSAPPS regulatory approval of mexiletine for treatment of myotonia in order to guarantee the availability of the drug for patients 3. develop standardized diagnostic and treatment assessment for non-dystrophic myotonias