Mexiletine and Non Dystrophic Myotonias
Condition: Non-dystrophic Myotonias; Paramyotonia Congenita; Myotonia Congenita
MeSH terms: Myotonia Congenita; Myotonic Disorders; Myotonia
Study type: Interventional
Phase: Phase 3

Summary: 
      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
    

Detailed description: 
      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
    

Intervention name(s): Mexiletine; placebo
Intervention type(s): Drug; Drug
Intervention description(s): Blisters of 10 capsules of 200 mg mexiletine hydrochloride.
Patients will receive gradual dose of the treatment as it would be done in clinical practice.
Mexiletine will be started at 200 mg / day (1 capsule to be taken at the beginning of the meal) and will be increased by 200mg every 3 days to reach a maximum of 600mg / day in 3 taken in 1 week.
The duration of each treatment period is 18 days minimum (maximum 22 days).
Intervention MeSH terms: Mexiletine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: non-dystrophic myotonias; paramyotonia congenita; myotonia congenita; Mexiletine; Randomized clinical trial