Mexiletine for Muscle Cramps in Charcot Marie Tooth Disease
Condition: Charcot Marie Tooth Disease
MeSH terms: Muscle Cramp; Tooth Diseases; Charcot-Marie-Tooth Disease; Nerve Compression Syndromes; Hereditary Sensory and Motor Neuropathy
Intervention: Placebo; Mexiletine
Intervention description: 240 mg lactose powder in a size 3 capsule taken by mouth 3 times daily for 5-7 days; 150 mg Mexiletine taken by mouth in capsule form 3 times daily for 5-7 days
Intervention MeSH terms: Mexiletine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Charcot Marie Tooth Disease is a family of inherited peripheral neuropathies, with over 70
      causative genes identified to date.1-4 Muscle cramps are frequent in CMT, affecting up to 85%
      of patients with some subtypes of CMT. These cramps impact quality of life and have been
      identified as an important therapeutic target for clinical trials in CMT.1-4 There is no FDA
      approved treatment for muscle cramps.5 Mexiletine is a sodium channel blocker approved for
      treatment of arrhythmias. As a sodium channel blocker, mexiletine offers the promise of
      effective therapy for muscle cramps.
    

Eligibility criteria:

        Inclusion Criteria:

          -  The subject has known CMT, previously diagnosed by a neurologist with subspeciality
             expertise in neuromuscular disorders/peripheral neuropathy. The diagnosis of CMT
             relies on a combination of clinical history (including family history), neurological
             examination electrophysiological features, and prior genetic testing results.

               -  The subject is at least 18 years old, and has signed the Informed Consent Form.

               -  The subject is ambulatory (cane, walker, orthoses allowed).

               -  The subject has experienced muscle cramps and has known provokable hamstring or
                  calf muscle cramps on MVC.

               -  The subject has a reliable method of birth control (if a female subject of child
                  bearing potential). Reliable birth control is defined as Hormonal contraception
                  Intrauterine contraception/device Any two barrier methods (combination of male or
                  female condom with diaphragm sponge or cervical cap) together with spermicidal
                  foam/gel/film/cream/suppository True abstinence

        Exclusion Criteria:

          -  The subject has a known neuropathy from another source (e.g., diabetes, drug induced,
             alcohol, etc.).

               -  The subject has an untreated medical disorder known to predispose to muscle
                  cramps

               -  The subject is pregnant or nursing, has a known mexiletine allergy or has taken
                  mexiletine in the past 12 weeks.

               -  The subject is participating in another therapeutic trial.

               -  The subject has second or 3rd degree heart block, atrial flutter/fibrillation,
                  ventricular arrhythmias, or is receiving treatment of a cardiac arrhythmia.

               -  The subject is currently taking another agent for muscle cramps or a muscle
                  relaxant (e.g., benzodiazepine, baclofen, tizanidine, soma, meprobromate).

               -  The subject is on another sodium channel blocker or medication that precludes
                  administration of mexiletine.

               -  The subject has known diabetes mellitus, liver or kidney disease requiring
                  ongoing treatment, untreated thyroid dysfunction, symptomatic cardiomyopathy, or
                  symptomatic coronary artery disease.

               -  The subject, in the opinion of the investigator, is unsuitable for enrollment for
                  any other reason