Mexiletine for Muscle Cramps in Charcot Marie Tooth Disease

Phase 2

Completed

• Conditions: Charcot Marie Tooth Disease
• Interventions: Other: Placebo; Drug: Mexiletine

• Registration Number: NCT02561702
• Lead Sponsor: University of Rochester

Brief 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.

Detailed Description

This study will provide data on the short term efficacy of oral mexiletine in helping to prevent muscle cramps in adults with CMT. The study will also assess the short-term safety and tolerability of low dose mexiletine in adults with CMT.

Study Timeline

• Study Start: 2015-09
• Study First Submitted: 2015-09-24
• Study First Submitted QC: 2015-09-25
• Study First Posted: 2015-09-28
• Primary Completion: 2016-12-31
• Study Completion: 2016-12-31
• Results First Submitted: 2018-01-25
• Status Verified: 2018-02
• Results First Submitted QC: 2018-02-23
• Last Update Submitted: 2018-02-23
• Results First Posted: 2018-03-26
• Last Update Posted: 2018-03-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 4

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Mexiletine first/placebo second	Placebo	Participants will receive 150 mg of mexiletine by mouth 3 times daily for 5-7 days followed by 7 day washout period and 5-7 days of placebo (240 mg of lactose powder) taken by mouth 3 times daily
placebo first/mexiletine second	Placebo	Participants will receive placebo (240 mg of lactose powder) taken by mouth 3 times daily for 5-7 days followed by 7 day washout period and 5-7 days of 150 mg of mexiletine by mouth 3 times daily
Mexiletine first/placebo second	Mexiletine	Participants will receive 150 mg of mexiletine by mouth 3 times daily for 5-7 days followed by 7 day washout period and 5-7 days of placebo (240 mg of lactose powder) taken by mouth 3 times daily
placebo first/mexiletine second	Mexiletine	Participants will receive placebo (240 mg of lactose powder) taken by mouth 3 times daily for 5-7 days followed by 7 day washout period and 5-7 days of 150 mg of mexiletine by mouth 3 times daily

Primary Outcome Measures

Name	Time	Method
Number of Participants With a Decrease in Cramp Duration	120 minutes	Participant will be evaluated for muscle cramps 120 minutes following a single dose of oral mexiletine. The Clinical Evaluator applied pressure to provoke hamstring cramps bilaterally, one at a time 2 hours after dose. The cramp duration in seconds of the right hamstring was used.
Number of Participants With a Decrease in Cramp Intensity	120 minutes	Participant will be evaluated for muscle cramps 120 minutes following a single dose of oral mexiletine. The Clinical Evaluator applied pressure to provoke hamstring cramps bilaterally, one at a time 2 hours after dose. The cramp intensity of the right hamstring was reported by the subject on a scale of 1-10 with 1 being weak and 10 being severe.

Trial Locations

Locations (1)

University of Rochester; 🇺🇸 Rochester, New York, United States