Mexiletine for Muscle Cramps in Charcot Marie Tooth Disease

NCT02561702 | Completed Phase 2 Results

• 1 other identifier: RSRB00057653
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Charcot Marie Tooth Disease

Outcome Measures

Primary Outcomes (2)

• Number of Participants With a Decrease in Cramp Duration

  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.

  120 minutes

• Number of Participants With a Decrease in Cramp Intensity

  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.

  120 minutes

Study Arms (2)

Mexiletine first/placebo second

EXPERIMENTAL

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

Other: Placebo; Drug: Mexiletine

placebo first/mexiletine second

EXPERIMENTAL

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

Other: Placebo; Drug: Mexiletine

Interventions

Placebo OTHER

240 mg lactose powder in a size 3 capsule taken by mouth 3 times daily for 5-7 days

Also known as: lactose powder

Mexiletine first/placebo second; placebo first/mexiletine second

Mexiletine DRUG

150 mg Mexiletine taken by mouth in capsule form 3 times daily for 5-7 days

Mexiletine first/placebo second; placebo first/mexiletine second

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Rochester: lead

Study Sites (1)

University of Rochester

Rochester, New York, 14642, United States

Location

MeSH Terms

Conditions

Charcot-Marie-Tooth Disease

Interventions

Mexiletine

Condition Hierarchy (Ancestors)

Hereditary Sensory and Motor Neuropathy; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Phenyl Ethers; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: David Herrmann
• Organization: University of Rochester

david_herrmann@urmc.rochester.edu

585-275-4568

Study Officials

• David Herrmann, MD

  University of Rochester

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 24, 2015
• First Posted: September 28, 2015
• Study Start: September 1, 2015
• Primary Completion: December 31, 2016
• Study Completion: December 31, 2016
• Last Updated: March 26, 2018
• Results First Posted: March 26, 2018

Record last verified: 2018-02

Locations

US (1)