Clinical Efficacy Trial of Mexiletine for Myotonic Dystrophy Type 1

May 21, 2018 updated by: Chad Heatwole, University of Rochester

A Randomized, Placebo Controlled, Clinical Efficacy Trial of Mexiletine for Myotonic Dystrophy Type-1 (DM1)

The purpose of this study is to investigate the effects of mexiletine treatment for 6 months on ambulation, myotonia, muscle function and strength, pain, gastrointestinal functioning, cardiac conduction, and quality of life in myotonic dystrophy type 1 (DM1).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study will provide data on the long term (6 months) safety and efficacy of mexiletine in:

  • improving the distance participants are able to walk in six minutes;
  • reducing myotonia;
  • improving muscle strength;
  • increasing lean muscle mass;
  • decreasing musculoskeletal pain;
  • improving gastrointestinal function and swallowing);
  • improving functional abilities;
  • decreasing cardiac arrhythmias; and
  • improving disease-specific health related quality-of-life.

Study Type

Interventional

Enrollment (Actual)

42

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Rochester, New York, United States, 14642
        • University of Rochester Medical Center, Department of Neurology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • A diagnosis of DM1, confirmed by DM1 genetic mutation
  • Ability to walk 30 feet (assistance with cane and/or leg bracing permitted)
  • Presence of grip myotonia

Exclusion Criteria:

  • Congenital DM1
  • Treatment with Mexiletine within past 8 weeks
  • Second or third degree heart block, atrial flutter, atrial fibrillation, ventricular arrhythmias, or is receiving medication for treatment of a cardiac arrhythmia
  • Receiving another antimyotonia drug
  • Liver or kidney disease requiring ongoing treatment
  • Has a seizure disorder
  • Is pregnant or lactating
  • Had severe depression within 3 months or a history of suicide ideation
  • Has any one of the following medical conditions: uncontrolled diabetes mellitus, congestive heart failure, symptomatic cardiomyopathy, symptomatic coronary artery disease, cancer (other than skin cancer) less than five years previously, multiple sclerosis, or other serious medical illness.
  • Drug or alcohol abuse within 3 months
  • Coexistence of another neuromuscular disease
  • Is unable to give informed consent
  • Severe arthritis or other medical condition (besides DM1) that would significantly impact ambulation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Mexiletine
20 subjects will be randomized (assigned) to receive Mexiletine. Mexiletine is available on the market for the treatment of cardiac arrhythmias, but it is not currently approved for the treatment of myotonia or myotonic dystrophy.
Drug: Mexiletine
150 mg/kg Mexiletine capsules taken by mouth, three times daily for 6 months
Other Names:
  • Generic name: mexiletine hydrochloride
Placebo Comparator: Sugar pill
20 subjects will be randomized (assigned) to receive placebo (sugar pill). This control group is necessary to definitely establish the antimyotonic efficacy and safety of mexiletine.
Drug: Placebo
150 mg/kg placebo capsules taken by mouth, three times daily for 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Change From Baseline in Ambulation Using the 6 Minute Walk Distance
Time Frame: Baseline to 6 months
During this assessment, participants were asked to walk as far as they could back and forth on a fixed 20 meter route for 6 minutes. The total distance walked during the 6 minutes was recorded in meters. Change from baseline was defined as the difference between the average 6 minute walk distance at baseline and the average 6 minute walk distance at 6 months.
Baseline to 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants That Had a Dose Reduction or a Study Drug Withdrawal or Suspension Over 6 Months
Time Frame: 6 months
Adverse events were monitored at the three in-person evaluations (Months 0, 3, and 6), at telephone evaluations every 2 weeks, and via patient-completed side effect diaries. The study investigators and safety monitoring committee reviewed adverse events and made decisions regarding drug withdrawals, suspensions, and dose reductions as needed.
6 months
Mean Change From Baseline in Quantitative Measure of Hand Grip Myotonia
Time Frame: Baseline to 6 months
Relaxation time of the long finger flexor muscles of the right hand after a maximum voluntary isometric contraction performed in a standardized fixed position of the right arm elbow/wrist/hand. Relaxation time for this measurement is defined as the time to relax from 90% to 5% of the maximum isometric force of contraction of the hand (the first of 6 serial contractions averaged over two consecutive trials performed 10 minutes apart).
Baseline to 6 months
Mean Change From Baseline in Manual Muscle Testing (MMT) Score
Time Frame: Baseline to 6 months
Manual muscle testing was performed on 26 muscle groups (shoulder abductors, elbow flexors, wrist flexors, wrist extensors, hip flexors, knee extensors, hip extensors, knee flexors, hip abductors, elbow extensors, ankle dorsiflexors, and plantar flexors on the right and left plus neck extensor and neck flexors). The muscles were tested in various positions including sitting, supine, prone, and side lying and each graded on a modification of the Medical Research Council (MRC) scale of 0 to 5 (5 representing normal strength). Average MMT score is derived by averaging the individual MMT scores across the 26 individual muscles.
Baseline to 6 months
Mean Change From Baseline in PR, QRS, and QTc Intervals, and Average Minimum Heart Rate (HR) Via Electrocardiogram (ECG) Monitoring
Time Frame: Baseline to 6 Months
PR, QRS, and QTc intervals as well as average minimum heart rate (HR) were obtained through standard 12 lead electrocardiograms (ECGs). Values were computer generated and verified by the study investigator and study cardiologist.
Baseline to 6 Months
Mean Change From Baseline in Patient-Reported Disease Burden and Quality of Life
Time Frame: Baseline to 6 months
  • The Myotonic Dystrophy Health Index (MDHI) is a validated disease-specific measure of patient-reported disease burden. The MDHI total score is a weighted average derived from 17 subscales. MDHI total scores range form 0-100 with 0 representing no patient-reported disease burden and 100 representing the most severe patient-reported disease burden.
  • The Individualized Neuromuscular Quality of Life Questionnaire (INQoL) is a measure of quality of life in neuromuscular disease. The INQoL summary score is a weighted average made up of 5 sub-domains. Scores range from 0-100, and can be interpreted as the percent of maximal detrimental impact on quality of life with higher scores indicating more detrimental impact.
  • The 36-Item Short Form Survey (SF-36) is a generic measure of quality of life across 8 domains. Two summary metrics are produced from the 8 domains, ranging from 0-100% with lower scores representing worse levels of functioning.
Baseline to 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Rochester

Investigators

  • Principal Investigator: Richard T. Moxley, III, MD, University of Rochester

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2011

Primary Completion (Actual)

February 1, 2017

Study Completion (Actual)

March 1, 2017

Study Registration Dates

First Submitted

July 20, 2011

First Submitted That Met QC Criteria

July 28, 2011

First Posted (Estimate)

August 1, 2011

Study Record Updates

Last Update Posted (Actual)

June 19, 2018

Last Update Submitted That Met QC Criteria

May 21, 2018

Last Verified

May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3716
  • Funding Source: FDA/OOPD (Other Grant/Funding Number: R01FD003716)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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