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Clinical Efficacy Trial of Mexiletine for Myotonic Dystrophy Type 1

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ClinicalTrials.gov Identifier: NCT01406873
Recruitment Status : Completed
First Posted : August 1, 2011
Results First Posted : March 29, 2018
Last Update Posted : June 19, 2018
Sponsor:
Information provided by (Responsible Party):
Chad Heatwole, University of Rochester

Tracking Information
First Submitted Date  ICMJE July 20, 2011
First Posted Date  ICMJE August 1, 2011
Results First Submitted Date  ICMJE March 1, 2018
Results First Posted Date  ICMJE March 29, 2018
Last Update Posted Date June 19, 2018
Study Start Date  ICMJE June 2011
Actual Primary Completion Date February 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 1, 2018)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 28, 2011)
Ambulation [ Time Frame: 6 months ]
Change History Complete list of historical versions of study NCT01406873 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 21, 2018)
  • 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.
  • 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).
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 28, 2011)
  • The Number of Study Participants Who Safely Tolerated mexiletine [ Time Frame: 6 months ]
    Safety and tolerability are monitored by interval laboratory studies, Holter monitoring, resting echocardiograms, dula energy x-ray absorptiometry (DEXA)studies, and physical examinations. The participants have three in-person evaluations at the University of Rochester Clinical Research Center (Months 0, 3, and 6) and telephone evaluations every 2 weeks. Patients complete side effects diaries to record any adverse events in the interval time between the in-person evaluations.
  • Myotonia [ Time Frame: 6 months ]
  • Muscle function and strength [ Time Frame: 6 months ]
  • Cardiac conduction [ Time Frame: 6 months ]
  • Quality of Life [ Time Frame: 6 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Clinical Efficacy Trial of Mexiletine for Myotonic Dystrophy Type 1
Official Title  ICMJE A Randomized, Placebo Controlled, Clinical Efficacy Trial of Mexiletine for Myotonic Dystrophy Type-1 (DM1)
Brief Summary 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).
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Myotonic Dystrophy
Intervention  ICMJE
  • Drug: Mexiletine
    150 mg/kg Mexiletine capsules taken by mouth, three times daily for 6 months
    Other Name: Generic name: mexiletine hydrochloride
  • Drug: Placebo
    150 mg/kg placebo capsules taken by mouth, three times daily for 6 months
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Mexiletine
  • 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.
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 12, 2016)
42
Original Estimated Enrollment  ICMJE
 (submitted: July 28, 2011)
40
Actual Study Completion Date  ICMJE March 2017
Actual Primary Completion Date February 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01406873
Other Study ID Numbers  ICMJE 3716
Funding Source: FDA/OOPD ( Other Grant/Funding Number: R01FD003716 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Chad Heatwole, University of Rochester
Study Sponsor  ICMJE University of Rochester
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Richard T. Moxley, III, MD University of Rochester
PRS Account University of Rochester
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP