Back to resultsClinical Efficacy Trial of Mexiletine for Myotonic Dystrophy Type 1
Primary Purpose
Myotonic Dystrophy
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Mexiletine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Myotonic Dystrophy focused on measuring Myotonic Dystrophy, Myotonic Dystrophy Type 1 (DM1), Muscular Dystrophy, Mexiletine
Eligibility Criteria
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
Sites / Locations
- University of Rochester Medical Center, Department of Neurology
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Mexiletine
Sugar pill
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Mean Change From Baseline in Ambulation Using the 6 Minute Walk Distance
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.
Secondary Outcome Measures
Percentage of Participants That Had a Dose Reduction or a Study Drug Withdrawal or Suspension Over 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
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
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
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01406873
Brief Title
Clinical Efficacy Trial of Mexiletine for Myotonic Dystrophy Type 1
Official Title
A Randomized, Placebo Controlled, Clinical Efficacy Trial of Mexiletine for Myotonic Dystrophy Type-1 (DM1)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
June 2011 (undefined)
Primary Completion Date
February 2017 (Actual)
Study Completion Date
March 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Rochester
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myotonic Dystrophy
Keywords
Myotonic Dystrophy, Myotonic Dystrophy Type 1 (DM1), Muscular Dystrophy, Mexiletine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
42 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Mexiletine
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Sugar pill
Arm Type
Placebo Comparator
Arm Description
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 Type
Drug
Intervention Name(s)
Mexiletine
Other Intervention Name(s)
Generic name: mexiletine hydrochloride
Intervention Description
150 mg/kg Mexiletine capsules taken by mouth, three times daily for 6 months
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
150 mg/kg placebo capsules taken by mouth, three times daily for 6 months
Primary Outcome Measure Information:
Title
Mean Change From Baseline in Ambulation Using the 6 Minute Walk Distance
Description
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.
Time Frame
Baseline to 6 months
Secondary Outcome Measure Information:
Title
Percentage of Participants That Had a Dose Reduction or a Study Drug Withdrawal or Suspension Over 6 Months
Description
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.
Time Frame
6 months
Title
Mean Change From Baseline in Quantitative Measure of Hand Grip Myotonia
Description
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).
Time Frame
Baseline to 6 months
Title
Mean Change From Baseline in Manual Muscle Testing (MMT) Score
Description
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.
Time Frame
Baseline to 6 months
Title
Mean Change From Baseline in PR, QRS, and QTc Intervals, and Average Minimum Heart Rate (HR) Via Electrocardiogram (ECG) Monitoring
Description
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.
Time Frame
Baseline to 6 Months
Title
Mean Change From Baseline in Patient-Reported Disease Burden and Quality of Life
Description
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.
Time Frame
Baseline to 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard T. Moxley, III, MD
Organizational Affiliation
University of Rochester
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Rochester Medical Center, Department of Neurology
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
20439846
Citation
Logigian EL, Martens WB, Moxley RT 4th, McDermott MP, Dilek N, Wiegner AW, Pearson AT, Barbieri CA, Annis CL, Thornton CA, Moxley RT 3rd. Mexiletine is an effective antimyotonia treatment in myotonic dystrophy type 1. Neurology. 2010 May 4;74(18):1441-8. doi: 10.1212/WNL.0b013e3181dc1a3a.
Results Reference
background
PubMed Identifier
17587223
Citation
Moxley RT 3rd, Logigian EL, Martens WB, Annis CL, Pandya S, Moxley RT 4th, Barbieri CA, Dilek N, Wiegner AW, Thornton CA. Computerized hand grip myometry reliably measures myotonia and muscle strength in myotonic dystrophy (DM1). Muscle Nerve. 2007 Sep;36(3):320-8. doi: 10.1002/mus.20822.
Results Reference
background
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Clinical Efficacy Trial of Mexiletine for Myotonic Dystrophy Type 1
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