A Phase 2 interventional study of Mexiletine and Placebo in Myotonia and Non-Dystrophic Myotonia, sponsored by Richard Barohn, MD. Completed at 7 sites in 4 countries. Open to participants aged 16 Years and older. Per ClinicalTrials.gov, last updated 2013-08-23.
Sponsored by Richard Barohn, MD · Phase 2, Interventional, and Treatment
Nondystrophic myotonias (NDM) are neuromuscular disorders caused by genetic abnormalities in certain muscle cell membrane proteins. The proteins affect muscle contraction. Individuals with NDM experience limited muscle relaxation, which then can cause pain, weakness, incoordination, and impaired physical activity and function. Because NDM is very rare, information on the best way to treat people with the disorders is lacking, and there are no FDA-approved therapies. The purpose of this study is to determine the effectiveness of the medication mexiletine in treating people with NDM.
NDM are neuromuscular disorders that are caused by mutations in skeletal muscle ion channels, usually voltage-dependent sodium and chloride channels. The poorly functioning channels result in impaired muscle relaxation after contraction, which is also called myotonia. Mexiletine is an antiarrhythmic medication that has a high affinity for muscle sodium channels and may have the ability to correct delayed inactivation of sodium channels. In case reports and single-blind clinical trials, mexiletine was shown to reduce symptoms of myotonia. Currently, there is no standard strategy for treating people with NDM, and effective treatment options are needed. This study will determine the effectiveness of mexiletine in treating people with NDM.
Participation in this study will last 9 weeks and will involve two separate 4-week treatment periods, with a 1-week washout period between them. During the first treatment period, participants will be randomly assigned to receive either mexiletine or placebo, both of which will be taken three times a day. This will be followed by 1 week of no treatment. During the second treatment period, participants will receive whichever treatment they did not receive initially and will follow the same dosing schedule.
Participants will attend five study visits that will occur at screening and Weeks 0, 4, 5, and 9. Screening will include blood and urine sampling, electrocardiography (EKG), and a medical history. The remaining visits will include a physical examination, a grip test, exercise tests, nerve conduction tests, blood sampling, questionnaires, and electromyography (EMG). EKG will be repeated at Weeks 4, 5, and 9. Throughout the study, participants will phone in daily to report their symptoms. There will be no follow-up visits.
Funded by FDAOPD RO1 0003454.
25 studies on the registry are indexed under Myotonia; 8 are open to participants now.
This study's enrollment of 59 is above the median of 35 across 17 interventional studies indexed under Myotonia.
Browse Myotonia studies →Richard Barohn, MD is the lead sponsor of 4 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Participants will receive mexiletine for 4 weeks, then no intervention for 1 week, and finally placebo for 4 weeks.
Drug: Mexiletine · Drug: Placebo
Participants will receive placebo for 4 weeks, then no intervention for 1 week, and finally mexiletine for 4 weeks.
Drug: Mexiletine · Drug: Placebo
200 mg three times a day; in pill form
Placebo three times a day; in pill form
Patient-reported Stiffness on the IVR
Stiffness measured on a 1-9 scale, 1 being minimal, 9 the worst ever experienced. 0=no symptom reported. For analysis the average severity of stiffness for each participant was calculated from daily calls made in weeks 3-4 of each period.
Time frame: Weeks 3-4 of each period
Patient Reported Pain on the IVR
Pain measured on a 1-9 scale, 1 being minimal, 9 the worst ever experienced. 0=no symptom reported. For analysis the average severity of pain for each participant was calculated from daily calls made in weeks 3-4 of each period.
Time frame: Weeeks 3-4 of each period
Patient Reported Weakness on the IVR
Weakness measured on a 1-9 scale, 1 being minimal, 9 the worst ever experienced. 0=no symptom reported. For analysis the average severity of weakness for each participant was calculated from daily calls made in weeks 3-4 of each period.
Time frame: Weeks 3-4 of each period
Patient Reported Tiredness on the IVR
Tiredness measured on a 1-9 scale, 1 being minimal, 9 the worst ever experienced. 0=no symptom reported. For analysis the average severity of tiredness for each participant was calculated from daily calls made in weeks 3-4 of each period.
Time frame: Weeks 3-4 of each period
Quantitative Measure of Hand Grip Myotonia (Seconds)
Maximum voluntary contractions following forced right hand grip were recorded and the time to relax from 90% to 5% of average maximal force was determined using automated analysis software.
Time frame: The end of period 1 (week 4) and period 2 (week 9)
Compound Motor Action Potentials After Short Exercise Test
The maximal post-exercise compound muscle action potential (CMAP) after short periods of exercise as a percent of the baseline measurement.
Time frame: The end of period 1 (week 4) and period 2 (week 9)
Graded Myotonia by Needle Electromyography - Right Abductor Digiti Minimi
Measured the amount of myotonia present on needle exam by assigning a number 1-3, with 1 being minimal amount of myotonia on needle stick and 3 being maximal amount of myotonia present on needle stick.
Time frame: The end of period 1 (week 4) and period 2 (week 9)
Clinical Hand Grip Myotonia Evaluation (Seconds)
The time to open the fist after a forced handgrip as measured on a stopwatch.
Time frame: The end of period 1 (week 4) and the end of period 2 (week 9)
Clinical Eye Closure Myotonia Evaluation (Seconds)
Time to open the eyes after forced eye closure as measured on a stopwatch.
Time frame: The end of period 1 (week 4) and the end of period 2 (week 9)
Graded Myotonia by Needle Electromyography - Right Tibialis Anterior
Measured the amount of myotonia present on needle exam by assigning a number 1-3, with 1 being minimal amount of myotonia on needle stick and 3 being maximal amount of myotonia present on needle stick.
Time frame: The end of period 1 (week 4) and period 2 (week 9)
Compound Motor Action Potentials After Long Exercise Test
Compound muscle action potential (CMAP) after long periods of exercise as a percentage of baseline.
Time frame: The end of period 1 (week 4) and period 2 (week 9)
Individualized Neuromuscular Quality of Life Scale - Summary Score
Quality of life scale for patinets with neuromuscular disorders. The INQoL summary score is a weighted average made up of 5 subdomains (activities, social relationships, independence, emotions, and body image) which document the impact of a disease on a patients' quality of life. Scores range from 0-100, and can be interpreted as the percent of maximal detrimental impact on quality of life. A higher score indicates more detrimental impact.
Time frame: The end of period 1 (week 4) and period 2 (week 9)
Short Form 36 - Physical Composite Score
The SF-36 is a standard quality of life instrument. The physical composite score represents the the physical burden on quality of life and is a summary of questions related to physical impact of a disease or condition (physical function, role physical, bodily pain, and general health). The score is nomralized to the population and ranges from 0-100, with the US normal value of 50. A lower score represents a greater impact of quality of life.
Time frame: Particiapnts who experienced weakness on mexiletine in either period 1 or period 2.
Short Form 36 - Mental Composite Score
The SF-36 is a standard quality of life instrument. The mental composite score represents the the mental burden on quality of life and is a summary of questions related to mental impact of a disease or condition (mental function, role emotional, vitality, and mental health). The score is nomralized to the population and ranges from 0-100, with the US normal value of 50. A lower score represents a greater impact of quality of life.
Time frame: The end of period 1 (week 4) and period 2 (week 9)
Eligible participants were at least 16 years of age, had clinical symptoms or signs of NDM, and myotonic potentials on electromyography. Participants were either enrolled in the CINCH NDM Natural History Study, or a new patient with genetically confirmed NDM, or with clinical features of NDM but negative myotonic dystrophy DNA testing.
| Milestone | Mexiletine Then Placebo | Placebo Then Mexiletine |
|---|---|---|
| Started | 29 | 30 |
| Crossed over to opposite intervention | 25 | 29 |
| Completed | 23 | 29 |
| Not completed | 6 | 1 |
| Withdrew: Adverse event | 2 | 0 |
| Withdrew: Withdrawal by subject | 1 | 0 |
| Withdrew: No calls to ivr in either period | 1 | 1 |
| Withdrew: No calls to ivr in period 2 | 2 | 0 |
Stiffness measured on a 1-9 scale, 1 being minimal, 9 the worst ever experienced. 0=no symptom reported. For analysis the average severity of stiffness for each participant was calculated from daily calls made in weeks 3-4 of each period.
| units on a scale | Mexiletine - Period 1 | Placebo - Period 1 | Mexiletine - Period 2 | Placebo - Period 2 |
|---|---|---|---|---|
| Patient-reported Stiffness on the IVR | 2.53 (1.80 to 3.17) | 4.21 (3.40 to 5.20) | 1.60 (1.04 to 2.20) | 5.27 (4.44 to 6.27) |
Pain measured on a 1-9 scale, 1 being minimal, 9 the worst ever experienced. 0=no symptom reported. For analysis the average severity of pain for each participant was calculated from daily calls made in weeks 3-4 of each period.
| units on a scale | Mexiletine | Placebo |
|---|---|---|
| Patient Reported Pain on the IVR | 1.54 (0.924 to 2.13) | 3.17 (2.43 to 3.93) |
Weakness measured on a 1-9 scale, 1 being minimal, 9 the worst ever experienced. 0=no symptom reported. For analysis the average severity of weakness for each participant was calculated from daily calls made in weeks 3-4 of each period.
| units on a scale | Mexiletine | Placebo |
|---|---|---|
| Patient Reported Weakness on the IVR | 1.96 (1.42 to 2.63) | 3.22 (2.52 to 3.98) |
Tiredness measured on a 1-9 scale, 1 being minimal, 9 the worst ever experienced. 0=no symptom reported. For analysis the average severity of tiredness for each participant was calculated from daily calls made in weeks 3-4 of each period.
| units on a scale | Mexiletine | Placebo |
|---|---|---|
| Patient Reported Tiredness on the IVR | 2.90 (2.12 to 3.68) | 3.82 (3.03 to 4.53) |
Maximum voluntary contractions following forced right hand grip were recorded and the time to relax from 90% to 5% of average maximal force was determined using automated analysis software.
| seconds | Mexiletine | Placebo |
|---|---|---|
| Quantitative Measure of Hand Grip Myotonia (Seconds) | 0.321 (0.274 to 0.370) | 0.429 (0.365 to 0.517) |
The maximal post-exercise compound muscle action potential (CMAP) after short periods of exercise as a percent of the baseline measurement.
| percentage of baseline CMAP amplitude | Mexiletine | Placebo |
|---|---|---|
| Compound Motor Action Potentials After Short Exercise Test | 83.1 (77.5 to 88.4) | 78.6 (71.9 to 84.7) |
Measured the amount of myotonia present on needle exam by assigning a number 1-3, with 1 being minimal amount of myotonia on needle stick and 3 being maximal amount of myotonia present on needle stick.
| units on a scale | Mexiletine | Placebo |
|---|---|---|
| Graded Myotonia by Needle Electromyography - Right Abductor Digiti Minimi | 2.05 (1.75 to 2.33) | 2.62 (2.39 to 2.86) |
The time to open the fist after a forced handgrip as measured on a stopwatch.
| Seconds | Mexiletine | Placebo |
|---|---|---|
| Clinical Hand Grip Myotonia Evaluation (Seconds) | 0.164 (0.0858 to .294) | 0.494 (0.281 to 0.872) |
Time to open the eyes after forced eye closure as measured on a stopwatch.
| Seconds | Mexiletine | Placebo |
|---|---|---|
| Clinical Eye Closure Myotonia Evaluation (Seconds) | 0.161 (0.0704 to 0.314) | 0.474 (0.261 to 0.871) |
Measured the amount of myotonia present on needle exam by assigning a number 1-3, with 1 being minimal amount of myotonia on needle stick and 3 being maximal amount of myotonia present on needle stick.
| units on a scale | Mexiletine | Placebo |
|---|---|---|
| Graded Myotonia by Needle Electromyography - Right Tibialis Anterior | 2.07 (1.73 to 2.37) | 2.54 (2.28 to 2.76) |
Compound muscle action potential (CMAP) after long periods of exercise as a percentage of baseline.
| percentage of baseline CMAP amplitude | Mexiletine | Placebo |
|---|---|---|
| Compound Motor Action Potentials After Long Exercise Test | 81.8 (76.8 to 87.0) | 80.1 (74.7 to 86.4) |
Quality of life scale for patinets with neuromuscular disorders. The INQoL summary score is a weighted average made up of 5 subdomains (activities, social relationships, independence, emotions, and body image) which document the impact of a disease on a patients' quality of life. Scores range from 0-100, and can be interpreted as the percent of maximal detrimental impact on quality of life. A higher score indicates more detrimental impact.
| units on a scale | Mexiletine | Placebo |
|---|---|---|
| Individualized Neuromuscular Quality of Life Scale - Summary Score | 14.0 (11.6 to 16.5) | 16.7 (14.0 to 19.4) |
The SF-36 is a standard quality of life instrument. The physical composite score represents the the physical burden on quality of life and is a summary of questions related to physical impact of a disease or condition (physical function, role physical, bodily pain, and general health). The score is nomralized to the population and ranges from 0-100, with the US normal value of 50. A lower score represents a greater impact of quality of life.
| units on a scale | Mexiletine | Placebo |
|---|---|---|
| Short Form 36 - Physical Composite Score | 44.8 (41.9 to 47.4) | 39.2 (35.9 to 41.9) |
The SF-36 is a standard quality of life instrument. The mental composite score represents the the mental burden on quality of life and is a summary of questions related to mental impact of a disease or condition (mental function, role emotional, vitality, and mental health). The score is nomralized to the population and ranges from 0-100, with the US normal value of 50. A lower score represents a greater impact of quality of life.
| units on a scale | Mexiletine - Period 1 | Placebo - Period 1 | Mexiletine - Period 2 | Placebo - Period 2 |
|---|---|---|---|---|
| Short Form 36 - Mental Composite Score | 47.4 (44.0 to 50.2) | 47.7 (44.2 to 51.3) | 53.1 (50.3 to 55.8) | 42.7 (36.8 to 48.3) |
Collected over Data was collected over a 3 year period. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Mexiletine Treatment | — | 1/57 (1.8%) | 24/57 (42.1%) |
| Placebo Treatment | — | 0/57 (0%) | 11/57 (19.3%) |
| Event | Mexiletine Treatment | Placebo Treatment |
|---|---|---|
| Drug withdrawalPsychiatric disorders | 1/1 | — |
| Event | Mexiletine Treatment | Placebo Treatment |
|---|---|---|
| GastrointestinalGastrointestinal disorders | 9/57 | 1/57 |
| NeurologicNervous system disorders | 5/57 | 1/57 |
| PainGeneral disorders | 4/57 | 0/57 |
| ConstitutionalGeneral disorders | 3/57 | 0/57 |
| InfectionInfections and infestations | 1/57 | 3/57 |
| Dermatologic/skinSkin and subcutaneous tissue disorders | 1/57 | 2/57 |
| Musculosketetal/soft tissueMusculoskeletal and connective tissue disorders | 0/57 | 2/57 |
| LymphaticsBlood and lymphatic system disorders | 0/57 | 1/57 |
| CardiacCardiac disorders | 1/57 | 1/57 |
| Age, Categorical(Participants) | All Study Participants |
|---|---|
| <=18 years | 1 |
| Between 18 and 65 years | 56 |
| >=65 years | 2 |
| Age Continuous(years) | All Study Participants |
|---|---|
| Mean | 42.9 ± 25 |
| Sex: Female, Male(Participants) | All Study Participants |
|---|---|
| Female | 26 |
| Male | 33 |
| Region of Enrollment(participants) | All Study Participants |
|---|---|
| United States | 31 |
| Canada | 4 |
| United Kingdom | 12 |
| Italy | 12 |
This study is completed, as verified in Aug 2013. You cannot join it, but the record below documents what was studied.
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