MyotoniaPhase 2NCT00832000
Effectiveness of Mexiletine for Treating People With Non-Dystrophic Myotonia
A Phase 2 study testing Mexiletine in people with Myotonia and Non-Dystrophic Myotonia, run by Richard Barohn, MD at 7 sites in 4 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Myotonia, Non-Dystrophic Myotonia
- What is being tested?
- Mexiletine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 59 participants
- Where
- 7 sitesin 4 countries
- Study dates
- Dec 2008to Mar 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Clinical symptoms or signs suggestive of myotonic disorders
- Presence of myotonic potentials on electromyography (EMG)
- Participant in the Non-Dystrophic Natural History study (RDCRN 5303) or a new patient with confirmed non-dystrophic myotonia
Who cannot join
- Other neurological condition that might affect the assessment of the study measurements
- Genetic confirmation of DM1 (more than 50 repeats of CTG) or DM2
- Existing cardiac conduction defects, as evidenced on EKG, including but not limited to the following conditions: malignant arrhythmia or cardiac conduction disturbances (e.g., second degree AV block, third degree AV block, or prolonged QT interval)
- Existing permanent pacemaker
- Current use of any of the following antiarrhythmic medications for a cardiac disorder: flecainide acetate, encainide, disopyramide, procainamide, quinidine, propafenone, or mexiletine
- Use of medications for myotonia, such as phenytoin and flecainide acetate, within 5 days of study entry; carbamazepine and mexiletine within 3 days of study entry; or propafenone, procainamide, disopyramide, quinidine, and encainide within 2 days of study entry
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- Use of medications that produce myotonia, which may include fibrate acid derivatives, hydroxymethylglutaryl CoA reductase inhibitors, chloroquine, and colchicines
- Kidney or liver disease
- Heart failure
- Seizure disorder
- Pregnant or breastfeeding
Trial locations and contacts
7 sites in 4 countries.
7 sites in 4 countries
United States4 sites
Brigham & Women's Hospital
Boston, Massachusetts, 02115
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
University of Kansas Medical Center
Kansas City, Kansas, 66160
University of Rochester School of Medicine & Dentistry
Rochester, New York, 14642
United Kingdom1 site
Institute of Neurology and National Hospital for Neurology
London, WC1N 3BG
About this study
Official title: Phase II Therapeutic Trial of Mexiletine in Non-Dystrophic Myotonia
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.
Read the detailed description
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.
- Conditions
- Myotonia, Non-Dystrophic Myotonia
- Being tested
- Mexiletine, Placebo
- Medical subject headings
- Myotonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MexiletineDrug
200 mg three times a day; in pill form
PlaceboDrug
Placebo three times a day; in pill form
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Participants will receive mexiletine for 4 weeks, then no intervention for 1 week, and finally placebo for 4 weeks. Receives: Drug: Mexiletine; Drug: Placebo |
| 2 | Experimental | Participants will receive placebo for 4 weeks, then no intervention for 1 week, and finally mexiletine for 4 weeks. Receives: Drug: Mexiletine; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Weeks 3-4 of each period
Secondary outcomes (13)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: The end of period 1 (week 4) and period 2 (week 9)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2009 (estimated)
- Study startDec 2008
- Primary completionMar 2011
- Study completionMar 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MyotoniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- Richard Barohn, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Richard Barohn, MD, University of Kansas Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00832000
- Sponsor's protocol ID
- 11050
- Other IDs
- FDA OPD RO1FD003454
- Status last verified
- Aug 2013
- First submitted
- 27 Jan 2009
- Last updated
- 23 Aug 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Statland JM, Bundy BN, Wang Y, Rayan DR, Trivedi JR, Sansone VA, Salajegheh MK, Venance SL, Ciafaloni E, Matthews E, Meola G, Herbelin L, Griggs RC, Barohn RJ, Hanna MG; Consortium for Clinical Investigation of Neurologic Channelopathies. Mexiletine for symptoms and signs of myotonia in nondystrophic myotonia: a randomized controlled trial. JAMA. 2012 Oct 3;308(13):1357-65. doi: 10.1001/jama.2012.12607.
PubMed 23032552
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Therapeutic Trial of Mexiletine in Non-Dystrophic Myotonia
- ClinicalTrials.gov ID
- NCT00832000
- Acronym / sponsor ID
- 11050
- Conditions
- Myotonia, Non-Dystrophic Myotonia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- Richard Barohn, MDUniversity, hospital or other
- Study start
- Dec 2008
- Primary completion
- Mar 2011 (actual)
- Study completion
- Mar 2011 (actual)
- First posted
- 29 Jan 2009 (estimated)
- Results
- Posted 11 Mar 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Mexiletine, Drug: PlaceboParticipants will receive mexiletine for 4 weeks, then no intervention for 1 week, and finally placebo for 4 weeks. |
| 2 | Experimental | Drug: Mexiletine, Drug: PlaceboParticipants will receive placebo for 4 weeks, then no intervention for 1 week, and finally mexiletine for 4 weeks. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Clinical symptoms or signs suggestive of myotonic disorders
- Presence of myotonic potentials on electromyography (EMG)
- Participant in the Non-Dystrophic Natural History study (RDCRN 5303) or a new patient with confirmed non-dystrophic myotonia
Key exclusion criteria (11 listed)
- Other neurological condition that might affect the assessment of the study measurements
- Genetic confirmation of DM1 (more than 50 repeats of CTG) or DM2
- Existing cardiac conduction defects, as evidenced on EKG, including but not limited to the following conditions: malignant arrhythmia or cardiac conduction disturbances (e.g., second degree AV block, third degree AV block, or prolonged QT interval)
- Existing permanent pacemaker
- Current use of any of the following antiarrhythmic medications for a cardiac disorder: flecainide acetate, encainide, disopyramide, procainamide, quinidine, propafenone, or mexiletine
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mexiletine200 mg three times a day; in pill form | Drug | 1, 2 |
| PlaceboPlacebo three times a day; in pill form | Drug | 1, 2 |
Primary outcome
Patient-reported Stiffness on the IVR
Time frame: Weeks 3-4 of each period
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.
13 secondary outcomes
Patient Reported Pain on the IVR
Time frame: Weeeks 3-4 of each period
Patient Reported Weakness on the IVR
Time frame: Weeks 3-4 of each period
Patient Reported Tiredness on the IVR
Time frame: Weeks 3-4 of each period
Quantitative Measure of Hand Grip Myotonia (Seconds)
Time frame: The end of period 1 (week 4) and period 2 (week 9)
Compound Motor Action Potentials After Short Exercise Test
Time frame: The end of period 1 (week 4) and period 2 (week 9)
Graded Myotonia by Needle Electromyography - Right Abductor Digiti Minimi
Time frame: The end of period 1 (week 4) and period 2 (week 9)
Clinical Hand Grip Myotonia Evaluation (Seconds)
Time frame: The end of period 1 (week 4) and the end of period 2 (week 9)
Clinical Eye Closure Myotonia Evaluation (Seconds)
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
Time frame: The end of period 1 (week 4) and period 2 (week 9)
Compound Motor Action Potentials After Long Exercise Test
Time frame: The end of period 1 (week 4) and period 2 (week 9)
Individualized Neuromuscular Quality of Life Scale - Summary Score
Time frame: The end of period 1 (week 4) and period 2 (week 9)
Short Form 36 - Physical Composite Score
Time frame: Particiapnts who experienced weakness on mexiletine in either period 1 or period 2.
Short Form 36 - Mental Composite Score
Time frame: The end of period 1 (week 4) and period 2 (week 9)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23032552Statland JM, Bundy BN, Wang Y, Rayan DR, Trivedi JR, Sansone VA, Salajegheh MK, Venance SL, Ciafaloni E, Matthews E, Meola G, Herbelin L, Griggs RC, Barohn RJ, Hanna MG; Consortium for Clinical Investigation of Neurologic Channelopathies. Mexiletine for symptoms and signs of myotonia in nondystrophic myotonia: a randomized controlled trial. JAMA. 2012 Oct 3;308(13):1357-65. doi: 10.1001/jama.2012.12607.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
7 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mexiletine in people with Myotonia and Non-Dystrophic Myotonia, run by Richard Barohn, MD at 7 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Canada, Italy, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Mar 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Patient-reported Stiffness on the IVR (time frame: Weeks 3-4 of each period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00832000, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Aug 2013.