Effectiveness of Mexiletine for Treating People With Non-Dystrophic Myotonia

NCT ID: NCT00832000

Last Updated: 2013-08-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2011-03-31

Brief 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 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.

Conditions

Myotonia; Non-Dystrophic Myotonia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

1

Participants will receive mexiletine for 4 weeks, then no intervention for 1 week, and finally placebo for 4 weeks.

Group Type: EXPERIMENTAL

Mexiletine

Intervention Type: DRUG

200 mg three times a day; in pill form

Placebo

Intervention Type: DRUG

Placebo three times a day; in pill form

2

Participants will receive placebo for 4 weeks, then no intervention for 1 week, and finally mexiletine for 4 weeks.

Group Type: EXPERIMENTAL

Mexiletine

Intervention Type: DRUG

200 mg three times a day; in pill form

Placebo

Intervention Type: DRUG

Placebo three times a day; in pill form

Interventions

Mexiletine

200 mg three times a day; in pill form

Intervention Type: DRUG

Placebo

Placebo three times a day; in pill form

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• 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

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Richard Barohn, MD

OTHER

Sponsor Role: lead

Responsible Party

Richard Barohn, MD

Gertrude and Dewey Zeigler Professor of Neurology and Chair

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

University of Kansas Medical Center

Kansas City, Kansas, United States

Brigham & Women's Hospital

Boston, Massachusetts, United States

University of Rochester School of Medicine & Dentistry

Rochester, New York, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

London Health Sciences Center

London, Ontario, Canada

University of Milan

Milan, , Italy

Institute of Neurology and National Hospital for Neurology

London, , United Kingdom

Countries

United States; Canada; Italy; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 23032552 (View on PubMed)

Other Identifiers

FDA OPD RO1FD003454

Identifier Type: -

Identifier Source: secondary_id

11050

Identifier Type: -

Identifier Source: org_study_id

NCT00721942

Identifier Type: -

Identifier Source: nct_alias