Effectiveness of Mexiletine for Treating People With Non-Dystrophic Myotonia - Full Text View

Sponsors and Collaborators:	Office of Rare Diseases (ORD) Rare Diseases Clinical Research Network
Information provided by:	Office of Rare Diseases (ORD)
ClinicalTrials.gov Identifier:	NCT00832000

Purpose

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.

Condition	Intervention	Phase
Myotonia Non-Dystrophic Myotonia	Drug: Mexiletine Drug: Placebo	Phase II

Drug Information available for: Mexiletine Mexiletine hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Outcomes Assessor), Placebo Control, Crossover Assignment, Efficacy Study
Official Title:	Phase II Therapeutic Trial of Mexiletine in Non-Dystrophic Myotonia

Further study details as provided by Office of Rare Diseases (ORD):

Primary Outcome Measures:

Patient-assessed stiffness [ Time Frame: Measured at Weeks 2, 3, 7, and 8 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Patient-assessed pain, weakness, and fatigue [ Time Frame: Measured at Weeks 0, 4, 5, and 9 ] [ Designated as safety issue: No ]
Clinical myotonia [ Time Frame: Measured at Weeks 0, 4, 5, and 9 ] [ Designated as safety issue: No ]
Quality of life [ Time Frame: Measured at Weeks 0, 4, 5, and 9 ] [ Designated as safety issue: No ]
Quantitative measure of grip myotonia [ Time Frame: Measured at Weeks 0, 4, 5, and 9 ] [ Designated as safety issue: No ]
Compound motor action potentials after short and long exercise tests [ Time Frame: Measured at Weeks 0, 4, 5, and 9 ] [ Designated as safety issue: No ]
Grading of myotonia on needle electromyography (EMG) [ Time Frame: Measured at Weeks 0, 4, 5, and 9 ] [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	December 2008
Estimated Study Completion Date:	January 2011
Estimated Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Participants will receive mexiletine for 4 weeks, then no intervention for 1 week, and finally placebo for 4 weeks.	Drug: Mexiletine 200 mg three times a day; in pill form Drug: Placebo Placebo three times a day; in pill form
2: Experimental Participants will receive placebo for 4 weeks, then no intervention for 1 week, and finally mexiletine for 4 weeks.	Drug: Mexiletine 200 mg three times a day; in pill form Drug: Placebo Placebo three times a day; in pill form

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.

Eligibility

Ages Eligible for Study:	16 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00832000

Contacts

Contact: Laura Herbelin, BS

913-588-5095

lherbelin@kumc.edu

Locations

United States, Kansas
University of Kansas Medical Center	Recruiting
Kansas City, Kansas, United States, 66160
Principal Investigator: Richard Barohn, MD
Sub-Investigator: Yunxia Wang, MD
Sub-Investigator: Mazen Dimachkie, MD
United States, Massachusetts
Brigham & Women's Hospital	Not yet recruiting
Boston, Massachusetts, United States, 02115
Principal Investigator: Mohammad Kian Salajegheh, MD
Sub-Investigator: Anthony Amato, MD
United States, New York
University of Rochester School of Medicine & Dentistry	Not yet recruiting
Rochester, New York, United States, 14642
Principal Investigator: Robert C. Griggs, MD
Sub-Investigator: Paul Twydell, DO
Sub-Investigator: Shree Pandya, MS
United States, Texas
University of Texas Southwestern Medical Center	Recruiting
Dallas, Texas, United States, 75390
Principal Investigator: Jaya Trivedi, MD
Sub-Investigator: Gail Wolfe, MD
Sub-Investigator: Sharon Nations, MD
Canada, Ontario
London Health Sciences Center	Not yet recruiting
London, Ontario, Canada, N6A 5A5
Principal Investigator: Shannon Venance, MD
Sub-Investigator: Angelika Hahn, MD
United Kingdom
Institute of Neurology and National Hospital for Neurology	Not yet recruiting
London, United Kingdom, WC1N 3BG
Principal Investigator: Michael Hanna, MD
Sub-Investigator: Emma Matthews, MD

Sponsors and Collaborators

Office of Rare Diseases (ORD)

Rare Diseases Clinical Research Network

More Information

No publications provided

Responsible Party:	University of Kansas Medical Center ( Richard Barohn, MD )
Study ID Numbers:	RDCRN 5306
Study First Received:	January 27, 2009
Last Updated:	January 27, 2009
ClinicalTrials.gov Identifier:	NCT00832000 History of Changes
Health Authority:	United States: Food and Drug Administration

Study placed in the following topic categories:

Signs and Symptoms
Nondystrophic Myotonia
Neurologic Manifestations
Mexiletine

Cardiovascular Agents
Anti-Arrhythmia Agents
Myotonia

Additional relevant MeSH terms:

Signs and Symptoms
Neuromuscular Manifestations
Therapeutic Uses
Nervous System Diseases
Neurologic Manifestations

Mexiletine
Cardiovascular Agents
Anti-Arrhythmia Agents
Myotonia
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 06, 2009