Effectiveness of Mexiletine for Treating People With Non-Dystrophic Myotonia

NCT00832000 | Completed Phase 2 Results DMC

• 2 other identifiers: 11050FDA OPD RO1FD003454
• Study Type: interventional
• Target: 59
• Locations: 4 countries
• Sites: 7

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.

Conditions

Myotonia; Non-Dystrophic Myotonia

Outcome Measures

Primary Outcomes (1)

• 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.

  Weeks 3-4 of each period

Secondary Outcomes (13)

• Patient Reported Pain on the IVR

  Weeeks 3-4 of each period

• Patient Reported Weakness on the IVR

  Weeks 3-4 of each period

• Patient Reported Tiredness on the IVR

  Weeks 3-4 of each period

• Quantitative Measure of Hand Grip Myotonia (Seconds)

  The end of period 1 (week 4) and period 2 (week 9)

• Compound Motor Action Potentials After Short Exercise Test

  The end of period 1 (week 4) and period 2 (week 9)

Study Arms (2)

1

EXPERIMENTAL

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

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.

Drug: Mexiletine; Drug: Placebo

Interventions

Mexiletine DRUG

200 mg three times a day; in pill form

1; 2

Placebo DRUG

Placebo three times a day; in pill form

1; 2

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Richard Barohn, MD: lead

Study Sites (7)

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Rochester School of Medicine & Dentistry

Rochester, New York, 14642, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

London Health Sciences Center

London, Ontario, N6A 5A5, Canada

Location

University of Milan

Milan, Italy

Location

Institute of Neurology and National Hospital for Neurology

London, WC1N 3BG, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 23032552 DERIVED

MeSH Terms

Conditions

Myotonia

Interventions

Mexiletine

Condition Hierarchy (Ancestors)

Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Phenyl Ethers; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Richard J. Barohn, MD
• Organization: University of Kansas Medical Center

rbarohn@kumc.edu

913-588-6095

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Gertrude and Dewey Zeigler Professor of Neurology and Chair

Study Record Dates

• First Submitted: January 27, 2009
• First Posted: January 29, 2009
• Study Start: December 1, 2008
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: August 23, 2013
• Results First Posted: March 11, 2013

Record last verified: 2013-08

Locations

IT (1); US (4); CA (1); GB (1)