| Mexiletine for symptoms and signs of myotonia in nondystrophic myotonia: a randomized controlled trial. | |
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MedLine Citation:
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PMID: 23032552 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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CONTEXT: Nondystrophic myotonias (NDMs) are rare diseases caused by mutations in skeletal muscle ion channels. Patients experience delayed muscle relaxation causing functionally limiting stiffness and pain. Mexiletine-induced sodium channel blockade reduced myotonia in small studies; however, as is common in rare diseases, larger studies of safety and efficacy have not previously been considered feasible. OBJECTIVE: To determine the effects of mexiletine for symptoms and signs of myotonia in patients with NDMs. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled 2-period crossover study at 7 neuromuscular referral centers in 4 countries of 59 patients with NDMs conducted between December 23, 2008, and March 30, 2011, as part of the National Institutes of Health-funded Rare Disease Clinical Research Network. INTERVENTION: Oral 200-mg mexiletine or placebo capsules 3 times daily for 4 weeks, followed by the opposite intervention for 4 weeks, with 1-week washout in between. MAIN OUTCOME MEASURES: Patient-reported severity score of stiffness recorded on an interactive voice response (IVR) diary (scale of 1 = minimal to 9 = worst ever experienced). Secondary end points included IVR-reported changes in pain, weakness, and tiredness; clinical myotonia assessment; quantitative measure of handgrip myotonia; and Individualized Neuromuscular Quality of Life summary quality of life score (INQOL-QOL, percentage of maximal detrimental impact). RESULTS: Mexiletine significantly improved patient-reported severity score stiffness on the IVR diary. Because of a statistically significant interaction between treatment and period for this outcome, primary end point is presented by period (period 1 means were 2.53 for mexiletine and 4.21 for placebo; difference, -1.68; 95% CI, -2.66 to -0.706; P < .001; period 2 means were 1.60 for mexiletine and 5.27 for placebo; difference, -3.68; 95% CI, -3.85 to -0.139; P = .04). Mexiletine improved the INQOL-QOL score (mexiletine, 14.0 vs placebo, 16.7; difference, -2.69; 95% CI, -4.07 to -1.30; P < .001) and decreased handgrip myotonia on clinical examination (mexiletine, 0.164 seconds vs placebo, 0.494 seconds; difference, -0.330; 95% CI, -0.633 to -0.142; P < .001). The most common adverse effect was gastrointestinal (9 mexiletine and 1 placebo). Two participants experienced transient cardiac effects that did not require stopping the study (1 in each group). One serious adverse event was determined to be not study related. CONCLUSION: In this preliminary study of patients with NDMs, the use of mexiletine compared with placebo resulted in improved patient-reported stiffness over 4 weeks of treatment, despite some concern about the maintenance of blinding. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00832000. |
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Authors:
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Jeffrey M Statland; Brian N Bundy; Yunxia Wang; Dipa Raja Rayan; Jaya R Trivedi; Valeria A Sansone; Mohammad K Salajegheh; Shannon L Venance; Emma Ciafaloni; Emma Matthews; Giovanni Meola; Laura Herbelin; Robert C Griggs; Richard J Barohn; Michael G Hanna; |
Publication Detail:
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Type: Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: JAMA : the journal of the American Medical Association Volume: 308 ISSN: 1538-3598 ISO Abbreviation: JAMA Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-03 Completed Date: 2012-10-09 Revised Date: 2013-04-26 |
Medline Journal Info:
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Nlm Unique ID: 7501160 Medline TA: JAMA Country: United States |
Other Details:
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Languages: eng Pagination: 1357-65 Citation Subset: AIM; IM |
Affiliation:
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Department of Neurology, University of Rochester Medical Center, Rochester, New York, USA. |
| Data Bank Information | |
Bank Name/Acc. No.:
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ClinicalTrials.gov/NCT00832000 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Oral Adolescent Adult Aged Anti-Arrhythmia Agents / adverse effects, therapeutic use* Cross-Over Studies Double-Blind Method Female Humans Male Mexiletine / adverse effects, therapeutic use* Middle Aged Muscle, Skeletal / physiopathology Myotonia / drug therapy* Pain / drug therapy, etiology Quality of Life Severity of Illness Index Sodium Channels / drug effects Young Adult |
| Grant Support | |
ID/Acronym/Agency:
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R01 FD 003454/FD/FDA HHS; T32 NS07338-20/NS/NINDS NIH HHS; U54 NS059065-05S1/NS/NINDS NIH HHS; UL1 RR 024160/RR/NCRR NIH HHS; UL1 RR 024982/RR/NCRR NIH HHS; UL1 RR 033179/RR/NCRR NIH HHS; UL1 RR024160/RR/NCRR NIH HHS; UL1 RR033179/RR/NCRR NIH HHS; UL1 TR 000001/TR/NCATS NIH HHS; UL1 TR000001/TR/NCATS NIH HHS; //Medical Research Council |
| Chemical | |
Reg. No./Substance:
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0/Anti-Arrhythmia Agents; 0/Sodium Channels; 31828-71-4/Mexiletine |
| Investigator | |
Investigator/Affiliation:
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Richard J Barohn / ; Yunxia Wang / ; Jeffrey Statland / ; Mazen Dimachkie / ; Laura Herbelin / ; JoAnn Miller / ; Rhea Pimental / ; Jaya Trivedi / ; Nina Gorham / ; Rhonda McLin / ; Vivian Gonzales / ; Mohammad Kian Salajegheh / ; Anthony A Amato / ; Kristen Roe / ; Samantha Chused / ; Essa Kayd / ; Shannon Venance / ; Angelica Hahn / ; Wilma Koopman / ; Jennifer Verheyden / ; Ashley Ten Haaf / ; Christine Piechowicz / ; Robert C Griggs / ; Emma Ciafaloni / ; Paul Twydell / ; Katherine Aronson / ; Kimberly Hart / ; Patricia Smith / ; Barbara Herr / ; Kate Eichinger / ; Shree Pandya / ; Stephen Bean / ; Araya Puwanant / ; Quing Ke / ; Jill Scheltz / ; Laura Whitesell / ; Michael Hanna / ; Dipa L Raja Rayan / ; Emma Matthews / ; Gisela Barreto / ; Veronica Tan / ; James Burge / ; Elizabeth Dewar / ; Daleen Lopez-Begum / ; Richa Sud / ; Andrea Haworth / ; Samuel McCall / ; Valeria Sansone / ; Giovanni Meola / ; Alice Zanolini / ; Matteo Ciocca / ; Brian Bundy / ; Jeffrey Krischer / ; Holly Ruhlig / ; Joseph Gomes / ; Rachel Richesson / ; Renee Leduc / ; Jennifer Pilger / ; John W Day / ; Robert T Leshner / ; Todd A Mackenzie / ; Kathryn Wagner / ; Joanne C Odenkirchen / ; Randy Stewart / |
| Comments/Corrections | |
Comment In:
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JAMA. 2012 Oct 3;308(13):1377-8
[PMID:
23032555
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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