OBJECTIVE: To assess mexiletine's long-term safety and effect on 6-minute walk distance in a well-defined cohort of patients with myotonic dystrophy type 1 (DM1). METHODS: We performed a randomized, double-blind, placebo-controlled trial of mexiletine (150 mg 3 times daily) to evaluate its efficacy and safety in a homogenous cohort of adult ambulatory patients with DM1. The primary outcome was change in 6-minute walk distance at 6 months. Secondary outcomes included changes in hand grip myotonia, strength, swallowing, forced vital capacity, lean muscle mass, Myotonic Dystrophy Health Index scores, and 24-hour Holter and ECG results at 3 and 6 months. RESULTS: Forty-two participants were randomized and 40 completed the 6-month follow-up (n = 20 in both groups). No significant effects of mexiletine were observed on 6-minute walk distance, but hand grip myotonia was improved with mexiletine treatment. There were no differences between the mexiletine and placebo groups with respect to the frequency or type of adverse events. Changes in PR, QRS, and QTc intervals were similar in mexiletine- and placebo-treated participants. CONCLUSIONS: There was no benefit of mexiletine on 6-minute walk distance at 6 months. Although mexiletine had a sustained positive effect on objectively measured hand grip myotonia, this was not seen in measures reflecting participants' perceptions of their myotonia. No effects of mexiletine on cardiac conduction measures were seen over the 6-month follow-up period. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for ambulatory patients with DM1, mexiletine does not significantly change 6-minute walk distance at 6 months.
RCT Entities:
OBJECTIVE: To assess mexiletine's long-term safety and effect on 6-minute walk distance in a well-defined cohort of patients with myotonic dystrophy type 1 (DM1). METHODS: We performed a randomized, double-blind, placebo-controlled trial of mexiletine (150 mg 3 times daily) to evaluate its efficacy and safety in a homogenous cohort of adult ambulatory patients with DM1. The primary outcome was change in 6-minute walk distance at 6 months. Secondary outcomes included changes in hand grip myotonia, strength, swallowing, forced vital capacity, lean muscle mass, Myotonic Dystrophy Health Index scores, and 24-hour Holter and ECG results at 3 and 6 months. RESULTS: Forty-two participants were randomized and 40 completed the 6-month follow-up (n = 20 in both groups). No significant effects of mexiletine were observed on 6-minute walk distance, but hand grip myotonia was improved with mexiletine treatment. There were no differences between the mexiletine and placebo groups with respect to the frequency or type of adverse events. Changes in PR, QRS, and QTc intervals were similar in mexiletine- and placebo-treated participants. CONCLUSIONS: There was no benefit of mexiletine on 6-minute walk distance at 6 months. Although mexiletine had a sustained positive effect on objectively measured hand grip myotonia, this was not seen in measures reflecting participants' perceptions of their myotonia. No effects of mexiletine on cardiac conduction measures were seen over the 6-month follow-up period. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for ambulatory patients with DM1, mexiletine does not significantly change 6-minute walk distance at 6 months.
Authors: E L Logigian; W B Martens; R T Moxley; M P McDermott; N Dilek; A W Wiegner; A T Pearson; C A Barbieri; C L Annis; C A Thornton; R T Moxley Journal: Neurology Date: 2010-05-04 Impact factor: 9.910
Authors: Richard T Moxley; Eric L Logigian; William B Martens; Chris L Annis; Shree Pandya; Richard T Moxley; Cheryl A Barbieri; Nuran Dilek; Allen W Wiegner; Charles A Thornton Journal: Muscle Nerve Date: 2007-09 Impact factor: 3.217
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Authors: J D Brook; M E McCurrach; H G Harley; A J Buckler; D Church; H Aburatani; K Hunter; V P Stanton; J P Thirion; T Hudson Journal: Cell Date: 1992-02-21 Impact factor: 41.582
Authors: Tetsuo Ashizawa; Cynthia Gagnon; William J Groh; Laurie Gutmann; Nicholas E Johnson; Giovanni Meola; Richard Moxley; Shree Pandya; Mark T Rogers; Ericka Simpson; Nathalie Angeard; Guillaume Bassez; Kiera N Berggren; Deepak Bhakta; Marco Bozzali; Ann Broderick; Janice L B Byrne; Craig Campbell; Edith Cup; John W Day; Elisa De Mattia; Denis Duboc; Tina Duong; Katy Eichinger; Anne-Berit Ekstrom; Baziel van Engelen; Belen Esparis; Bruno Eymard; Marla Ferschl; Shahinaz M Gadalla; Benjamin Gallais; Todd Goodglick; Chad Heatwole; James Hilbert; Venessa Holland; Marie Kierkegaard; Wilma J Koopman; Kari Lane; Daphne Maas; Ami Mankodi; Katherine D Mathews; Darren G Monckton; David Moser; Saman Nazarian; Linda Nguyen; Peg Nopoulos; Richard Petty; Janel Phetteplace; Jack Puymirat; Subha Raman; Louis Richer; Elisabetta Roma; Jacinda Sampson; Valeria Sansone; Benedikt Schoser; Laurie Sterling; Jeffrey Statland; S H Subramony; Cuixia Tian; Careniña Trujillo; Gordon Tomaselli; Chris Turner; Shannon Venance; Aparajitha Verma; Molly White; Stefan Winblad Journal: Neurol Clin Pract Date: 2018-12
Authors: Andrew I Mikhail; Peter L Nagy; Katherine Manta; Nicholas Rouse; Alexander Manta; Sean Y Ng; Michael F Nagy; Paul Smith; Jian-Qiang Lu; Joshua P Nederveen; Vladimir Ljubicic; Mark A Tarnopolsky Journal: J Clin Invest Date: 2022-05-16 Impact factor: 19.456