Mexiletine in Myotonic Dystrophy Type 1: A Randomized, Double-Blind, Placebo-Controlled Trial.
Journal
Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060
Informations de publication
Date de publication:
12 01 2021
12 01 2021
Historique:
received:
06
11
2019
accepted:
24
08
2020
pubmed:
14
10
2020
medline:
28
1
2021
entrez:
13
10
2020
Statut:
ppublish
Résumé
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). 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. 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. 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. This study provides Class I evidence that for ambulatory patients with DM1, mexiletine does not significantly change 6-minute walk distance at 6 months.
Identifiants
pubmed: 33046619
pii: WNL.0000000000011002
doi: 10.1212/WNL.0000000000011002
pmc: PMC7905778
doi:
Substances chimiques
Voltage-Gated Sodium Channel Blockers
0
Mexiletine
1U511HHV4Z
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, U.S. Gov't, P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e228-e240Subventions
Organisme : NINDS NIH HHS
ID : P50 NS048843
Pays : United States
Informations de copyright
© 2020 American Academy of Neurology.
Références
Muscle Nerve. 2007 Sep;36(3):320-8
pubmed: 17587223
Neurol Clin Pract. 2018 Dec;8(6):507-520
pubmed: 30588381
Acta Neurol Scand. 1992 Oct;86(4):371-5
pubmed: 1455983
Am J Respir Crit Care Med. 2002 Jul 1;166(1):111-7
pubmed: 12091180
Muscle Nerve. 2014 Jun;49(6):906-14
pubmed: 24142420
Cell. 1992 Feb 21;68(4):799-808
pubmed: 1310900
Neurology. 2007 Mar 27;68(13):1051-7
pubmed: 17389311
PLoS One. 2016 Feb 05;11(2):e0148264
pubmed: 26849574
Alcohol Alcohol. 2012 Sep-Oct;47(5):558-62
pubmed: 22753786
Neurology. 2010 May 4;74(18):1441-8
pubmed: 20439846
Science. 1992 Mar 6;255(5049):1256-8
pubmed: 1546326
JAMA. 2018 Dec 11;320(22):2344-2353
pubmed: 30535218
Scand J Gastroenterol. 2003 Sep;38(9):947-54
pubmed: 14531531
N Engl J Med. 2008 Jun 19;358(25):2688-97
pubmed: 18565861
Phys Ther. 1999 Apr;79(4):371-83
pubmed: 10201543
Arch Phys Med Rehabil. 1969 Jun;50(6):311-9
pubmed: 5788487
Eur J Gastroenterol Hepatol. 2005 Apr;17(4):411-20
pubmed: 15756093
Ann Intern Med. 1994 Aug 1;121(3):200-6
pubmed: 8017747
Muscle Nerve. 2013 Sep;48(3):357-68
pubmed: 23674289
Neurology. 2012 Jul 24;79(4):348-57
pubmed: 22786587
Neurology. 1997 Jan;48(1):38-46
pubmed: 9008491
JAMA. 2012 Oct 3;308(13):1357-65
pubmed: 23032552
Lancet. 1973 Aug 25;2(7826):399-404
pubmed: 4124889
Clin Biochem. 2010 Oct;43(15):1246-8
pubmed: 20691173
Med Care. 1992 Jun;30(6):473-83
pubmed: 1593914
Science. 1992 Mar 6;255(5049):1253-5
pubmed: 1546325
Br J Clin Pharmacol. 1998 Jul;46(1):55-62
pubmed: 9690950