Clinical trial of L‐Carnitine and valproic acid in spinal muscular atrophy type I. Issue 2 (18th September 2017)

• Record Type: Journal Article
• Authors: Krosschell, Kristin J.; Kissel, John T.; Townsend, Elise L.; Simeone, Sarah D.; Zhang, Ren Zhe; Reyna, Sandra P.; Crawford, Thomas O.; Schroth, Mary K.; Acsadi, Gyula; Kishnani, Priya S.; Von Kleist‐Retzow, Jürgen‐Christoph; Hero, Barbara; D'Anjou, Guy; Smith, Edward C.; Elsheikh, Bakri; Simard, Louise R.; Prior, Thomas W.; Scott, Charles B.; Lasalle, Bernard; Sakonju, Ai; Wirth, Brunhilde; Swoboda, Kathryn J.
• Is Part Of: Muscle & nerve. Volume 57:Issue 2(2018)
• Page Start: 193
• Page End: 199
• Publication Date: 2017-09-18
• Subjects: clinical trials -- infants -- natural history -- L‐carnitine -- spinal muscular atrophy type I -- valproic acid; Neuromuscular diseases -- Periodicals; Muscles -- Periodicals; Nerves -- Periodicals; 616.74
• DOI: 10.1002/mus.25776
• Languages: English
• ISSNs: 0148-639X

Abstract

ABSTRACT: Introduction: The aim of this study was to determine the safety and therapeutic potential ofL ‐carnitine and valproic acid (VPA) in infants with spinal muscular atrophy (SMA). Methods: Our investigation was an open‐label phase 2 multicenter trial ofL ‐carnitine and VPA in infants with SMA type I with retrospective comparison to an untreated, matched cohort. Primary outcomes were: safety and adverse events; secondary outcomes were survival, time to death/>16 hours/day of ventilator support; motor outcomes; and maximum ulnar compound motor action potential amplitude. Results: A total of 245 AEs were observed in 35 of the 37 treated subjects (95%). Respiratory events accounted for 49% of all adverse events, resulting in 14 deaths. Survival was not significantly different between treated and untreated cohorts. Discussion: This trial provides evidence that, in infants with SMA type I, L ‐carnitine/VPA is ineffective at altering survival. The substantial proportion of infants reaching end‐points within 6 months of enrollment underscores the urgent need for pre‐symptomatic treatment in SMA type I. Muscle Nerve 57 : 193–199, 2018