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Clinical trial of L‐Carnitine and valproic acid in spinal muscular atrophy type I
Author(s) -
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 KleistRetzow JürgenChristoph,
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.
Publication year - 2018
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.25776
Subject(s) - valproic acid , spinal muscular atrophy , medicine , sma* , adverse effect , carnitine , compound muscle action potential , clinical trial , retrospective cohort study , pediatrics , anesthesia , surgery , epilepsy , electrophysiology , mathematics , disease , combinatorics , psychiatry
The aim of this study was to determine the safety and therapeutic potential of L ‐carnitine and valproic acid (VPA) in infants with spinal muscular atrophy (SMA). Methods: Our investigation was an open‐label phase 2 multicenter trial of L ‐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