Clinical trial of L-Carnitine and valproic acid in spinal muscular atrophy type I.

Abstract

INTRODUCTION:

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.

• Authors: Kristin J Krosschell, John T Kissel, Elise L Townsend, Sarah D Simeone, Ren Zhe Zhang, Sandra P Reyna, Thomas O Crawford, Mary K Schroth, Gyula Acsadi, Priya S Kishnani, Jürgen-Christoph Von Kleist-Retzow, Barbara Hero, Guy D'Anjou, Edward C Smith, Bakri Elsheikh, Louise R Simard, Thomas W Prior, Charles B Scott, Bernard Lasalle, Ai Sakonju, Brunhilde Wirth, Kathryn J Swoboda, Project Cure SMA Investigator's Network
• Journal: Muscle & nerve (Muscle Nerve) Vol. 57 Issue 2 Pg. 193-199 (02 2018) ISSN: 1097-4598 [Electronic] United States
• PMID: 28833236 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 Wiley Periodicals, Inc.

Chemical References

• GABA Agents
• Vitamin B Complex
• Valproic Acid
• Carnitine

Topics

• Action Potentials (drug effects)
• Carnitine (adverse effects, therapeutic use)
• Cohort Studies
• Drug Therapy, Combination
• Female
• GABA Agents (adverse effects, therapeutic use)
• Humans
• Infant
• Male
• Negative Results
• Respiration, Artificial
• Retrospective Studies
• Spinal Muscular Atrophies of Childhood (drug therapy, physiopathology)
• Survival Analysis
• Treatment Outcome
• Valproic Acid (adverse effects, therapeutic use)
• Vitamin B Complex (adverse effects, therapeutic use)