A randomized, controlled, double-blind, crossover trial of triheptanoin in alternating hemiplegia of childhood

Elodie Hainque, Samantha Caillet, Sandrine Leroy, Constance Flamand-Roze, Isaac Adanyeguh, Fanny Charbonnier-Beaupel, Maryvonne Retail, Benjamin Le Toullec, Mariana Atencio, Sophie Rivaud-Péchoux, Vanessa Brochard, Florence Habarou, Chris Ottolenghi, Florence Cormier, Aurélie Méneret, Marta Ruiz, Mohamed Doulazmi, Anne Roubergue, Jean Christophe Corvol, Marie VidailhetFanny Mochel, Emmanuel Roze

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Background: Based on the hypothesis of a brain energy deficit, we investigated the safety and efficacy of triheptanoin on paroxysmal episodes in patients with alternating hemiplegia of childhood due to ATP1A3 mutations. Methods: We conducted a randomized, double-blind, placebo-controlled crossover study of triheptanoin, at a target dose corresponding to 30% of daily calorie intake, in ten patients with alternating hemiplegia of childhood due to ATP1A3 mutations. Each treatment period consisted of a 12-week fixed-dose phase, separated by a 4-week washout period. The primary outcome was the total number of paroxysmal events. Secondary outcomes included the number of paroxysmal motor-epileptic events; a composite score taking into account the number, severity and duration of paroxysmal events; interictal neurological manifestations; the clinical global impression-improvement scale (CGI-I); and safety parameters. The paired non-parametric Wilcoxon test was used to analyze treatment effects. Results: In an intention-to-treat analysis, triheptanoin failed to reduce the total number of paroxysmal events (p = 0.646), including motor-epileptic events (p = 0.585), or the composite score (p = 0.059). CGI-I score did not differ between triheptanoin and placebo periods. Triheptanoin was well tolerated. Conclusions: Triheptanoin does not prevent paroxysmal events in Alternating hemiplegia of childhood. We show the feasibility of a randomized placebo-controlled trial in this setting. Trial registration: The study has been registered with clinicaltrials.gov (NCT002408354) the 03/24/2015.

Original languageEnglish (US)
Article number160
JournalOrphanet Journal of Rare Diseases
Volume12
Issue number1
DOIs
StatePublished - Oct 2 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 The Author(s).

Keywords

  • Alternating hemiplegia of childhood
  • Crossover trial
  • Triheptanoin

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