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

Elodie HainqueEmail author,
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 Vidailhet,
Fanny Mochel† and
Emmanuel Roze†

†Contributed equally

Orphanet Journal of Rare Diseases201712:160

https://doi.org/10.1186/s13023-017-0713-2

Received: 6 April 2017

Accepted: 25 September 2017

Published: 2 October 2017

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.