Université de la Sorbonne, UPMC Paris 06, UMR S 1127, Inserm U 1127, CNRS UMR 7225, Institut du Cerveau et de la Moëlle, F-75013, Paris, France.
Département de Neurologie, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, 75013, Paris, France.
Orphanet J Rare Dis. 2017 Oct 2;12(1):160. doi: 10.1186/s13023-017-0713-2.
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.
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.
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.
Triheptanoin does not prevent paroxysmal events in Alternating hemiplegia of childhood. We show the feasibility of a randomized placebo-controlled trial in this setting.
The study has been registered with clinicaltrials.gov ( NCT002408354 ) the 03/24/2015.
基于脑能量不足的假说，我们研究了三庚酸甘油酯在 ATP1A3 突变所致儿童交替性偏瘫阵发性发作患者中的安全性和疗效。
我们对 10 例因 ATP1A3 突变所致儿童交替性偏瘫的患者进行了三庚酸甘油酯的随机、双盲、安慰剂对照交叉研究。三庚酸甘油酯的目标剂量相当于每日热量摄入的 30%，每个治疗期包括 12 周的固定剂量期，间隔 4 周洗脱期。主要结局是阵发性事件的总数。次要结局包括阵发性运动性癫痫发作的次数；综合评分，考虑阵发性事件的次数、严重程度和持续时间；发作间期神经表现；临床总体印象改善量表（CGI-I）；以及安全性参数。采用配对非参数 Wilcoxon 检验分析治疗效果。
在意向治疗分析中，三庚酸甘油酯未能减少阵发性事件的总数（p=0.646），包括运动性癫痫发作（p=0.585）或综合评分（p=0.059）。CGI-I 评分在三庚酸甘油酯和安慰剂期间无差异。三庚酸甘油酯耐受性良好。
三庚酸甘油酯不能预防儿童交替性偏瘫的阵发性事件。我们在这种情况下证明了随机安慰剂对照试验的可行性。
该研究已在 clinicaltrials.gov 上注册（NCT002408354），注册日期为 2015 年 3 月 24 日。
