BackgroundParoxysmal movement disorders are common in Glut1 deficiency syndrome (Glut1DS). Not all patients respond to or tolerate ketogenic diets.ObjectivesThe objective was to evaluate the effectiveness and safety of triheptanoin in reducing the frequency of disabling movement disorders in patients with Glut1DS not receiving a ketogenic diet.MethodsUX007G‐CL301 was a randomized, double‐blind, placebo‐controlled, phase 3 crossover study. After a 6‐week run‐in, eligible patients were randomized 1:1 to the first sequence (triheptanoin/placebo or placebo/triheptanoin) titration plus maintenance, followed by washout and the opposite sequence titration plus maintenance. The placebo (safflower oil) matched the appearance, taste, and smell of triheptanoin. Open‐label triheptanoin was administered in the extension. The frequency of disabling paroxysmal movement disorder events per 4 weeks (recorded by diary during maintenance; primary endpoint) was assessed by Wilcoxon rank‐sum test.ResultsForty‐three patients (children, n = 16; adults, n = 27) were randomized and treated. There was no difference between triheptanoin and placebo in the mean (interquartile range) number of disabling paroxysmal movement disorder events (14.3 [4.7–38.3] vs. 11.8; [3.2–28.7]; Hodges‐Lehmann estimated median difference: 1.46; 95% confidence interval, −1.12 to 4.36; P = 0.2684). Treatment‐emergent adverse events were mild/moderate in severity and included diarrhea, vomiting, upper abdominal pain, headache, and nausea. Two patients discontinued the study because of non‐serious adverse events that were predominantly gastrointestinal. The study was closed early during the open‐label extension because of lack of effectiveness. Seven patients continued to receive triheptanoin compassionately.ConclusionThere were no significant differences between the triheptanoin and placebo groups in the frequency of disabling movement disorder events during the double‐blind maintenance period. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

中文翻译：

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与安慰剂相比，三庚酸在治疗 Glut1 缺乏综合征中的阵发性运动障碍方面没有显示出益处：随机 3 期研究的结果

背景阵发性运动障碍在 Glut1 缺乏综合征 (Glut1DS) 中很常见。并非所有患者都对生酮饮食有反应或耐受。目的目的是评估三庚酸甘油酯在降低未接受生酮饮食的 Glut1DS 患者致残性运动障碍频率方面的有效性和安全性。方法UX007G-CL301 是一项随机、双盲、安慰剂对照、3 期交叉研究。经过 6 周的磨合后，符合条件的患者按 1:1 的比例随机分配至第一个序列（三庚酸甘油酯/安慰剂或安慰剂/三庚酸甘油酯）滴定加维持，然后进行洗脱和相反序列滴定加维持。安慰剂（红花油）与三庚酸甘油酯的外观、味道和气味相匹配。在扩展中使用了开放标签的三庚酸甘油酯。通过 Wilcoxon 秩和检验评估每 4 周发生致残性阵发性运动障碍事件的频率（在维持期间通过日记记录；主要终点）。 结果 43 名患者（儿童，n = 16；成人，n = 27）被随机分组​​，治疗。三庚酸甘油酯和安慰剂在致残性阵发性运动障碍事件的平均（四分位数范围）数量上没有差异（14.3 [4.7-38.3] vs. 11.8；[3.2-28.7]；Hodges-Lehmann 估计中位差异：1.46；95%置信区间，-1.12 至 4.36；磷= 0.2684）。治疗中出现的不良事件的严重程度为轻度/中度，包括腹泻、呕吐、上腹痛、头痛和恶心。两名患者因主要是胃肠道的非严重不良事件而终止了研究。由于缺乏有效性，该研究在开放标签扩展期间提前结束。 7名患者继续同情地接受三庚酸甘油酯。结论三庚酸甘油酯组和安慰剂组在双盲维持期间致残性运动障碍事件的频率没有显着差异。 © 2024 作者。运动障碍由 Wiley periodicals LLC 代表国际帕金森和运动障碍协会出版。