G. Gaslini Institute, Scientific Institute for Research and Health Care, Genoa, Italy.
Departments of Neurosciences, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health, University of Genoa, Genoa, Italy.
Epilepsia. 2022 Jul;63(7):1748-1760. doi: 10.1111/epi.17263. Epub 2022 May 21.
This study was undertaken to evaluate efficacy and long-term safety of triheptanoin in patients >1 year old, not on a ketogenic diet, with drug-resistant seizures associated with glucose transporter 1 deficiency syndrome (Glut1DS).
UX007G-CL201 was a randomized, double-blind, placebo-controlled trial. Following a 6-week baseline period, eligible patients were randomized 3:1 to triheptanoin or placebo. Dosing was titrated to 35% of total daily calories over 2 weeks. After an 8-week placebo-controlled period, all patients received open-label triheptanoin through Week 52.
The study included 36 patients (15 children, 13 adolescents, eight adults). A median 12.6% reduction in overall seizure frequency was observed in the triheptanoin arm relative to baseline, and a 13.5% difference was observed relative to placebo (p = .58). In patients with absence seizures only (n = 9), a median 62.2% reduction in seizure frequency was observed in the triheptanoin arm relative to baseline. Only one patient with absence seizures only was present in the control group, preventing comparison. No statistically significant differences in seizure frequency were observed. Common treatment-emergent adverse events included diarrhea, vomiting, abdominal pain, and nausea, mostly mild or moderate in severity. No serious adverse events were considered to be treatment related. One patient discontinued due to status epilepticus.
Triheptanoin did not significantly reduce seizure frequency in patients with Glut1DS not on the ketogenic diet. Treatment was associated with mild to moderate gastrointestinal treatment-related events; most resolved following dose reduction or interruption and/or medication for treatment. Triheptanoin was not associated with any long-term safety concerns when administered at dose levels up to 35% of total daily caloric intake for up to 1 year.
本研究旨在评估三庚酸甘油酯在 1 岁以上、未接受生酮饮食、伴葡萄糖转运蛋白 1 缺乏综合征（Glut1DS）相关耐药性癫痫发作的患者中的疗效和长期安全性。
UX007G-CL201 是一项随机、双盲、安慰剂对照试验。在 6 周的基线期后，符合条件的患者以 3:1 的比例随机分配至三庚酸甘油酯或安慰剂组。2 周内将剂量滴定至总日热量的 35%。在 8 周安慰剂对照期后，所有患者在第 52 周接受开放标签的三庚酸甘油酯治疗。
该研究纳入 36 例患者（15 例儿童、13 例青少年、8 例成人）。与基线相比，三庚酸甘油酯组的总癫痫发作频率中位数降低了 12.6%，与安慰剂相比降低了 13.5%（p=0.58）。在仅有失神发作的患者中（n=9），与基线相比，三庚酸甘油酯组的癫痫发作频率中位数降低了 62.2%。仅 1 例仅有失神发作的患者在对照组中，无法进行比较。未观察到癫痫发作频率的统计学显著差异。常见的治疗相关不良事件包括腹泻、呕吐、腹痛和恶心，大多为轻度或中度。无严重不良事件被认为与治疗相关。1 例患者因癫痫持续状态而停药。
对于未接受生酮饮食的 Glut1DS 患者，三庚酸甘油酯并不能显著降低癫痫发作频率。治疗与轻度至中度胃肠道相关治疗不良事件相关；大多数在减少剂量或中断治疗以及/或药物治疗后得到解决。在高达总日热量摄入的 35%的剂量水平下，连续 1 年给药时，三庚酸甘油酯未引起任何长期安全性问题。
