University of Pittsburgh School of Medicine, UPMC Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA 15238, USA.
Department of Pediatrics School of Medicine, University of Utah, 30 N 1900 E, Salt Lake City, UT, USA.
Clin Nutr ESPEN. 2021 Feb;41:293-298. doi: 10.1016/j.clnesp.2020.11.018. Epub 2020 Dec 25.
BACKGROUND & AIMS: Long-chain fatty acid oxidation disorders (LC-FAOD) are rare, life-threatening, autosomal recessive disorders that lead to energy depletion and major clinical events (MCEs), such as acute metabolic crises of hypoglycemia, cardiomyopathy, and rhabdomyolysis. The aim of this study was to report a post hoc analysis of diet diary data from the phase 2 UX007-CL201 study (NCT01886378).
In the single-arm, open-label, phase 2 UX007-CL201 study, the safety and efficacy of 78 weeks of treatment with triheptanoin, an odd-carbon, medium-chain triglyceride consisting of three 7-carbon fatty acids on a glycerol backbone, was investigated in subjects with LC-FAOD versus a retrospective 78-week period when subjects were optimally managed under published dietary guidelines. Subject dietary reports were collected to analyze the relationship between diet, triheptanoin treatment, and MCEs. Referring metabolic physicians completed a survey on patient management and clinical outcomes before and after initiation of triheptanoin. Before initiating triheptanoin, subjects received a mean daily caloric intake (DCI) of 17.4% from medium-chain triglycerides (MCT). During the study, subjects received a mean of 27.5% DCI from triheptanoin. Protein (13.7% vs 14.5% DCI), long-chain fat (13.1% vs 10.5% DCI), and carbohydrate (55.3% vs 47.1% DCI) intake were consistent between the pre-triheptanoin and triheptanoin treatment periods, respectively.
Following 78 weeks of treatment, mean annualized MCE rate decreased by 48.1% (p = 0.021) and mean annualized MCE event-day rate decreased by 50.3% (p = 0.028). A weak association existed between improvement in annualized MCE rate and change in percent DCI from MCT (Spearman rank correlation: r = -0.38; 95% CI: -0.675, 0.016). However, there was large variability in the association and no specific pattern of change for larger or smaller changes in dose. Seventy-two percent of physicians reported that triheptanoin had a clinically meaningful benefit on medical management of their patients.
Treatment with triheptanoin at the protocol-specified dose decreased the rate of MCEs in patients with LC-FAOD independently from other dietary changes between the pre-triheptanoin and triheptanoin treatment periods.
ClinicalTrials.gov identifier: NCT01886378.
长链脂肪酸氧化障碍（LC-FAOD）是一种罕见的、危及生命的常染色体隐性遗传病，可导致能量耗竭和主要临床事件（MCEs），如低血糖急性代谢危象、心肌病和横纹肌溶解。本研究旨在报告 2 期 UX007-CL201 研究（NCT01886378）的饮食日记数据的事后分析。
在单臂、开放标签、2 期 UX007-CL201 研究中，对 78 周的三庚酸治疗进行了安全性和有效性评估，三庚酸是一种奇数碳、中链甘油三酯，由三个 7 碳脂肪酸组成在甘油骨架上，与 LC-FAOD 患者相比，在发表的饮食指南下最佳管理的 78 周回顾性期间进行了评估。收集受试者的饮食报告，以分析饮食、三庚酸治疗和 MCEs 之间的关系。参考代谢医生在开始三庚酸治疗前后完成了关于患者管理和临床结果的调查。在开始三庚酸治疗之前，受试者从中链甘油三酯（MCT）中获得平均每日热量摄入（DCI）的 17.4%。在研究期间，受试者从三庚酸中获得了平均 27.5% 的 DCI。在开始三庚酸治疗之前和治疗期间，蛋白质（13.7% vs 14.5% DCI）、长链脂肪（13.1% vs 10.5% DCI）和碳水化合物（55.3% vs 47.1% DCI）的摄入量保持一致。
治疗 78 周后，年化 MCE 发生率降低 48.1%（p=0.021），年化 MCE 事件日发生率降低 50.3%（p=0.028）。改善的年化 MCE 发生率与 MCT 百分比 DCI 的变化之间存在弱关联（Spearman 秩相关：r=-0.38；95%CI：-0.675，0.016）。然而，关联存在很大的可变性，并且剂量变化较大或较小，没有特定的变化模式。72%的医生报告说，三庚酸对他们患者的医疗管理有临床意义的益处。
按照方案规定的剂量使用三庚酸治疗可降低 LC-FAOD 患者 MCE 的发生率，与治疗前和治疗期间 MCT 之间的其他饮食变化无关。
ClinicalTrials.gov 标识符：NCT01886378。
