Ph 2 Study of Triheptanoin for Tx of Long-Chain Fatty Acid Oxidation Disorder

描述（由申请人提供）： 脂肪酸氧化（FAO）障碍是一种罕见的遗传性疾病，影响估计1：9000婴儿。 最近在美国扩大的新生儿筛查小组中增加了脂肪酸氧化障碍，导致了这组疾病的早期诊断和治疗。 通过新生儿筛查进行的症状前治疗减少了代谢失调的发生，几乎消除了死亡率。 然而，患有长链脂肪酸氧化障碍的患者会经历长期并发症，例如伴有或不伴有心肌病的复发性横纹肌溶解症。 这一长链脂肪酸氧化亚组患者的患病率尚不清楚，但据估计，在美国约有1000人或更少。 这些疾病的新疗法已经落后于诊断能力。 研究人员建议测试一种新的治疗方法，假设增加柠檬酸循环中间体并最大限度地提高能量生产。 这项随机临床试验将检查三庚酸甘油酯补充剂（一种庚酸甘油三酯）治疗人类长链FAO疾病的疗效。 患有长链脂肪酸氧化障碍的受试者将被随机分配到两组中的一组：中链甘油三酯（MCT）补充剂、当前标准治疗或三庚酸甘油酯补充剂，持续4个月。 4个月后，研究将测试补充治疗对总能量消耗、对中等强度跑步机运动试验的反应、心脏功能和长链脂肪酸氧化能力的影响。 该项目的目标是确定三庚酸甘油酯治疗是否比常规治疗长链脂肪酸氧化障碍具有治疗优势。

DESCRIPTION (provided by applicant): Fatty acid oxidation (FAO) disorders are a family of rare inherited diseases affecting an estimated 1:9000 infants. The recent addition of the fatty acid oxidation disorders to the expanded newborn screening panel in the United States has led to the early diagnosis and treatment of this group of disorders. Presymptomatic treatment through newborn screening has decreased episodes of metabolic decompensation and nearly eliminated mortality. However, patients with a long-chain fatty acid oxidation disorders experience long-term complications such as recurrent rhabdomyolysis with or without cardiomyopathy. The prevalence of this sub-group of patients with long-chain fatty acid oxidation is unknown but it is estimated to affect approximately 1000 individuals or less in the United States. Novel treatments for these diseases have lagged behind the diagnostic capabilities. The investigators propose to test a novel treatment hypothesized to increase citric acid cycle intermediates and maximize energy production. This randomized clinical trial will examine the efficacy of triheptanoin supplementation (a heptanoate triglyceride) to treat humans with long-chain FAO disorders. Subjects with a long-chain fatty acid oxidation disorder will be randomly assigned to one of two groups: medium chain triglyceride (MCT) supplementation, the current standard of care, or triheptanoin supplementation for four months. After 4 months the study will test the effects of supplement treatment on total energy expenditure, the response to a moderate intensity treadmill exercise test, cardiac function and long-chain fatty acid oxidation capacity. The goal of the project is to determine if triheptanoin therapy has a therapeutic advantage over conventional treatment for long-chain fatty acid oxidation disorders.