Phase 2 Study of Orlistat and SLX-4090 for Type I Hyperlipoproteinemia

奥利司他和 SLX-4090 治疗 I 型高脂蛋白血症的 2 期研究

• 批准号: 8518255
• 负责人: Abhimanyu Garg
• 金额: $ 36.67万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2020-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8518255
• 关键词: Phase; Study; Orlistat; SLX; 4090

DESCRIPTION (provided by applicant): Type I hyperlipoproteinemia is a rare, autosomal recessive metabolic disorder characterized by extreme hypertriglyceridemia due to a deficiency in lipoprotein lipase or related proteins. Treatment of these patients is challenging as triglyceride-lowering medications are ineffective. A low fat diet is helpful, however, despite good dietary compliance, some patients continue to have severe hypertriglyceridemia and recurrent pancreatitis which can be life threatening. Therefore, this study will investigate whether inducing dietary fat malabsorption or inhibiting chylomicron formation will cause further lowering of serum TG beyond the effect of limiting dietary fat intake. The investigators will assess the efficacy and safety of an inhibitor of intestinal lipase (Orlistat) and an intestinal-specific inhibitor of microsomal triglyceride transport protein (MTP) involved in the assembly and secretion of chylomicrons (SLx-4090), alone and in combination, for reducing serum triglyceride levels in patients with type I hyperlipoproteinemia. This study will enroll 20 patients with type I hyperlipoproteinemia in a randomized, double-blind, placebo-controlled, cross-over trial. After a baseline evaluation, the subjects will be randomly assigned to placebo/placebo, Orlistat/placebo, SLx-4090/placebo or Orlistat/SLx-4090 for the duration of four weeks followed by a one week wash out period. During the last week of each study period, fasting blood samples will be drawn for three consecutive days for serum lipids and chemistry panel. The primary endpoint will be serum triglycerides; the secondary endpoint variables will be fasting and postprandial serum chylomicron-TG levels, postprandial serum TG levels during a meal tolerance test and retinyl palmitate levels during a meal tolerance test, and episodes of acute pancreatitis. Repeated measures analysis of variance will be used for statistical comparisons.

描述（由申请人提供）： I型高脂蛋白血症是一种罕见的常染色体隐性代谢疾病，其特征是由于脂蛋白脂肪酶或相关蛋白质缺乏，其特征是极端高甘油三酯血症。 这些患者的治疗是具有挑战性的，因为降解甘油三酸酯的药物无效。 低脂肪饮食有帮助，但是，尽管饮食良好，但一些患者继续患有严重的高甘油三酯血症和复发性胰腺炎，这可能会危及生命。因此，这项研究将研究诱导饮食脂肪吸收不良或抑制乳糜微粒形成是否会导致血清TG进一步降低，超出限制饮食脂肪摄入的影响。研究者将评估肠道脂肪酶（Orlistat）的抑制剂和肠道特异性抑制剂的微粒甘油三酸酯转运蛋白（MTP）涉及乳糜细节的组装和分泌，单独且组合型乳糜型（SLX-4090）（SLX-4090）的组合，用于trigine trigine i i rypyceria iCerligin i i clysiria I级别。 这项研究将在一项随机，双盲，安慰剂对照，交叉试验中招募20例I型高脂蛋白血症患者。 经过基线评估后，受试者将在四个星期的时间内随机分配给安慰剂/安慰剂，Orlistat/安慰剂，SLX-4090/安慰剂或Orlistat/Slx-4090，然后在一周的时间内洗了一周。 在每个研究期间的最后一周，将连续三天为血清脂质和化学面板绘制空腹血液样本。 主要终点是血清甘油三酸酯。次要终点变量将是禁食和餐后血清乳糜微粒-TG水平，餐后耐受性测试期间的餐后血清TG水平和餐食耐受性测试期间的视网膜棕榈酸酯水平以及急性胰腺炎发作。 重复测量方差分析将用于统计比较。