PILOT STUDY OF ATORVASTATIN IN CHILDREN WITH NEPHROSIS

描述（直接摘自申请人摘要） 现在有相当多的证据表明，慢性高脂血症是一种 在两个实验中进行性肾损伤显著危险因素 患有难治性肾病综合征（NS）的动物和人。的 在多大程度上可以通过处理 高脂血症与饮食和降脂药物的组合， 对NS耐药的儿童尚不清楚。本申请描述 一项试点研究，旨在评估研究这一问题的可行性， 一项大型多中心随机临床试验中的问题。主 我们的初步研究的目的是评估治疗的安全性和有效性 高脂血症（低密度脂蛋白胆固醇>160 mg/dl）的儿童与NS，其中 肾功能相对保存良好（GFR为正常值的230%），但在 在采取其他适当措施后仍有蛋白尿和高脂血症的患者 治疗他们的原发病已经筋疲力尽。待测的药物 是一种新的高效HMG-CoA还原酶抑制剂（阿托伐他汀）。的患者 参加这项研究的人将经历三个月的平衡期。期间 在此期间，我们将使患者接受低胆固醇饮食， 确保患者没有快速进展的肾病， 并消除任何降脂或其他排除药物的作用 在随机化之前。经过三个月的节食，病人会 分配至阿托伐他汀或安慰剂治疗组。的 然后对患者进行为期三个月的连续测量 比较治疗组的血脂谱、化学组和蛋白质排泄， 控制患者。在三个月的随机化期后，所有 患者将转换为阿托伐他汀再治疗6-9个月。 该研究将在15个临床中心进行， 招募和研究，并将由一个数据/行政协调 德克萨斯州达拉斯的协调中心。尽管这样做的主要目标 本研究旨在确定阿托伐他汀治疗高血压的安全性和有效性。 儿童抵抗NS和高脂血症，我们的研究还设计 为未来的潜在调查提供初步数据， 降低胆固醇水平可能对进展速度的影响 肾功能不全的患者。

DESCRIPTION (Taken directly from applicant's abstract) There is now considerable evidence that chronic hyperlipidemia is a significant risk factor for progressive renal injury in both experimental animals and humans with treatment-resistant nephrotic syndrome (NS). The extent to which this process can be interrupted by treating the hyperlipidemia with a combination of diet and a lipidlowering medication in children with resistant NS is not known. The present application describes a pilot study that is designed to assess the feasibility of studying this question in a large multicenter, randomized, clinical trial. The primary goal of our pilot study is to evaluate the safety and efficacy of treating hyperlipidemia (LDL cholesterol >160 mg/dl) in children with NS, in whom renal function is relatively well-preserved (GFR 230% of normal), but in whom proteinuria and hyperlipidemia persist after other appropriate measures to treat their primary disease have been exhausted. The agent to be tested is a new potent HMG-CoA reductase inhibitor (atorvastatin). Patients who enter this study will undergo a three month equilibration period. During this period, we will establish the patients on a low-cholesterol diet, ensure the patients do not have a rapidly progressive form of nephropathy, and wash out the effect of any lipid-lowering or other excluded drugs given to them before randomization. After three months of diet, the patients will be assigned to either treatment with atorvastatin or a placebo. The patients will then be followed for three months with serial measurements comparing lipid profiles, chemistry panels, and protein excretion in treated and control patients. Following the three month randomized period, all patients will be converted to atorvastatin for an additional 6-9 months. The study will be conducted in 15 clinical centers where patients will be recruited and studied, and will be coordinated by a Data/Administrative Coordinating Center in Dallas, Texas. Although the primary goal of this study is to determine the safety and efficacy of atorvastatin for treating children with resistant NS and hyperlipidemia, our studies are also designed to provide preliminary data for a future investigation into the potential effect that lowering cholesterol levels may have on the rate of progression of renal insufficiency in such patients.