PILOT STUDY OF ATORVASTATIN IN CHILDREN WITH NEPHROSIS

描述(直接取自申请人的摘要) 现在有相当多的证据表明慢性高脂血症是一种 进展性肾损伤的显著危险因素 患有难治性肾病综合征(NS)的动物和人类。这个 可以在多大程度上中断此进程 饮食与降脂药物联合治疗高脂血症 患有耐药NS的儿童尚不清楚。本申请描述了 一项旨在评估研究这一问题的可行性的试验性研究 在一项大型多中心随机临床试验中提出问题。初级阶段 我们的初步研究的目标是评估治疗的安全性和有效性。 肾病综合征儿童的高脂血症(低密度脂蛋白和160 mg/dl)，其中 肾功能相对保存良好(GFR是正常的230%)，但在 在采取其他适当措施后，谁的蛋白尿和高脂血症仍然存在 治疗他们的原发病已经筋疲力尽了。被测试的试剂 是一种新型高效的HMG-CoA还原酶抑制剂(阿托伐他汀)。患者 进入这项研究将经历三个月的平衡期。在.期间 在此期间，我们将建立患者的低胆固醇饮食， 确保患者不会出现快速进展的肾病， 并消除任何降脂药物或其他排除药物的影响 在随机化之前给他们。在三个月的饮食后，患者将 被分配到阿托伐他汀或安慰剂治疗。这个 然后对患者进行为期三个月的连续测量。 比较治疗后的血脂、化学成分和蛋白质排泄量 并控制病人。在三个月的随机期之后，所有 患者将再服用阿托伐他汀6-9个月。 这项研究将在15个临床中心进行，患者将在 招聘和研究，并将由数据/行政协调 位于德克萨斯州达拉斯的协调中心。尽管这一行动的主要目标是 研究确定阿托伐他汀治疗的安全性和有效性 对于患有耐药NS和高脂血症的儿童，我们的研究也是 为未来的潜在调查提供初步数据 降低胆固醇水平可能会对进展速度产生影响 这类患者的肾功能不全。

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.