Clinical Trial to Slow the Progression of ADPKD

减缓 ADPKD 进展的临床试验

• 批准号: 6643547
• 负责人: ROBERT W SCHRIER
• 金额: $ 49.12万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-15 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6643547
• 关键词: ACE inhibitors; amlodipine; angiotensin /renin /aldosterone hypertension; autosomal dominant trait; blood flow measurement; blood pressure; cardiovascular disorder; chronic renal failure; clinical research; clinical trials; combination chemotherapy; cooperative study; diuretics; drug screening /evaluation; furosemide; human subject; human therapy evaluation; irbesartan; kidney disorder chemotherapy; kidney function; kidney pharmacology; magnetic resonance imaging; patient oriented research; pharmacokinetics; polycystic kidney; renin angiotensin system

DESCRIPTION (provided by applicant): Autosomal dominant polycystic kidney disease (ADPKD) affects one in 500-1000 Americans and leads to end-stage renal disease (ESRD) in 50% of patients by age 60 years. Moreover, the life expectancy of ADPKD patients is significantly reduced compared with the general population, despite the availability of dialysis and transplantation, due to premature cardiovascular mortality. Recent advances have lead to greater understanding of the mechanisms of ADPKD, and several agents have been found to slow cyst growth in animal models. However, clinical interventions to ameliorate the course of ADPKD in humans are lacking. Therefore, the National Institute of Diabetes and Digestive and Kidney Diseases has proposed a PKD Clinical Trials Network to design and implement clinical trials to slow the progressive loss of renal function in PKD, including a large trial on blockade of the renin-angiotensin-aldosterone system (RAAS). The PKD Research Center at the University of Colorado Health Sciences Center maintains a database of nearly 800 families with ADPKD, and over 1000 family members have participated in previous clinical studies at our Center. Additional patients with ADPKD are available for recruitment from the Polycystic Kidney Research Foundation and from agreements with local health care providers. Thus, we are confident we can identify 500 patients with ADPKD who are eager and eligible to participate in a clinical trial. We propose both a large randomized controlled clinical trial featuring blockade of the RAAS and a pilot study to determine if treatment with an antiangiogenic agent slows the rate of renal growth in patients with ADPKD. Working in collaboration with the PKD Clinical Trials Network, our goal is to identify interventions that not only slow but prevent progression of ADPKD to ESRD, and interventions that ameliorate the cardiovascular complications in ADPKD. A 2 X 2 factorial design is proposed to examine the hypothesis that RAAS inhibition and rigorous blood pressure control will slow progression in advanced ADPKD and prevent progression of renal and cardiovascular disease in early ADPKD.

描述（由申请人提供）：常染色体显性多囊性肾脏疾病（ADPKD）影响了500-1000名美国人中的一人，并导致50％的患者到60岁时导致终末期肾脏疾病（ESRD）。此外，尽管透析和移植，但由于心血管过早，ADPKD患者的预期寿命显着降低，尽管透析和移植的寿命可显着降低。最近的进步已导致对ADPKD机制的更多了解，并且发现几种药物在动物模型中会减缓囊肿的生长。但是，缺乏减轻人类ADPKD进程的临床干预措施。因此，美国国家糖尿病与消化和肾脏疾病研究所提出了PKD临床试验网络，以设计和实施临床试验，以减慢PKD中肾功能的进行性丧失，包括对肾素 - 血管紧张素 - 甲词素系统封锁的大型试验（Raas）。科罗拉多大学健康科学中心的PKD研究中心保留了一个近800个患有ADPKD家庭的数据库，其中1000多名家庭成员参加了我们中心的临床研究。多囊肾脏研究基金会以及与当地医疗保健提供者的协议可从ADPKD患者招募。因此，我们有信心我们可以识别500名渴望参加临床试验的ADPKD患者。我们提出了一项大型随机对照临床试验，该试验具有阻断RAAS的封锁和试点研究，以确定用抗血管生成剂治疗是否会减慢ADPKD患者的肾脏生长速度。我们的目标是与PKD临床试验网络合作，我们的目标是确定干预措施不仅减慢，而且可以防止ADPKD发展为ESRD，并减轻ADPKD中心血管并发症的干预措施。提出了2 x 2阶乘设计，以研究以下假设：RAAS抑制和严格的血压控制将减缓晚期ADPKD的进展，并防止ADPKD早期肾脏和心血管疾病的进展。