Limited Competition: Clinical Centers for the HALT-Polycystic Kidney Disease Tria

有限竞争：HALT-多囊肾病三项临床中心

基本信息

批准号：
7920518
负责人：
ARLENE B CHAPMAN
金额：
$ 11.01万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-21 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7920518
关键词：
Adverse effects Age Albuminuria Aldosterone Angiotensin Receptor Angiotensin-Converting Enzyme Inhibitors Antihypertensive Agents Autosomal Dominant Polycystic Kidney Blood Pressure Cardiovascular system Cessation of life Clinical Combined Modality Therapy Country Creatinine Cyst Development Disease Progression Dose Double-Blind Method End stage renal failure Evaluation Excretory function Frequencies Genetic Hospitalization Hypertension Individual Kidney Kidney Diseases Kidney Failure Left Ventricular Mass Magnetic Resonance Imaging Maintenance Measures Medical Pain Patients Pharmaceutical Preparations Phase Polycystic Kidney Diseases Principal Investigator Quality of life Questionnaires Randomized Renal Blood Flow Renal Replacement Therapy Renal function Serum Study Subject Symptoms System Time Titrations Universities blood pressure regulation clinical research site effective therapy patient population prevent prospective urinary

项目摘要

DESCRIPTION (provided by applicant): Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common genetic renal disease and is the third most common cause of renal failure in this country. In ADPKD cysts grow in the kidneys over time due to cyst development and expansion. Early ADPKD patients develop hypertension which is associated with a faster rate of progression to renal failure. To date no effective therapy has been developed for patients with hypertension and ADPKD that slow progression of disease. Activation of the reninangeotensin- aldosterone system is associated with hypertension in ADPKD. There are now two classes of antihypertensive medications which inhibit the activation of this system. These include Angiotensin Converting Enzyme Inhibitors (ACEI) and Angiotensin Receptor Blocking Agents (ARB). It is not known whether combining these agents together will be effective in slowing progression of renal failure in ADPKD and if levels of blood pressure control are important in slowing progression of renal failure. HALT is a prospective longitudinal randomized double blinded study will be performed in 1018 subjects at 7 clinical sites over a period of four years. There will be 254 subjects studied at Emory University involving two patient populations. Study A will involve subjects' age 17-45 years with normal renal function (estimated GFR > 60 ml/min) and the rate of change in renal size measured by magnetic resonance imaging (MRI) will be determined. Subjects will also be separated into two levels of blood pressure control, <110/75 (rigorous control) or <130/80 mm Hg (standard control). In study Group B, subjects' age 18-64 years with less than normal renal function (estimated GFR 25-60 ml/min) will be treated to the same level of blood pressure level (<130/80 mm Hg). The composite primary end point for Study B includes time to doubling of serum creatinine concentration, renal replacement therapy or death. All eligible subjects will undergo washout from their antihypertensive medications, undergo a baseline evaluation, followed by a dose titration phase and a maintenance phase for the duration of the study. This study will determine the efficacy of dual inhibition of the RAAS as well as rigorous blood pressure control in preventing progression of renal disease in ADPKD.

描述（由申请人提供）：常染色体显性多囊肾病（ADPKD）是最常见的遗传性肾病，也是该国肾衰竭的第三大常见原因。在 ADPKD 中，由于囊肿的发育和扩张，囊肿会随着时间在肾脏中生长。早期 ADPKD 患者会出现高血压，这与肾衰竭进展速度加快有关。迄今为止，尚未开发出针对高血压和 ADPKD 患者减缓疾病进展的有效疗法。肾素紧张素-醛固酮系统的激活与 ADPKD 中的高血压相关。现在有两类抗高血压药物可以抑制该系统的激活。这些包括血管紧张素转换酶抑制剂（ACEI）和血管紧张素受体阻断剂（ARB）。目前尚不清楚将这些药物联合起来是否能有效减缓 ADPKD 肾衰竭的进展，以及血压控制水平是否对减缓肾衰竭的进展很重要。 HALT 是一项前瞻性纵向随机双盲研究，将在四年内对 7 个临床中心的 1018 名受试者进行研究。埃默里大学将研究涉及两个患者群体的 254 项受试者。研究 A 将涉及年龄为 17-45 岁、肾功能正常（估计 GFR > 60 ml/min）的受试者，并将确定通过磁共振成像 (MRI) 测量的肾脏大小的变化率。受试者还将被分为两个血压控制水平：<110/75（严格控制）或<130/80 mm Hg（标准控制）。在研究 B 组中，年龄为 18-64 岁、肾功能低于正常（估计 GFR 25-60 ml/min）的受试者将接受相同水平的血压水平（<130/80 mm Hg）治疗。研究 B 的复合主要终点包括血清肌酐浓度加倍的时间、肾脏替代治疗或死亡。所有符合条件的受试者都将接受抗高血压药物的清除，接受基线评估，然后是研究期间的剂量滴定阶段和维持阶段。这项研究将确定 RAAS 双重抑制以及严格血压控制在预防 ADPKD 肾脏疾病进展方面的功效。