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

• 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
• 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

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）：常染色体显性多囊性肾脏疾病（ADPKD）是最常见的遗传肾脏疾病，是该国肾衰竭的第三大最常见原因。在ADPKD中，由于囊肿的发展和扩张，随着时间的推移，肾脏中的囊肿生长。早期的ADPKD患者患有高血压，这与更快的肾功能衰竭率有关。迄今为止，尚未针对疾病进展缓慢的高血压和ADPKD患者开发有效的疗法。重素贡环蛋白 - 醛固酮系统的激活与ADPKD中的高血压有关。现在有两类的降压药抑制了该系统的激活。这些包括血管紧张素转化酶抑制剂（ACEI）和血管紧张素受体阻断剂（ARB）。尚不清楚将这些药物组合在一起是否会有效地减慢ADPKD的肾衰竭进展，以及血压控制水平是否在减慢肾衰竭进展方面很重要。停顿是一项前瞻性纵向随机双盲研究，将在四年内的7个临床部位的1018名受试者中进行。埃默里大学将有254名涉及两个患者人群的学科。研究A将涉及受试者的年龄17-45岁，具有正常的肾功能（估计的GFR> 60 mL/min），并且将确定通过磁共振成像（MRI）测得的肾脏大小的变化率。受试者还将分为两个水平的血压控制水平，<110/75（严格控制）或<130/80 mm Hg（标准对照）。在研究组B中，受试者的年龄为18-64岁，其肾功能低于正常功能（估计的GFR 25-60 mL/min）将被治疗至相同水平的血压水平（<130/80 mM Hg）。研究B的综合主要终点包括时间增加血清肌酐浓度，肾脏替代疗法或死亡的时间。所有合格的受试者都将在其降压药中进行降压，进行基线评估，然后进行剂量滴定阶段和研究期间的维护阶段。这项研究将确定对RAA的双重抑制以及严格的血压控制在ADPKD中预防肾脏疾病进展的功效。