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

描述(申请人提供)：常染色体显性遗传性多囊肾病(ADPKD)是最常见的遗传性肾脏疾病，是导致我国肾功能衰竭的第三大常见原因。在ADPKD中，由于囊肿的发展和扩大，随着时间的推移，囊肿在肾脏中生长。早期ADPKD患者发生高血压，与进展为肾功能衰竭的速度更快有关。到目前为止，还没有为高血压和ADPKD患者开发出有效的治疗方法来减缓疾病的进展。肾素-醛固酮系统的激活与ADPKD的高血压有关。现在有两类抗高血压药物可以抑制这一系统的激活。这些药物包括血管紧张素转换酶抑制剂(ACEI)和血管紧张素受体阻滞剂(ARB)。目前尚不清楚联合应用这些药物是否能有效延缓ADPKD患者肾功能衰竭的进展，以及血压控制水平是否对延缓肾功能衰竭的进展起着重要作用。HALT是一项前瞻性、纵向、随机、双盲研究，将在7个临床地点的1018名受试者中进行，为期四年。将有254名受试者在埃默里大学进行研究，涉及两个患者群体。研究A将涉及17-45岁肾功能正常的受试者(估计GFR和GT；60毫升/分钟)，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，&lt；110/75(严格控制)或&lt；130/80毫米汞柱(标准对照)。在研究B组，18-年龄的受试者肾功能低于正常(估计肾小球滤过率为25-60毫升/分钟)，将接受相同水平的血压治疗(&lt；130/80毫米汞柱)。研究B的综合主要终点包括血肌酐浓度增加一倍的时间、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淘汰，接受基线评估，然后是剂量滴定阶段和研究期间的维持阶段。这项研究将确定双重抑制RAAS和严格控制血压在预防ADPKD肾脏疾病进展方面的有效性。

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.