Improving Outcomes in Diabetic Nephropathy

改善糖尿病肾病的治疗效果

• 批准号: 6951024
• 负责人: ROBERT Daniel TOTO
• 金额: $ 41万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6951024
• 关键词: ACE inhibitors; aldosterone; antihypertensive agents; blood chemistry; blood pressure; clinical research; clinical trials; combination chemotherapy; diabetes mellitus; diabetic nephropathy; diuretics; drug adverse effect; human subject; human therapy evaluation; kidney disorder chemotherapy; longitudinal human study; losartan; outcomes research; patient oriented research; proteinuria; renal hypertension; spironolactone; urinalysis

DESCRIPTION (provided by applicant): The purpose of this R01 competitive renewal (response to NIDDK RFA 0025) is to request funds to complete recruitment, randomization and data analysis of a pilot study designed to determine the safety and efficacy (proteinuria) of combining an angiotensin converting enzyme inhibitor (ACEi) with either an angiotensin type 1 receptor blocker (ARB) or a mineralocorticoid antagonist (MRA) as compared to an ACE inhibitor alone in diabetics with nephropathy. This study is a randomized, double-blind placebo-controlled trial in a multiethnic cohort of type 1 and type 2 diabetics with persistent urine albumin/ creatinine ratio >= 300 mg/g despite maximally-dosed ACEi (lisinopril 80 mg per day or ramipril 40 mg per day). Study subjects are randomized into one of three groups to receive add-on treatment with placebo or spironolactone (25 mg/day) or losartan (100 mg/day) for 48 weeks with similar blood pressure control (< 130/< 80 mmHg). Ambulatory blood pressure monitoring is performed at baseline and periodically throughout the study. In the past 15 months we successfully built our study team, database and recruitment strategy. We screened more than 2500 potential participants, conducted 37 screening visits and successfully randomized 12 patients including 2 white, 6 black and 4 Hispanics among whom 40% are type 1 and 60% are type 2 diabetics between the ages of 20-60. To date, there have been no drop outs. We plan to complete recruitment and randomization of about 90 participants, of whom 78 are expected to complete the study (15% drop our rate). This will provide 90% power to detect a 30% decrease in urinary albumin/creatinine ratio in either experimental group as compared to the placebo group (o=0.05, ANOVA). Recruitment has accelerated dramatically in the past 3 months. We expect to complete recruitment by the end of the first year and follow-up by the end of the second year of funding. We anticipate this study will: 1) establish the safety and effectiveness of maximal dose combination therapy; 2) determine feasibility of extensively utilizing 24-hour ABPM in future large-scale trials designed to establish BP independent renoprotective effects of specific antihypertensives; and 3) provide preliminary data for a future large-scale study to test the efficacy and safety of combining ACEi therapy with an ARB or a MRA on renal outcomes in diabetics.

描述（由申请人提供）： The purpose of this R01 competitive renewal (response to NIDDK RFA 0025) is to request funds to complete recruitment, randomization and data analysis of a pilot study designed to determine the safety and efficacy (proteinuria) of combining an angiotensin converting enzyme inhibitor (ACEi) with either an angiotensin type 1 receptor blocker (ARB) or a mineralocorticoid antagonist (MRA)与仅在患有肾病的糖尿病患者中与ACE抑制剂相比。这项研究是一项随机，双盲安慰剂对照试验，在1型和2型糖尿病患者中，具有持续的尿白蛋白/肌酐比> = 300 mg/ g的糖尿病患者，尽管最大毒气（尽管每天lisinopril每天80 mg或ramipril 40 mg每天）。研究对象被随机分为三组之一，以接受安慰剂或螺内酯（25 mg/day）或Losartan（100 mg/day）的插件治疗，持续48周（<130/<80 mmHg）。在整个研究中，在基线和定期进行卧床血压监测。在过去的15个月中，我们成功建立了我们的研究团队，数据库和招聘策略。我们筛选了2500多名潜在参与者，进行了3​​7次筛查访问，并成功地随机分组了12例患者，包括2名白色，6种黑人和4种西班牙裔，其中40％为1型和60％是20-60岁之间的2型糖尿病患者。迄今为止，还没有掉落。我们计划完成约90名参与者的招聘和随机分组，其中78名参与者将完成这项研究（15％降低了我们的比率）。与安慰剂组相比，这将提供90％的功率，以检测两个实验组尿白蛋白/肌酐比率的30％（O = 0.05，ANOVA）。在过去的三个月中，招聘急剧加速。我们预计将在第一年结束前完成招聘，并在资金第二年结束之前进行随访。我们预计这项研究将：1）确定最大剂量组合疗法的安全性和有效性； 2）确定在未来的大规模试验中广泛利用24小时ABPM的可行性，该试验旨在建立特定的抗高血压剂的BP独立肾脏保护作用； 3）提供初步数据，用于未来的大规模研究，以测试将ACEI治疗与ARB或MRA合并糖尿病患者肾脏结局的功效和安全性。