Renin Angiotensin System Blockage-DN (RASS)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 285
- 试验地点
- 6
- 主要终点
- To recruit 285 type 1 DM Pts without HTN, diabetic nephropathy, or microalbuminuria into a 5-year study to determine the effect of inhibition RAS with either losartan or enalapril.
研究概览
简要总结
To determine if renin angiotensin medications can prevent or delay the onset of diabetic kidney disease.
详细描述
The primary objective of this research is to determine, in type 1 (insulin-dependent) diabetic patients without hypertension, diabetic nephropathy (DN), or levels of microalbuminuria (MA) predictive of underlying, already established serious lesion of diabetic nephropathy, if inhibition of renin-angiotensin system (RAS) activity can prevent or retard the rate of development of the histologic lesions associated with DN. This primary prevention study is designed to examine the effect of pharmacologic intervention on the earliest stages of diabetic kidney disease. At the stage of overt DN intervention studies have shown only a slowing, as opposed to arrest, in disease progression, and benefit a minority of treated patients. At the MA stage the renal lesions of DN are already usually firmly established; moreover, progression in MA patients may occur despite strict glycemic or anti-hypertensive control. Renal histologic change over time has been selected as the primary endpoint in order to study the early stages of this disease, since the time to functional endpoints from these earlier stages precludes practical study design.
Specific Aim 1 To recruit 285 type 1 diabetic patients who do not have hypertension, diabetic nephropathy, or predictive levels of microalbuminuria into a 5-year study to determine the effect of inhibition of renin-angiotensin system activity with either losartan (angiotensin II blocker) or enalapril (converting enzyme inhibitor) on the development of diabetic renal disease. This aim has been accomplished and the study is entitled the Renin-Angiotension System Study (RASS).
Specific Aim 2 To obtain two percutaneous renal biopsies from each patient, the first, at entry into the study, and the second after five years of drug therapy with either losartan or enalapril.
Hypothesis Reduction of renin-angiotensin system activity will prevent or retard the development of histologic change in the kidney associated with diabetic nephropathy.
A secondary objective of this study is to evaluate retinal lesions in the RASS cohort of patients in order to determine the relationship of these findings to the histologic changes of DN and to examine the effects of RAS inhibition and/or systemic blood pressure (BP) on the development and progression of diabetic retinopathy. This ancillary study has the following aims:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 16 Years 至 61 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •type 1 diabetic (DM) for 2-20 yrs
- •type 1 DM onset prior to 45; if onset was between ages 31-41, BMI <26; onset 41-45, positive GAD or ICA required
- •normal or increased GFR
- •normal BP
- •normoalbuminuric (<20 ug/min on 2 of 3 time overnight urine collections)
排除标准
- •type 1 DM duration longer than 20 yrs
- •hypertension (>85/135 mmHg)
- •reduced GFR (<90 ml/min/1.73m2)
- •microalbuminuria
- •solitary kidney or evidence of unilateral renal disease
- •evidence of other important kidney disease by history, ultrasound or biopsy
- •other chronic diseases or conditions such as cystic fibrosis, serious mental illness, severe mental retardation, etc.
- •pregnancy or females planning pregnancy within 2 years were excluded due to the drugs being used
- •compliance (pt not taking at least 85% of two week placebo were excluded)
结局指标
主要结局
To recruit 285 type 1 DM Pts without HTN, diabetic nephropathy, or microalbuminuria into a 5-year study to determine the effect of inhibition RAS with either losartan or enalapril.
时间窗: 5 year
To obtain two percutaneous renal biopsies from each patient, five years apart.
时间窗: 5 year
次要结局
- To evaluate retinal lesions in RASS cohort to determine relationship to the histologic changes of DN and the effects of RAS inhibition and/or systemic blood pressure.(5 year)