Renin Angiotensin System Study (RASS/B-RASS)
Condition: Type 1 Diabetes
MeSH terms: Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 2

Summary: 
      To determine if renin angiotensin medications can prevent or delay the onset of diabetic
      kidney disease.
    

Detailed description: 
      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:

      Specific Aim To obtain baseline, 2.5 and 5 year retinal fundus photographs in the RASS
      patients.

      Hypothesis Cross-sectional and longitudinal relationships of retinal and renal structural
      abnormalities will emerge which will improve the predictive value of renal functional tests.
      Reduction of rennin-angiotensin system activity will prevent or retard the development of
      diabetic retinal lesions
    

Intervention name(s): enalapril; losartan
Intervention type(s): Drug; Drug
Intervention MeSH terms: Losartan; Enalapril
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Keywords: diabetes; nephropathy; kidney; retinopathy