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

Condition	Intervention	Phase
Type 1 Diabetes	Drug: enalapril  Drug: losartan	Phase II

Further Study Details: 

Primary Outcomes: 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.; To obtain two percutaneous renal biopsies from each patient, five years apart.
Secondary Outcomes: 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.
Expected Total Enrollment:  285

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-angiontensin 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

Ages Eligible for Study:  16 Years   -   61 Years,  Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

Inclusion Criteria:

• 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
• normalalbuminuric (<20 ug/min on 2 of 3 time overnight urine collections)

Exclusion Criteria:

• 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 systic 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)

Canada, Ontario
      Mt Sinai Hospital, University of Toronto (Clinical Ctr), Toronto,  Ontario,  M5G 1X5,  Canada
Canada, Quebec
      Montreal Childrens Hospital, McGill University (Clinical Ctr), Montreal,  Quebec,  H3H 1P3,  Canada
      Royal Victoria Hospital, McGill University (Data Center), Montreal,  Quebec,  H3A 1A1,  Canada

Study chairs or principal investigators

S M Mauer, MD,  Principal Investigator,  University of Minnesota   

Study ID Numbers:  9601M10705
Last Updated:  September 1, 2005
Record first received:  September 1, 2005
ClinicalTrials.gov Identifier:  NCT00143949
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-09-13