Renin Angiotensin System Study (RASS/B-RASS)

November 5, 2008 updated by: Michael Mauer, MD

Renin Angiotensin System Blockage-DN (RASS)

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

285

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 61 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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
  • normoalbuminuric (<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 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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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.
Time Frame: 5 year
5 year
To obtain two percutaneous renal biopsies from each patient, five years apart.
Time Frame: 5 year
5 year

Secondary Outcome Measures

Outcome Measure
Time Frame
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.
Time Frame: 5 year
5 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Michael Mauer, MD

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Merck Sharp & Dohme LLC
Canadian Institutes of Health Research (CIHR)
Merck Frosst Canada Ltd.

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 1997

Primary Completion (Actual)

March 1, 2007

Study Completion (Actual)

May 1, 2008

Study Registration Dates

First Submitted

September 1, 2005

First Submitted That Met QC Criteria

September 1, 2005

First Posted (Estimate)

September 2, 2005

Study Record Updates

Last Update Posted (Estimate)

November 6, 2008

Last Update Submitted That Met QC Criteria

November 5, 2008

Last Verified

November 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 9601M10705

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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