Renin Angiotensin System Study (RASS/B-RASS) - Full Text View

Sponsor:	Michael Mauer, MD
Collaborators:	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Merck Merck Frosst Canada Ltd. Canadian Institutes of Health Research (CIHR)
Information provided by:	University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:	NCT00143949

Purpose

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

Study Type:	Interventional
Study Design:	Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	Renin Angiotensin System Blockage-DN (RASS)

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Diabetes Type 1 Diabetic Kidney Problems

Drug Information available for: Enalapril Enalapril maleate Enalaprilat Losartan

U.S. FDA Resources

Further study details as provided by University of Minnesota - Clinical and Translational Science Institute:

Primary Outcome Measures:

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

Secondary Outcome Measures:

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 ]

Enrollment:	285
Study Start Date:	March 1997
Study Completion Date:	May 2008
Primary Completion Date:	March 2007 (Final data collection date for primary outcome measure)

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

Eligibility

Ages Eligible for Study:	16 Years to 61 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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
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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00143949

Locations

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

Sponsors and Collaborators

Michael Mauer, MD

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Merck

Merck Frosst Canada Ltd.

Canadian Institutes of Health Research (CIHR)

Investigators

Principal Investigator:

S M Mauer, MD

University of Minnesota - Clinical and Translational Science Institute

More Information

Publications:

Mauer M, Zinman B, Gardiner R, Drummond KN, Suissa S, Donnelly SM, Strand TD, Kramer MS, Klein R, Sinaiko AR. ACE-I and ARBs in early diabetic nephropathy. J Renin Angiotensin Aldosterone Syst. 2002 Dec;3(4):262-9.

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

Mauer M, Zinman B, Gardiner R, Suissa S, Sinaiko A, Strand T, Drummond K, Donnelly S, Goodyer P, Gubler MC, Klein R. Renal and retinal effects of enalapril and losartan in type 1 diabetes. N Engl J Med. 2009 Jul 2;361(1):40-51.

Study ID Numbers:	9601M10705
Study First Received:	September 1, 2005
Last Updated:	November 5, 2008
ClinicalTrials.gov Identifier:	NCT00143949 History of Changes
Health Authority:	United States: Federal Government; United States: Food and Drug Administration

Keywords provided by University of Minnesota - Clinical and Translational Science Institute:

diabetes
nephropathy
kidney
retinopathy

Additional relevant MeSH terms:

Metabolic Diseases
Autoimmune Diseases
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Diabetes Mellitus
Endocrine System Diseases
Enzyme Inhibitors
Cardiovascular Agents

Antihypertensive Agents
Pharmacologic Actions
Protease Inhibitors
Enalapril
Diabetes Mellitus, Type 1
Therapeutic Uses
Angiotensin-Converting Enzyme Inhibitors
Glucose Metabolism Disorders

ClinicalTrials.gov processed this record on February 04, 2010