Renin Angiotensin System Study (RASS/B-RASS)

Type 1 Diabetes Clinical Trial

Official title:

Renin Angiotensin System Blockage-DN (RASS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00143949
• Other study ID #: 9601M10705
• Status: Completed
• Phase: Phase 2
• First received: September 1, 2005
• Last updated: November 5, 2008
• Start date: March 1997
• Est. completion date: May 2008

Study information

• Verified date: November 2008
• Source: University of Minnesota - Clinical and Translational Science Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 285
• Est. completion date: May 2008
• Est. primary completion date: March 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 16 Years to 61 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• Type 1 Diabetes

Intervention

Drug:
• enalapril

• losartan

Locations

Country	Name	City	State
Canada	Montreal Childrens Hospital, McGill University (Clinical Ctr)	Montreal	Quebec
Canada	Royal Victoria Hospital, McGill University (Data Center)	Montreal	Quebec
Canada	Mt Sinai Hospital, University of Toronto (Clinical Ctr)	Toronto	Ontario

Sponsors (5)

Lead Sponsor	Collaborator
Michael Mauer, MD	Canadian Institutes of Health Research (CIHR), Merck Frosst Canada Ltd., Merck Sharp & Dohme Corp., National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

Canada, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		5 year
Primary	To obtain two percutaneous renal biopsies from each patient, five years apart.		5 year
Secondary	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