Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Renin Angiotensin System Study (RASS/B-RASS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00143949
Recruitment Status : Completed
First Posted : September 2, 2005
Last Update Posted : November 6, 2008
Sponsor:
Collaborators:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Merck Sharp & Dohme Corp.
Merck Frosst Canada Ltd.
Canadian Institutes of Health Research (CIHR)
Information provided by:
University of Minnesota - Clinical and Translational Science Institute

Tracking Information
First Submitted Date  ICMJE September 1, 2005
First Posted Date  ICMJE September 2, 2005
Last Update Posted Date November 6, 2008
Study Start Date  ICMJE March 1997
Actual Primary Completion Date March 2007   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 8, 2007)
  • 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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 1, 2005)
  • 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.
Change History Complete list of historical versions of study NCT00143949 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 8, 2007)
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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 1, 2005)
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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Renin Angiotensin System Study (RASS/B-RASS)
Official Title  ICMJE Renin Angiotensin System Blockage-DN (RASS)
Brief 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

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Condition  ICMJE Type 1 Diabetes
Intervention  ICMJE
  • Drug: enalapril
  • Drug: losartan
Study Arms  ICMJE Not Provided
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 1, 2005)
285
Original Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE May 2008
Actual Primary Completion Date March 2007   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years to 61 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00143949
Other Study ID Numbers  ICMJE 9601M10705
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE Michael Mauer, MD
Collaborators  ICMJE
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  • Merck Sharp & Dohme Corp.
  • Merck Frosst Canada Ltd.
  • Canadian Institutes of Health Research (CIHR)
Investigators  ICMJE
Principal Investigator: S M Mauer, MD University of Minnesota - Clinical and Translational Science Institute
PRS Account University of Minnesota - Clinical and Translational Science Institute
Verification Date November 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP