Renin Angiotensin System Study (RASS/B-RASS)

NCT00143949 | Completed Phase 2 DMC

• 1 other identifier: 9601M10705
• Study Type: interventional
• Target: 285
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Type 1 Diabetes

Keywords

diabetes; nephropathy; kidney; retinopathy

Outcome Measures

Primary Outcomes (2)

• 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

• To obtain two percutaneous renal biopsies from each patient, five years apart.

  5 year

Secondary Outcomes (1)

• 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

Interventions

enalapril DRUG

losartan DRUG

Eligibility Criteria

• Age: 16 Years - 61 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Michael Mauer, MD: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Merck Sharp & Dohme LLC: collaborator
• Merck Frosst Canada Ltd.: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (3)

Mt Sinai Hospital, University of Toronto (Clinical Ctr)

Toronto, Ontario, M5G 1X5, Canada

Location

Royal Victoria Hospital, McGill University (Data Center)

Montreal, Quebec, H3A 1A1, Canada

Location

Montreal Childrens Hospital, McGill University (Clinical Ctr)

Montreal, Quebec, H3H 1P3, Canada

Location

Related Publications (6)

• 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. doi: 10.3317/jraas.2002.048.

  PMID: 12584670 BACKGROUND

• Limonte CP, Prince DK, Hoofnagle AN, Galecki A, Hirsch IB, Tian F, Waikar SS, Looker HC, Nelson RG, Doria A, Mauer M, Kestenbaum BR, de Boer IH. Associations of Biomarkers of Tubular Injury and Inflammation with Biopsy Features in Type 1 Diabetes. Clin J Am Soc Nephrol. 2024 Jan 1;19(1):44-55. doi: 10.2215/CJN.0000000000000333. Epub 2023 Oct 23.

  PMID: 37871959 DERIVED

• Robiner WN, Strand TD, Mauer M; Renin Angiotensin System Study (RASS) Group. Adherence and renal biopsy feasibility in the Renin Angiotensin-System Study (RASS) primary prevention diabetes trial. Diabetes Res Clin Pract. 2013 Oct;102(1):25-34. doi: 10.1016/j.diabres.2013.06.004. Epub 2013 Sep 17.

  PMID: 24050942 DERIVED

• Harindhanavudhi T, Mauer M, Klein R, Zinman B, Sinaiko A, Caramori ML; Renin Angiotensin System Study (RASS) group. Benefits of Renin-Angiotensin blockade on retinopathy in type 1 diabetes vary with glycemic control. Diabetes Care. 2011 Aug;34(8):1838-42. doi: 10.2337/dc11-0476. Epub 2011 Jun 29.

  PMID: 21715517 DERIVED

• Klein R, Myers CE, Klein BE, Zinman B, Gardiner R, Suissa S, Sinaiko AR, Donnelly SM, Goodyer P, Strand T, Mauer M. Relationship of blood pressure to retinal vessel diameter in type 1 diabetes mellitus. Arch Ophthalmol. 2010 Feb;128(2):198-205. doi: 10.1001/archophthalmol.2009.391.

  PMID: 20142543 DERIVED

• 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. doi: 10.1056/NEJMoa0808400.

  PMID: 19571282 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus; Kidney Diseases; Retinal Diseases

Interventions

Enalapril; Losartan

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Study Officials

• S M Mauer, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: PARALLEL
• Sponsor Type: INDIV

Study Record Dates

• First Submitted: September 1, 2005
• First Posted: September 2, 2005
• Study Start: March 1, 1997
• Primary Completion: March 1, 2007
• Study Completion: May 1, 2008
• Last Updated: November 6, 2008

Record last verified: 2008-11

Locations

CA (3)