NCT00381134

Improving Outcomes in Patients With Kidney Disease Due to Diabetes

Improving Outcomes in Diabetic Nephropathy

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 92 (estimated)
• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) · NIH
• Sex: All
• Age: 21 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

Kidney disease affects about one out of three people with diabetes mellitus, a common medical problem. Treatment of kidney disease with medications that lower blood pressure can slow the kidney disease but there is no known cure. This study is designed to test the hypothesis that certain combination-based blood pressure lowering regimens (of FDA approved medications) are better than single agent-based regimens for lowering blood pressure and further slowing or preventing progression of this incurable disease

Detailed description

The long-range objective of this project is to prevent progression of diabetic nephropathy, the leading cause of end-stage renal disease (ESRD). In most patients diabetic nephropathy progresses inexorably to ESRD despite inhibition of the renin-angiotensin- aldosterone system with angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs). The specific aims of this proposal are to: 1) recruit a multiethnic cohort of 78 young adults (ages 20-40) with type 1 (n=36) or type 2 (n=36) diabetes and overt nephropathy (defined as a urine albumin/creatinine ratio \> 300 mg albumin/g creatinine) and randomize in a double blind fashion to a control group consisting of ACEI-based therapy alone (ramipril 40 mg once daily) or one of two experimental groups: a) ACEI + ARB (ramipril 40 mg once daily plus losartan 100 mg once daily) or b) ACEI + mineralocorticoid receptor antagonist (MRA) (ramipril 40 mg once daily plus spironolactone 25 mg once daily); 2) conduct a 12-month prospective study to determine if proteinuria is reduced to a greater extent when either the ARB or MRA is added to ACEi-based therapy. This study is powered to detect a 30% greater reduction in 24-hour urine albumin/creatinine ratio in either experimental group versus control (alpha = 0.05, beta=0.10, repeated measures analysis of variance). Secondary endpoints to be examined include: (a) serum potassium and creatinine to assess safety, (b) TGF-beta, as a surrogate marker for ongoing renal injury, (c) plasma renin activity, angiotensin II and aldosterone levels and (d) plasma lipids and lipoprotein composition; and 3) perform repeated ambulatory blood pressure monitoring (ABPM) to examine the renoprotective effect of the 3 different regimens at comparable 24-hour BP of \< 125/75 mmHg. The deliverables include: 1) documentation of the safety of maximal dose combination therapy; 2) the feasibility of utilizing 24-hr ABPM to establish BP independent renoprotective effects of specific antihypertensive therapies; and 3) provide preliminary data for future large-scale studies to test efficacy and safety of combining ACEi with MRA therapy on renal outcomes.

Conditions

• Diabetes
• Kidney Disease
• Hypertension

Interventions

Type	Name	Description
DRUG	losartan 100 mg orally once daily
DRUG	spironolactone 25 mg orally once daily
DRUG	placebo once orally once daily

Timeline

• Start date: 2003-07-01
• Completion: 2006-12-01
• First posted: 2006-09-27
• Last updated: 2010-03-02

Locations

1 site across 1 country: United States