Improving Outcomes in Patients With Kidney Disease Due to Diabetes
Condition: Diabetes; Kidney Disease; Hypertension
MeSH terms: Kidney Diseases
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): losartan 100 mg orally once daily; spironolactone 25 mg orally once daily; placebo once orally once daily
Intervention type(s): Drug; Drug; Drug
Intervention MeSH terms: Losartan; Spironolactone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: double-blind; placebo-controlled; nephropathy; blood pressure; urine albumin to creatinine ratio; placebo