Physician Information for Clinical Trial on
"Improving Outcomes in Diabetic Nephropathy"

Diabetic nephropathy remains the number one cause of end-stage renal disease in the United States and around the world. There is no cure for diabetic nephropathy, but several factors have been shown to slow the progression. These include: 1) aggressive glycemic control of diabetes, 2) aggressive control of hypertension, and 3) use of ACE inhibitors (ACEi) in Type I diabetics and angiotensin receptor blockers (ARBs) in Type 2 diabetics, independent of blood pressure. While these strategies slow the progression, they do not prevent end stage renal disease.

Recently, the COOPERATE trial showed the combination of ACEi and ARB to offer superior protection than either agent alone in non-diabetics with chronic kidney disease. Currently, there are no studies that have determined the safety and efficacy of this combination in diabetics. Furthermore, recent evidence demonstrates that aldosterone may accelerate renal injury in chronic kidney disease. There are no studies that directly compare whether using a combination ACEi + ARB is superior to ACEi + mineralcorticoid antagonist (spironolactone) in reducing proteinuria in diabetic nephropathy. Furthermore, there is no evidence that either of these strategies is superior to high dose ACEi alone in diabetic nephropathy.

The clinical trial we have proposed will help answer these questions. All patients will receive 80 mg of lisinopril a day and be randomized to receive a study drug of losartan or spironolactone or placebo. All patients will receive aggressive treatment of their hypertension, with goal BP of <130/80, and be followed for one year in our research clinic (see Figure 1 below).

We are currently actively recruiting. If you have patients that meet the following criteria and are interested, please contact Margarita Dominguez, RN, Study Coordinator at phone: 214-648-7847 or Justin Teiwes, M.D., co-investigator at pager: 214-822-0769.

Inclusion Criteria
*Adult male and female subjects of all ethnic backgrounds, ages 20-60
*Type 1 or Type 2 diabetes mellitus
*Hypertension or SBP >130 mmHg
*Proteinuria defined as albumin/Cr ratio of >300 mg/g while on ACE inhibitor or ARB

Exclusion Criteria
*Serum Cr > 3.0 mg/dl in females and > 4.0 mg/dl in males
*Serum potassium >5.5 mEq/L on ACE inhibitor
*Stroke or myocardial infarction within preceding 12 months
*Ejection fraction <40%
*Pregnancy or attempting to become pregnant in next year
*Allergy to ACE inhibitor