Improving Outcomes in Patients With Kidney Disease Due to Diabetes

• Status: Completed
• Trial end date: 2006-12-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Treatments: Losartan; Spironolactone

Criteria

Inclusion Criteria:

• Adult male and female subjects aged 20-65 of all ethnic backgrounds.

• Type I diabetes mellitus defined as sudden onset of insulin requiring diabetes prior to age 20 and at least 5 years duration

• Type 2 diabetes mellitus defined as onset > 20 years of age and treatment with oral hypoglycemic agent and/or insulin and increased C-peptide level.

• Seated SBP > 130 mmHg documented at one screening visit or treated SBP < 130 mmHg with a documented history of SBP > 130 mmHg on more than one previous occasion

• Proteinuria defined as a 24-hour urine albumin/creatinine ratio > 300 mg/g while on an ACE inhibitor with or without non-ARB, non-aldosterone antagonist treatment

• Ongoing treatment (> 3 months) with an ACE inhibitor or ARB with or without additional antihypertensive therapy (e.g. CCB, a-blocker, b-blocker, clonidine).

Exclusion Criteria:

• BMI > 45 kg/m2

• Baseline serum creatinine > 3.0 mg/dl in females and > 4.0 mg/dl in males or creatinine clearance <20 ml/min estimated by Cockcroft-Gault equation (based on age, fasting serum creatinine concentration and ideal body weight in kilograms).

• Secondary cause of kidney disease other than diabetic nephropathy

• Serum potassium concentration >5.5 mEq/L on ACE inhibitor therapy 7-10 days prior to randomization

• Poorly controlled diabetes, i.e. HgbA1C > 11 mg/dl 7-10 days prior to randomization

• History of allergy to iothalamate or history of renal failure due to contrast nephropathy

• Stroke or myocardial infarction within the preceding 12 months prior to randomization

• Coronary revascularization procedure within past 6 months

• Clinically apparent congestive heart failure defined as clinical signs of heart failure or an ejection fraction of < 40% (and/or depressed LV systolic function by echocardiogram).

• Terminal disease including cancer and AIDS

• Documented increase in serum creatinine > 50% of baseline within 3 months prior to the run-in period

• Renal disease known or in the opinion of the investigator caused by a condition other than diabetes

• Known adverse reaction to study medications including ACE inhibitors, ARB and spironolactone

• History of chronic or intermittent gross hematuria

• Spontaneous 24-hour urine sodium excretion rate exceeding 350 mEq/day

• AST or ALT greater than 2.5 the upper limit of normal for the laboratory

• Pregnancy

• History of autoimmune disease, connective tissue disease or multiple drug allergies

• Anticipated need for renal replacement therapy within 12 months Inclusion criteria for normal subjects

• Adult male and female subjects aged 20-65 of all ethnic backgrounds Exclusion criteria for normal subjects

• Chronic medical conditions, including but not limited to diabetes mellitus, hypertension, chronic kidney disease, and hyperlipidemia.

• Use of medications for antihypertensive

• Inability to follow study protocol for any reason