Background: Microalbuminuria is an early marker of diabetic nephropathy, and its prevention can be considered to be the primary prevention of diabetic nephropathy. Angiotensin converting enzyme inhibitors and non-dihydropyridinic calcium antagonists have specific renoprotective properties in diabetes, and preliminary evidence is available that their combination can delay the onset and limit the progression of nephropathy in experimental diabetes more effectively than either of the two agents alone.
Design of clinical trial: The Bergamo Nephrologic Diabetes Complication Trial is a prospective, randomized, double-blind, parallel-group study aimed at evaluating the possibility of preventing the onset of nephropathy in 2400 hypertensive non-insulin-dependent diabetes mellitus patients who have a normal albumin excretion rate. During phase A of the study, patients will be randomized to one of the following treatments for 3 years: a non-dihydropyridinic calcium antagonist (slow-release verapamil 240 mg/day), an angiotensin converting enzyme inhibitor (trandolapril 2 mg/day), the combination of these drugs (verapamil 180 mg/day plus trandolapril 2 mg/day) and placebo. Other antihypertensive agents will be allowed in order to achieve and maintain systolic and diastolic blood pressures consistently below 140 and 90 mmHg, respectively, in all patients. The primary efficacy variable of phase A will be progression to microalbuminuria. In phase B progression to macro-albuminuria will be evaluated in patients who became microalbuminuric in phase A. These patients will be randomized to 2 years of treatment with trandolapril (2 mg/day) alone or combined with verapamil (180 mg/day).