Design and methods for a double blind, randomized study of tolrestat for the prevention of nephropathy in normotensive patients with insulin-dependent diabetes mellitus and microalbuminuria

Abstract

This article describes the design and methods for a multicenter, double-blind, randomized, placebo-controlled trial being conducted to determine the efficacy and safety of an aldose reductase inhibitor, tolrestat, for the prevention of nephropathy in normotensive patients with insulin-dependent (type I) diabetes mellitus. Patients with type I diabetes mellitus of greater than 5 years' duration were enrolled if they had a baseline urinar albumin excretion rate (UAER) within 10 to 150 μg/min; a mean supine diastolic blood pressure <90 mm Hg; and a glomerular filtration rate ⩾80 mL/min/1.73 m 2. Patients were randomly assigned to one of three parallel treatment groups: placebo twice daily, tolrestat 200 mg once daily and placebo once daily, or tolrestat 200 mg twice daily. The minimum treatment period is 48 months. The primary efficac end point will be the change in UAER over time; a secondary end point will be the change in diastolic blood pressure over time. This study represents the first large-scale, long-term controlled trial undertaken to assess the efficacy of an aldose reductase inhibitor for prevention of progression of microalbuminuria in diabetic patients. When completed, this study should provide valuable information about the the efficacy of an aldose reductase inhibitor, tolrestat, for the prevention of diabetic nephropathy.