Clinical trial NCT00340678
Conditions: Diabetic Nephropathy
Keywords: Angiotensin II Receptor Antagonist Therapeutic Trial Glomerular Filtration Rate Kidney Biopsy Non-Insulin Dependent Diabetes Mellitus
Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Start date: 1995-08-01; Completion date: 2014-03-01
Enrollment: 170 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This investigation is a randomized, double-blinded, placebo-controlled clinical trial in adult diabetic Pima Indians with normal urinary albumin excretion (albumin-to-creatinine ration less than 30 mg/g) or microalbuminuria (albumin-to-creatinine ration = 30-299 mg/g) to test the hypothesis that blockade of the renin-angiotensin system with the angiotensin receptor blocker (ARB) losartan can prevent or further attenuate the development and progression of early diabetic nephropathy in subjects with type 2 diabetes mellitus who are receiving standard diabetes care.

One hundred seventy subjects were recruited for the study, all of whom had type 2 diabetes for at least 5 years, serum creatinine concentrations less than 1.4 mg/dl, and no evidence of non-diabetic renal diseases. Ninety-two of the subjects had normal urinary albumin excretion at baseline and other 78 had microalbuminuria. Subjects in each albumin excretion group were randomized to treatment with either the angiotensin II receptor antagonist, losartan, or placebo. Measurements of glomerular filtration rate (GFR), renal plasma flow (RPF) and fractional clearances of albumin and IgG will be made initially, at one month, and at 12-month intervals from baseline thereafter. A kidney biopsy was performed after six years in 111 subjects. Morphometric analysis of renal biopsies was used to determine differences in glomerular structure between treatment groups.

Detailed description:
This investigation is a randomized, double-blinded, placebo-controlled clinical trial in adult diabetic Pima Indians with normal urinary albumin excretion (albumin-to-creatinine ratio \< 30 mg/g) or microalbuminuria (albumin-to-creatinine ratio = 30-299 mg/g) to test the hypothesis that blockade of the renin-angiotensin system with the angiotensin receptor blocker (ARB) losartan can prevent or further attenuate the development and progression of early diabetic nephropathy in subjects with type 2 diabetes mellitus who are receiving standard diabetes care.

One hundred seventy subjects were recruited for the study, all of whom had type 2 diabetes for at least 5 years, serum creatinine concentrations \< 1.4 mg/dl, and no evidence of non-diabetic renal diseases. Ninety-two of the subjects had normal urinary albumin excretion at baseline and the other 78 had microalbuminuria. Subjects in each albumin excretion group were randomized to treatment with either the angiotensin II receptor antagonist, losartan, or placebo. Measurements of glomerular filtration rate (GFR), renal plasma flow (RPF) and fractional clearances of albumin and immunoglobulin G (IgG) were made initially, at one month, and at 12-month intervals from baseline thereafter. A kidney biopsy was be performed after six years in 111 subjects. Morphometric analysis of renal biopsies was used to determine differences in glomerular structure between treatment groups.

The major outcome measure was a decline in GFR to less than or equal to 60 ml/min or to half the baseline value in subjects that enter the study with a GFR of \< 120 ml/min. Other measures of renoprotection were assessed, including group differences in 1) change in albumin excretion, 2) change in serum creatinine concentration, and 3) glomerular morphology in all subjects as outlined above.

Arms: arm 1: Subjects with normal urinary albumin excretion were treated with losartan began at 50 mg daily, with the dose increasing to 100 mg daily after 1 week if symptomatic hypotension did not develop. arm 2: Subjects with normal urinary albumin excretion were treated with placebo corresponding to each dose of losartan. arm 3: Subjects with microalbuminuria were treated with losartan began at 50 mg daily, with the dose increasing to 100 mg daily after 1 week if symptomatic hypotension did not develop. arm 4: Subjects with Microalbuminuria were treated with placebo corresponding to each dose of losartan.
Interventions: intervention 1: Losartan intervention 2: Placebo
Intervention descriptions: intervention 1: Treatment with losartan began at 50 mg daily, with the dose increasing to 100 mg daily after 1 week if symptomatic hypotension did not develop. intervention 2: Treatment with placebo corresponding to each dose of losartan.

Protocol documents: