Maximal Dose of Angiotensin Converting Enzyme (ACE) Inhibitor for Treatment of Diabetic Kidney Disease
Condition: Diabetes Mellitus, Type I; Diabetic Nephropathy
MeSH terms: Kidney Diseases; Diabetic Nephropathies; Diabetes Mellitus, Type 1
Study type: Interventional

Summary: 
      The primary aim is to evaluate the anti proteinuric effect of increasing doses of the ACE
      inhibitor, lisinopril: 20, 40 and 60 mg daily in type 1 diabetic patients with hypertension
      and diabetic nephropathy.

      The secondary aim is to evaluate the effect on blood pressure (24 hour ambulatory blood
      pressure) and kidney function (glomerular filtration rate (GFR)).

      The tertiary aim is to evaluate differences in response to treatment according to
      ACE/insertion/deletion (ID)-genotypes and other genetic variants in the genes of the renin
      angiotensin system.
    

Detailed description: 
      This is a randomized, double-blind cross-over study with three treatment periods consisting
      of 20, 40 and 60 mg lisinopril daily in random order. The endpoints of the study will be
      examined after each treatment period. There is no wash out between treatment periods. To
      minimize the risk of hypotension every treatment period starts with 20 mg lisinopril for two
      weeks. Thus, the risk of adverse effects is minimized and an increase in dose from 0 mg to 60
      mg lisinopril is avoided.

      The patients usual antihypertensive treatments will be stopped in a period of 8 weeks (wash
      out) before randomization. Since diuretic drugs will be needed by almost every patient in the
      study to avoid oedema all patients will be treated with lasix retard 60 - 120 mg daily.

      Patients:

      60 type 1 diabetic patients with diabetic nephropathy and hypertension (blood pressure > 135
      mm Hg systolic and/or 85 mm Hg diastolic).

      Methods:

      The endpoints of the study will be examined at baseline and after each treatment period
      corresponding to 8, 16, and 24 weeks after randomization. The following parameters are
      determined after each treatment period: Albuminuria (determined from three consecutive 24
      hours urine collections), kidney function (GFR - by plasma clearance of 51Cr-EDTA ), and 24
      hour ambulatory blood pressure (TM-2420/2421). Furthermore, the concentrations of TGF-ß,
      sodium, creatinine, and carbamide in the 24 hour urinary samples are determined. The plasma
      concentration of albumin, renin, angiotensin II, and aldosterone is measured.

      DNA is extracted from a blood sample and genetic variants in the renin-angiotensin system are
      measured including the ACE/ID genotype.

      Endpoints:

      Primary endpoint: albuminuria ; Secondary endpoints: blood pressure (24 hour ambulatory) and
      GFR; Tertiary: differences in response to treatment in patients with different ACE/ID and
      other renin angiotensin system genotypes.
    

Intervention name(s): Lisinopril
Intervention type(s): Drug
Intervention MeSH terms: Lisinopril
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double
Primary purpose: Prevention
Keywords: diabetic nephropathy; type 1 diabetes; albuminuria; hypertension