Clinical Trial: Eplerenone, ACE Inhibition and Albuminuria

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Eplerenone, ACE Inhibition and Albuminuria

Brief Summary: The purpose of this study is to determine whether eplerenone is more effective than doubling the dose of ACE inhibitor in reducing urinary protein (albumin) loss in diabetes mellitus

Detailed Summary:

In patients with proteinuric renal diseases renal function almost invariably deteriorates, independent from the original renal disease. It has been demonstrated that the rapidity of renal function deterioration is determined by blood pressure and proteinuria1. Treatment modalities that lower proteinuria in general tend to attenuate the deterioration of renal function. As such, ACE-inhibitors have been proven to be of particular value in the treatment of patients with proteinuria, since these drugs consistently lower proteinuria. More recently, similar antiproteinuric effects have been described for the angiotensin receptor blockers (ARBs). Theoretically, ACE inhibitors may have advantages over ARBs because they are supposed to increase bradykinin levels. Bradykinin has also been implicated in the development of nephropathy in mice. About its role in human diabetic nephropathy few if any data exist. The effect of ACE inhibition or ARBs is not complete, since addition of either drug to the other may further improve albuminuria. This may be explained by insufficient dosage of single drug therapy or because of an escape phenomenon. The latter has been amply described for ACE inhibitors. Especially with chronic ACE inhibition angiotensin II levels may be near normal. This may lead to persistent angiotensin II effects, among which aldosterone stimulation.

Even though most investigators have emphasized the role of the renin-angiotensin system in progressive renal injury, aldosterone has received little attention. However, its profibrotic effects make aldosterone a potentially important player in the field, even more so because the escape of aldosterone during treatment with ACE-inhibitors or ARBs. Moreover, in addition to these theoretical considerations, evidence is emerging that mineralocorticoid receptor blockade with spironolactone added to ACE-inhibitors or ARBs indeed has
Sponsor: Radboud University

Current Primary Outcome:

  • proteinuria [ Time Frame: 0, 4, 12, 24 and 30 weeks ]
  • blood pressure by home measurements [ Time Frame: 0, 4, 12, 24 and 30 weeks ]


Original Primary Outcome:

  • proteinuria
  • blood pressure measured by ABPM
  • differential protein excretion in 2 hr urines (b2-microglobulin, GST etc.)
  • GFR and RPF


Current Secondary Outcome:

  • serum potassium [ Time Frame: 0, 3, days, 2, 4, 12, 24 and 30 weeks ]
  • haemoglobin [ Time Frame: 0, 4, 12, 24 and 30 weeks ]
  • urinary excretion of CTGF, TGF-b, collagen IV [ Time Frame: 0, 4, 12, 24 and 30 weeks ]
  • inulin and PAH clearance [ Time Frame: 0, 24 and 30 weeks ]
  • Quality of Life [ Time Frame: 0, 4, 12, 24 and 30 weeks ]
  • plasma aldosterone, renin [ Time Frame: 0, 24 and 30 weeks ]
  • plasma angiotensins and bradykinins [ Time Frame: 0, 24 and 30 weeks ]


Original Secondary Outcome:

  • serum potassium
  • haemoglobin
  • urinary excretion of CTGF, TGF-b, collagen IV
  • endothelial function of forearm
  • Quality of Life
  • plasma aldosterone, renin
  • plasma angiotensins and bradykinins
  • endogenous hippuric acid clearance


Information By: Radboud University

Dates:
Date Received: April 14, 2006
Date Started: January 2007
Date Completion:
Last Updated: May 25, 2012
Last Verified: May 2012