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| Sponsor: | Radboud University |
|---|---|
| Information provided by: | Radboud University |
| ClinicalTrials.gov Identifier: | NCT00315016 |
Purpose
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
| Condition | Intervention | Phase |
|---|---|---|
|
Diabetic Nephropathy |
Drug: eplerenone Drug: fosinopril Drug: placebo |
Phase II |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment |
| Official Title: | Eplerenone, ACE Inhibition and Albuminuria |
| Estimated Enrollment: | 72 |
| Study Start Date: | January 2007 |
| Estimated Study Completion Date: | December 2010 |
| Estimated Primary Completion Date: | July 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Placebo Comparator: 1
placebo (double dummy)
|
Drug: placebo
placebo (double dummy)
Other Name: no other name
|
|
Active Comparator: 2
eplerenone
|
Drug: eplerenone
active comparator
Other Name: Eplerenone or INSPRA
|
|
Active Comparator: 3
doubling of fosinopril dose
|
Drug: fosinopril
doubling of fosinopril dose
Other Name: fosinopril or Newace
|
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 an additive, favourable effect on proteinuria. These findings warrant a search for the value of such agents in albuminuria and exploration of the mechanisms by which mineralocorticoid blockade may exert its beneficial effects.
Primary aim:
1. To study whether the combination of eplerenone and a standard dose of ACE-inhibition has an additive effect on albuminuria in patients with albuminuric nephropathy compared to ACE-I alone, or double dose of ACE-inhibitor.
Eligibility| Ages Eligible for Study: | 18 Years to 75 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contacts and Locations| Contact: Jacob Deinum, MD | 0031243618819 | j.deinum@aig.umcn.nl |
| Contact: Cornelis Kramers, MD | 0031243618819 | c.kramers@pharmtox.umcn.nl |
| Netherlands | |
| Jeroen Bosch Hospital | Recruiting |
| 's-Hertogenbosch, Noord Brabant, Netherlands | |
| Contact: Paetrick M Netten, MD | |
| Sub-Investigator: Paetrick M Netten, MD | |
| University Medical Center Nijmegen St Radboud | Recruiting |
| Nijmegen, Netherlands, 6525 GA | |
| Principal Investigator: Jacob Deinum, MD | |
| Sub-Investigator: Cornelis Kramers, MD | |
| Sub-Investigator: Gerald Vervoort, MD | |
| Principal Investigator: | Jacob Deinum, MD | University Medical Center Nijmegen St Radboud, The Netherlands |
More Information
| Responsible Party: | University Medical Center Nijmegen St Radboud, Radboud University Nijmegen |
| ClinicalTrials.gov Identifier: | NCT00315016 History of Changes |
| Other Study ID Numbers: | IRG 2005-316 |
| Study First Received: | April 14, 2006 |
| Last Updated: | December 1, 2008 |
| Health Authority: | Netherlands: Medicines Evaluation Board (MEB) |
|
albuminuria eplerenone ACE inhibition renal function endothelial function |
|
Albuminuria Diabetic Nephropathies Kidney Diseases Proteinuria Urination Disorders Urologic Diseases Urological Manifestations Signs and Symptoms Diabetes Complications Diabetes Mellitus Endocrine System Diseases Fosinopril Eplerenone Spironolactone |
Angiotensin-Converting Enzyme Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antihypertensive Agents Cardiovascular Agents Therapeutic Uses Aldosterone Antagonists Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Diuretics Natriuretic Agents |
