Diabetic NephropathyPhase 2NCT00315016
Eplerenone, ACE Inhibition and Albuminuria
A Phase 2 study testing eplerenone and fosinopril in people with Diabetic Nephropathy, run by Radboud University Medical Center at 2 sites in Netherlands.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Diabetic Nephropathy
- What is being tested?
- eplerenone and fosinopril
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 2 sitesNetherlands
- Study dates
- Jan 2007to Jul 2011
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- documented diabetic renal disease with albuminuria >0.020 g/L, stable renal function (i.e. increase of serum creatinine <25% / 6 months), creatinine clearance > 40 ml/min/1.73 m2 , in spite of maximal ACE-inhibition (40 mg fosinopril/day)
- blood pressure < 140/90 mm Hg ( at baseline)
- serum potassium < 5.0 mmol/l (at baseline).
Who cannot join
- use of NSAID's or immunosuppressive drugs
- use of ARBs, intolerance for ACE inhibition.
- use of diuretics that increase potassium such as triamterene, spironolactone or eplerenone
- pregnancy
- rash or cough on one on the drugs
- severe heart disease or instable angina
Trial locations and contacts
2 sites in 1 country.
Netherlands2 sites
Jeroen Bosch Hospital
's-Hertogenbosch, North Brabant
University Medical Center Nijmegen St Radboud
Nijmegen, 6525 GA
About this study
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
Read the detailed description
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:
- 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.
- Conditions
- Diabetic Nephropathy
- Being tested
- eplerenone, fosinopril, placebo
- Keywords
- albuminuria, eplerenone, ACE inhibition, renal function, endothelial function
- Medical subject headings
- Diabetic Nephropathies, Albuminuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
eplerenoneDrug
Also called Eplerenone or INSPRA
active comparator
fosinoprilDrug
Also called fosinopril or Newace
doubling of fosinopril dose
placeboDrug
Also called no other name
placebo (double dummy)
| Study group | Role | What they receive |
|---|---|---|
| 1 | Placebo comparator | placebo (double dummy) Receives: Drug: placebo |
| 2 | Active comparator | eplerenone Receives: Drug: eplerenone |
| 3 | Active comparator | doubling of fosinopril dose Receives: Drug: fosinopril |
What is being measured
The primary outcome is the main question the study is designed to answer.
proteinuria
Measured: 0, 4, 12, 24 and 30 weeks
blood pressure by home measurements
Measured: 0, 4, 12, 24 and 30 weeks
Secondary outcomes (7)
serum potassium
Measured: 0, 3, days, 2, 4, 12, 24 and 30 weeks
haemoglobin
Measured: 0, 4, 12, 24 and 30 weeks
urinary excretion of CTGF, TGF-b, collagen IV
Measured: 0, 4, 12, 24 and 30 weeks
inulin and PAH clearance
Measured: 0, 24 and 30 weeks
Quality of Life
Measured: 0, 4, 12, 24 and 30 weeks
plasma aldosterone, renin
Measured: 0, 24 and 30 weeks
plasma angiotensins and bradykinins
Measured: 0, 24 and 30 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2006 (estimated)
- Study startJan 2007
- Primary completionJul 2011
- Study completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetic NephropathyStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jacob Deinum, MD, Principal investigator, University Medical Center Nijmegen St Radboud, The Netherlands
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00315016
- Sponsor's protocol ID
- IRG 2005-316
- Status last verified
- May 2012
- First submitted
- 14 Apr 2006
- Last updated
- 28 May 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Chung EY, Ruospo M, Natale P, Bolignano D, Navaneethan SD, Palmer SC, Strippoli GF. Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2020 Oct 27;10(10):CD007004. doi: 10.1002/14651858.CD007004.pub4.
PubMed 33107592
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Eplerenone, ACE Inhibition and Albuminuria
- ClinicalTrials.gov ID
- NCT00315016
- Acronym / sponsor ID
- IRG 2005-316
- Conditions
- Diabetic Nephropathy
- Keywords
- albuminuria, eplerenone, ACE inhibition, renal function, endothelial function
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Jan 2007
- Primary completion
- Jul 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 17 Apr 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 description
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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Placebo comparator | Drug: placeboplacebo (double dummy) |
| 2 | Active comparator | Drug: eplerenoneeplerenone |
| 3 | Active comparator | Drug: fosinoprildoubling of fosinopril dose |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- documented diabetic renal disease with albuminuria >0.020 g/L, stable renal function (i.e. increase of serum creatinine <25% / 6 months), creatinine clearance > 40 ml/min/1.73 m2 , in spite of maximal ACE-inhibition (40 mg fosinopril/day)
- blood pressure < 140/90 mm Hg ( at baseline)
- serum potassium < 5.0 mmol/l (at baseline).
Key exclusion criteria (6 listed)
- use of NSAID's or immunosuppressive drugs
- use of ARBs, intolerance for ACE inhibition.
- use of diuretics that increase potassium such as triamterene, spironolactone or eplerenone
- pregnancy
- rash or cough on one on the drugs
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| eplerenoneAlso: Eplerenone or INSPRAactive comparator | Drug | 2 |
| fosinoprilAlso: fosinopril or Newacedoubling of fosinopril dose | Drug | 3 |
| placeboAlso: no other nameplacebo (double dummy) | Drug | 1 |
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
7 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2012.
- Derived from this study: PubMed 33107592Chung EY, Ruospo M, Natale P, Bolignano D, Navaneethan SD, Palmer SC, Strippoli GF. Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2020 Oct 27;10(10):CD007004. doi: 10.1002/14651858.CD007004.pub4.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jacob Deinum, MD principal investigator
University Medical Center Nijmegen St Radboud, The Netherlands
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing eplerenone and fosinopril in people with Diabetic Nephropathy, run by Radboud University Medical Center at 2 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 May 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
proteinuria (time frame: 0, 4, 12, 24 and 30 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00315016, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2012.