PharmacodynamicsPhase 4eplerenone01NCT01837108
Eplerenone and Extracellular Adenosine Formation
A Phase 4 study testing Eplerenone in people with Pharmacodynamics, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
Various studies have reported cardioprotective effects of mineralocorticoid receptor (MR) antagonists in the setting of an acute myocardial infarction. In a recent animal study, the protective effect of MR antagonists on infarct size was completely abolished in CD73 knock-out and adenosine A2b receptor knock-out mice… Read more about this study
- Who is it for?
- Ages 18 to 40 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Pharmacodynamics
- What is being tested?
- Eplerenone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 1 siteNetherlands
- Study dates
- Apr 2013to Jan 2014
- Phase
- Phase 4
- 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 40 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male sex
- Age 18-40 years
- Healthy
- Written informed consent
Who cannot join
- Smoking
- Hypertension (Blood pressure >140 mmHg and/or >90 mmHg - SBP/DBP-)
- Hypotension (Blood pressure <100 mmHg and/or <60 mmHg -SBP/DBP-)
- Diabetes Mellitus (fasting glucose > 6.9 mmol/L or random > 11.0 mmol/L in venous plasma)
- History of any cardiovascular disease
- Angina pectoris
Show all 14Show fewer
- History of chronic obstructive pulmonary disease (COPD) or asthma
- Alcohol and/or drug abuse
- Concomitant use of medication
- Renal dysfunction (MDRD < 60 ml/min/1.73 m2)
- Liver enzyme abnormalities (ALAT > twice upper limit of normality)
- Serum potassium ≥ 4.8 mmol/L
- Fasting total cholesterol > 6.0 mmol/L
- Second/third degree AV-block on electrocardiography
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Radboud University Medical Centre
Nijmegen, Gelderland, 6525EZ
About this study
Official title: Effects of the Selective Mineralocorticoid Receptor Antagonist Eplerenone on Extracellular Adenosine Formation in Humans in Vivo
Various studies have reported cardioprotective effects of mineralocorticoid receptor (MR) antagonists in the setting of an acute myocardial infarction. In a recent animal study, the protective effect of MR antagonists on infarct size was completely abolished in CD73 knock-out and adenosine A2b receptor knock-out mice, and by co-administration of adenosine receptor antagonists in rats. These findings suggest that extracellular formation of adenosine is crucial for this protective effect and that MR antagonists stimulate extracellular adenosine formation by the enzyme CD73.
To investigate whether eplerenone promotes adenosine receptor stimulation by activating CD73, the investigators will measure forearm blood flow in response to various dosages of dipyridamole with the use of plethysmography. Dipyridamole increases the extracellular endogenous adenosine concentration by inhibition of the ENT transporter and induces local vasodilation. Therefore, the vasodilator effect of dipyridamole accurately reflects extracellular adenosine formation by the CD73 enzyme.
- Conditions
- Pharmacodynamics
- Being tested
- Eplerenone, Placebo
- Keywords
- healthy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EplerenoneDrug
Also called Inspra, RVG 29963
2 tabs of eplerenone 25 mg will be over-encapsulated and a fully mimicking placebo will be provided by the department of clinical pharmacy of the Radboud University Medical Centre Nijmegen
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | fully mimicking placebo 50 mg bid during 8 days Receives: Drug: Placebo |
| eplerenone | Experimental | eplerenone 50 mg bid during 8 days Receives: Drug: Eplerenone |
What is being measured
The primary outcome is the main question the study is designed to answer.
forearm blood flow response
Forearm blood flow response to the intrabrachial administration of incremental dosages of dipyridamole, after treatment with eplerenone, compared to placebo. The forearm blood flow will be measured by plethysmography.
Measured: 8 days
Secondary outcomes (2)
forearm blood flow
Forearm blood flow response to the intrabrachial administration of incremental dosages of dipyridamole, with and without caffeine, after eplerenone treatment. The forearm blood flow will be measured by plethysmography.
Measured: 8 days
forearm blood flow
Forearm blood flow to incremental periods of arterial occlusion. The forearm blood flow will be measured by plethysmography.
Measured: 8 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2013 (estimated)
- Study startApr 2013
- Primary completionDec 2013
- Study completionJan 2014
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 PharmacodynamicsStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Niels Riksen, Dr., Principal investigator, Radboud University Medical Centre NijmegenGerard Rongen, Prof., Study chair, Radboud University Medical Centre Nijmegen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01837108
- Sponsor's protocol ID
- NL43234.091.13
- Acronym
- eplerenone01
- Status last verified
- Apr 2013
- First submitted
- 12 Apr 2013
- Last updated
- 9 Jan 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
van den Berg TN, Deinum J, Bilos A, Donders AR, Rongen GA, Riksen NP. The effect of eplerenone on adenosine formation in humans in vivo: a double-blinded randomised controlled study. PLoS One. 2014 Oct 30;9(10):e111248. doi: 10.1371/journal.pone.0111248. eCollection 2014.
PubMed 25356826
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of the Selective Mineralocorticoid Receptor Antagonist Eplerenone on Extracellular Adenosine Formation in Humans in Vivo
- ClinicalTrials.gov ID
- NCT01837108
- Acronym / sponsor ID
- eplerenone01 / NL43234.091.13
- Conditions
- Pharmacodynamics
- Keywords
- healthy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Apr 2013
- Primary completion
- Dec 2013 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 22 Apr 2013 (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.
Various studies have reported cardioprotective effects of mineralocorticoid receptor (MR) antagonists in the setting of an acute myocardial infarction. In a recent animal study, the protective effect of MR antagonists on infarct size was completely abolished in CD73 knock-out and adenosine A2b receptor knock-out mice, and by co-administration of adenosine receptor antagonists in rats. These findings suggest that extracellular formation of adenosine is crucial for this protective effect and that MR antagonists stimulate extracellular adenosine formation by the enzyme CD73.
To investigate whether eplerenone promotes adenosine receptor stimulation by activating CD73, the investigators will measure forearm blood flow in response to various dosages of dipyridamole with the use of plethysmography. Dipyridamole increases the extracellular endogenous adenosine concentration by inhibition of the ENT transporter and induces local vasodilation. Therefore, the vasodilator effect of dipyridamole accurately reflects extracellular adenosine formation by the CD73 enzyme.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebofully mimicking placebo 50 mg bid during 8 days |
| eplerenone | Experimental | Drug: Eplerenoneeplerenone 50 mg bid during 8 days |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Male sex
- Age 18-40 years
- Healthy
- Written informed consent
Key exclusion criteria (14 listed)
- Smoking
- Hypertension (Blood pressure >140 mmHg and/or >90 mmHg - SBP/DBP-)
- Hypotension (Blood pressure <100 mmHg and/or <60 mmHg -SBP/DBP-)
- Diabetes Mellitus (fasting glucose > 6.9 mmol/L or random > 11.0 mmol/L in venous plasma)
- History of any cardiovascular disease
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: Inspra, RVG 299632 tabs of eplerenone 25 mg will be over-encapsulated and a fully mimicking placebo will be provided by the department of clinical pharmacy of the Radboud University Medical Centre Nijmegen | Drug | eplerenone |
| Placebo | Drug | Placebo |
Primary outcome
forearm blood flow response
Time frame: 8 days
Forearm blood flow response to the intrabrachial administration of incremental dosages of dipyridamole, after treatment with eplerenone, compared to placebo. The forearm blood flow will be measured by plethysmography.
2 secondary outcomes
forearm blood flow
Time frame: 8 days
forearm blood flow
Time frame: 8 days
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 9 Jan 2014.
- Derived from this study: PubMed 25356826van den Berg TN, Deinum J, Bilos A, Donders AR, Rongen GA, Riksen NP. The effect of eplerenone on adenosine formation in humans in vivo: a double-blinded randomised controlled study. PLoS One. 2014 Oct 30;9(10):e111248. doi: 10.1371/journal.pone.0111248. eCollection 2014.
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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.
Niels Riksen, Dr. principal investigator
Radboud University Medical Centre Nijmegen
Gerard Rongen, Prof. study chair
Radboud University Medical Centre Nijmegen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Eplerenone in people with Pharmacodynamics, run by Radboud University Medical Center at 1 site 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 4 inclusion and 14 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 9 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
forearm blood flow response (time frame: 8 days). 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 NCT01837108, 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 9 Jan 2014.