Eplerenone and Extracellular Adenosine Formation (eplerenone01)
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|ClinicalTrials.gov Identifier: NCT01837108|
Recruitment Status : Completed
First Posted : April 22, 2013
Last Update Posted : January 9, 2014
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.
|Condition or disease||Intervention/treatment||Phase|
|Pharmacodynamics||Drug: Eplerenone Drug: Placebo||Phase 4|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||14 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Primary Purpose:||Basic Science|
|Official Title:||Effects of the Selective Mineralocorticoid Receptor Antagonist Eplerenone on Extracellular Adenosine Formation in Humans in Vivo|
|Study Start Date :||April 2013|
|Actual Primary Completion Date :||December 2013|
|Actual Study Completion Date :||January 2014|
Placebo Comparator: Placebo
fully mimicking placebo 50 mg bid during 8 days
eplerenone 50 mg bid during 8 days
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
Other Name: Inspra, RVG 29963
- 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.
- forearm blood flow [ Time Frame: 8 days ]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.
- forearm blood flow [ Time Frame: 8 days ]Forearm blood flow to incremental periods of arterial occlusion. The forearm blood flow will be measured by plethysmography.
- 24 hours urine sample [ Time Frame: 1 day ]Twenty-four hours urine samples will be collected and sodium and creatinine will be determined, to ensure that salt intake is approximately the same during both treatment days.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01837108
|Radboud University Medical Centre|
|Nijmegen, Gelderland, Netherlands, 6525EZ|
|Principal Investigator:||Niels Riksen, Dr.||Radboud University Medical Centre Nijmegen|
|Study Chair:||Gerard Rongen, Prof.||Radboud University Medical Centre Nijmegen|