Eplerenone and Extracellular Adenosine Formation (eplerenone01)

Radboud University Medical Center

Status and phase: Completed; Phase 4

Conditions: Pharmacodynamics

Treatments: Drug: Eplerenone; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT01837108

NL43234.091.13

Details and patient eligibility

About

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.

Enrollment: 14 patients

Sex: Male

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Male sex
• Age 18-40 years
• Healthy
• Written informed consent

Exclusion criteria

• 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
• 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 design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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14 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

fully mimicking placebo 50 mg bid during 8 days

Treatment:

Drug: Placebo

eplerenone

Experimental group

Description:

eplerenone 50 mg bid during 8 days

Treatment:

Drug: Eplerenone