healthy volunteers
Conditions
Interventions
Trade Name: Inspra
Pharmaceutical Form: Capsule
INN or Proposed INN: eplerenone
Other descriptive name: EPLERENONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1
Sponsors
University Medical Centre Nijmegen
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: male sex, age 18-40 years, healthy, written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 14 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: potassium >4.8 mmol/L, smoking, hypertension (SBP >140 or DBP >90 mmHg), hypotension (SBP 7.0 mmol/L or random >11.0 mmol/L), history of any cardiovascular disease, angina pectoris, history of COPD or asthma, alcohol and/or drug abuse, concomitant use of medication, renal dysfunction (MDRD twice upper limit), fasting total cholesterol >6 mmol/L, 2nd/3rd degree AV block on electrocardiography. During the study a serum potassium of >5.2 mmol/L is an exclusion criterium.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To study whether the mineralocorticoid receptor antagonist eplerenone activates CD73 and hereby increases extracellular formation of adenosine in humans in vivo, by using the forearm vasodilator respons to the intrabrachial administration of the ENT-inhibitor dipyridamole, as a surrogate for adenosine stimulation;Secondary Objective: The effect of eplerenone on the forearm vasodilator response to arterial occlusion (post occlusive reactive hyperemia);Primary end point(s): forearm blood flow (measured with venous plethysmography). The forearm blood flow respons will be measured during usage of eplerenone and during usage of placebo to: 1) administration of incremental dosages of dipyridamole into the brachial artery (as a surrogate for adenosine formation) 2) 2 and 5 minutes of arterial occlusion (post occlusive reactive hyperemia), because this is known to stimulate adenosine formation 3) co-administration of dipyridamole and caffeine. Dipyridamole increases adenosine formation and this effect is blocked by caffeine. 4) two different concentrations of adenosine and sodium-nitroprusside. These substances serve as negative control and exclude non-specific effects of eplerenone on vascular reactivity or adenosine sensitivity. ;Timepoint(s) of evaluation of this end point: 7 days after start of eplerenone or placebo, the experiments will be performed. Because not all experiments can be done on the same day, forearm blood flow response to adenosine and sodium-nitroprusside will be performed 8 days after start of eplerenone. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): not applicable (see E.5.1.1);Timepoint(s) of evaluation of this end point: not applicable | — |
Countries
Netherlands
Contacts
Public ContactDep. of Farmacology-toxicology
University Medical Centre Nijmegen
Outcome results
None listed