Eplerenone and Extracellular Adenosine Formation

Pharmacodynamics Clinical Trial

— eplerenone01  

Official title:

Effects of the Selective Mineralocorticoid Receptor Antagonist Eplerenone on Extracellular Adenosine Formation in Humans in Vivo

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01837108
• Other study ID #: NL43234.091.13
• Status: Completed
• Phase: Phase 4
• First received: April 12, 2013
• Last updated: January 8, 2014
• Start date: April 2013
• Est. completion date: January 2014

Study information

• Verified date: April 2013
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical 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, 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: January 2014
• Est. primary completion date: December 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 40 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Pharmacodynamics

Intervention

Drug:
• Eplerenone
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
• Placebo

Locations

Country	Name	City	State
Netherlands	Radboud University Medical Centre	Nijmegen	Gelderland

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	24 hours urine sample	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.	1 day	No
Primary	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.	8 days	No
Secondary	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.	8 days	No
Secondary	forearm blood flow	Forearm blood flow to incremental periods of arterial occlusion. The forearm blood flow will be measured by plethysmography.	8 days	No