NCT01837108

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
14

participants targeted

Target at below P25 for phase_4

Timeline
Completed

Started Apr 2013

Shorter than P25 for phase_4

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2013

Completed
11 days until next milestone

First Submitted

Initial submission to the registry

April 12, 2013

Completed
10 days until next milestone

First Posted

Study publicly available on registry

April 22, 2013

Completed
7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2013

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2014

Completed
Last Updated

January 9, 2014

Status Verified

April 1, 2013

Enrollment Period

8 months

First QC Date

April 12, 2013

Last Update Submit

January 8, 2014

Conditions

Pharmacodynamics

Keywords

healthy

Outcome Measures

Primary Outcomes (1)

  • 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

Secondary Outcomes (2)

  • forearm blood flow

    8 days

  • forearm blood flow

    8 days

Other Outcomes (1)

  • 24 hours urine sample

    1 day

Study Arms (2)

Placebo

PLACEBO COMPARATOR

fully mimicking placebo 50 mg bid during 8 days

Drug: Placebo

eplerenone

EXPERIMENTAL

eplerenone 50 mg bid during 8 days

Drug: Eplerenone

Interventions

EplerenoneDRUG

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

Also known as: Inspra, RVG 29963
eplerenone
PlaceboDRUG
Placebo

Eligibility Criteria

Age18 Years - 40 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Radboud University Medical Centre

Nijmegen, Gelderland, 6525EZ, Netherlands

Location

Related Publications (1)

  • 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.

    PMID: 25356826DERIVED

MeSH Terms

Interventions

Eplerenone

Intervention Hierarchy (Ancestors)

LactonesOrganic ChemicalsPregnenesPregnanesSteroidsFused-Ring CompoundsPolycyclic Compounds

Study Officials

  • Niels Riksen, Dr.

    Radboud University Medical Centre Nijmegen

    PRINCIPAL INVESTIGATOR

  • Gerard Rongen, Prof.

    Radboud University Medical Centre Nijmegen

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 12, 2013

First Posted

April 22, 2013

Study Start

April 1, 2013

Primary Completion

December 1, 2013

Study Completion

January 1, 2014

Last Updated

January 9, 2014

Record last verified: 2013-04

Locations

NL(1)