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Trial record 89 of 1176 for:    adenosine

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
Sponsor:
Information provided by (Responsible Party):
Radboud University

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.


Condition or disease Intervention/treatment Phase
Pharmacodynamics Drug: Eplerenone Drug: Placebo Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: Randomized
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo
fully mimicking placebo 50 mg bid during 8 days
Drug: Placebo
Experimental: eplerenone
eplerenone 50 mg bid during 8 days
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
Other Name: Inspra, RVG 29963




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.


Other Outcome Measures:
  1. 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.



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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

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


Locations
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Netherlands
Radboud University Medical Centre
Nijmegen, Gelderland, Netherlands, 6525EZ
Sponsors and Collaborators
Radboud University
Investigators
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Principal Investigator: Niels Riksen, Dr. Radboud University Medical Centre Nijmegen
Study Chair: Gerard Rongen, Prof. Radboud University Medical Centre Nijmegen

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT01837108     History of Changes
Other Study ID Numbers: NL43234.091.13
First Posted: April 22, 2013    Key Record Dates
Last Update Posted: January 9, 2014
Last Verified: April 2013
Keywords provided by Radboud University:
healthy
Additional relevant MeSH terms:
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Adenosine
Eplerenone
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Vasodilator Agents
Purinergic P1 Receptor Agonists
Purinergic Agonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Diuretics, Potassium Sparing
Diuretics
Natriuretic Agents
Antihypertensive Agents