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Is Augmentation of PORH by Rosuvastatin Adenosine-receptor Mediated?

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ClinicalTrials.gov Identifier: NCT00851175
Recruitment Status : Completed
First Posted : February 25, 2009
Last Update Posted : October 1, 2009
Sponsor:
Information provided by:
Radboud University

Study Description
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Brief Summary:

Rationale:

Statins form a class of drugs that is widely prescribed for hypercholesterolaemia, specifically to reduce the risk on atherosclerosis by lowering LDL-cholesterol. Next to the effect for which the drug was originally developed, it became obvious that statins have several other beneficial effects. Such pleiotropic effects include the activation of ecto-5'-nucleotidase which can increase endogenous adenosine production (by dephosphorylation adenosine monophosphate into adenosine) and subsequently cause vasodilation. A recent study of Meijer et al (not yet published) showed that rosuvastatin significantly augments vasodilation after a brief period of ischemia (post occlusive reactive hyperaemia). However, it is not yet verified whether this increase in post occlusive reactive hyperaemia is truly caused by a rise of extracellular adenosine and subsequent adenosine receptor stimulation. In this study, the mechanism by which rosuvastatin augments post occlusive reactive hyperaemia will be investigated by blocking adenosine receptors with caffeine, a competitive A1 and A2 adenosine receptor antagonist. Caffeine is a substance that can be safely used in normal concentrations to block the adenosine receptor.

Hypothesis:

The augmenting effect of rosuvastatin on PORH is caused by an increase of extracellular adenosine formation and this effect can be diminished by blocking the adenosine receptor using caffeine.

Objective:

To study the influence of caffeine on post occlusive reactive hyperaemia before and after 7 days treatment with rosuvastatin.

Study design:

Open label cross-over design Study population: Healthy volunteers, 18-50 years of age

Intervention:

Eight volunteers will receive a 7 day treatment with rosuvastatin 20 mg daily before and after rosuvastatin treatment caffeine will be administrated intra-arterially.

Main study parameters/endpoints:

Forearm blood flow (FBF) will be measured as an indicator for post occlusive reactive hyperaemia (PORH).


Condition or disease Intervention/treatment Phase
Atherosclerosis Cardiovascular Disease Drug: rosuvastatin Drug: caffeine Phase 4

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 8 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Is Augmentation of PORH by Rosuvastatin Adenosine-receptor Mediated?
Study Start Date : March 2009
Actual Primary Completion Date : August 2009
Actual Study Completion Date : September 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Caffeine

Arms and Interventions
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Arm Intervention/treatment
No Intervention: 1
forearm bloodflow after 2,3, and 5 minutes of forearm ischemia
Active Comparator: 2
forearm bloodflow after 2,3, and 5 minutes of forearm ischemia with concommitant administration of caffeine (90 ug/min/100ml forearm volume) into the brachial artery of the experimental (=non dominant) arm
 Drug: caffeine
intra-arterial (brachial artery of non dominant arm) administration of caffeine(90 ug/min/100ml forearm volume)for approximately 60 minutes
Experimental: 3
forearm bloodflow after 2,3, and 5 minutes of forearm ischemia after 7 days oral treatment with rosuvastatin 1dd 20mg
 Drug: rosuvastatin
7 day treatment with rosuvastatin 1dd 20mg
Active Comparator: 4
forearm bloodflow after 2,3, and 5 minutes of forearm ischemia after 7 days oral treatment with rosuvastatin 1dd 20mg with concommitant administration of caffeine (90 ug/min/100ml forearm volume) into the brachial artery of the experimental (=non dominant) arm
 Drug: rosuvastatin
7 day treatment with rosuvastatin 1dd 20mg

Drug: caffeine
intra-arterial (brachial artery of non dominant arm) administration of caffeine(90 ug/min/100ml forearm volume)for approximately 60 minutes


Outcome Measures
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Primary Outcome Measures :
  1. Forearm blood flow (FBF)after 2, 5, and 13 minutes of forearm ischemia [ Time Frame: before and after 7 day treament with rosuvastatin, with and without concommitant intra-arterial treatment with caffeine ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age 18-50
  • Written informed consent

Exclusion Criteria:

  • History of any cardiovascular disease
  • Hypertension (in supine position: systole >140 mmHg, diastole >90 mmHg)
  • Diabetes Mellitus (fasting glucose >7.0 mmol/L or random glucose >11.0 mmol/L)
  • Hyperlipidemia (fasting total cholesterol >5.5 mmol/L or random cholesterol >6.5 mmol/L)
  • Alanine amino transferase >90 U/L
  • Creatin kinase >440 U/L
  • Raised rhabdomyolysis risk (GFR <80 ml/min and/or overt clinical signs of hypothyroidism and/or myopathy in family history
  • Alcohol abuse
  • Concommitant chronic use of medication
  • Participation to any drug-investigation during the previous 60 days as checked with VIP check
Contacts and Locations
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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): NCT00851175


Locations
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Netherlands
RUNMC
Nijmegen, Netherlands, 6525 GA
Sponsors and Collaborators
Radboud University
Investigators
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Principal Investigator: G Rongen, MD PhD RUNMC
More Information
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Publications:

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Responsible Party: G. Rongen MD PhD, RUNMC
ClinicalTrials.gov Identifier: NCT00851175    
Other Study ID Numbers: rosucaff2
First Posted: February 25, 2009    Key Record Dates
Last Update Posted: October 1, 2009
Last Verified: March 2009
Additional relevant MeSH terms:
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Atherosclerosis
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Adenosine
Caffeine
Rosuvastatin Calcium
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
 Central Nervous System Stimulants
Physiological Effects of Drugs
Phosphodiesterase Inhibitors
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Arrhythmia Agents
Vasodilator Agents
Purinergic P1 Receptor Agonists
Purinergic Agonists