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
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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 |
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Atherosclerosis Cardiovascular Disease | Drug: rosuvastatin Drug: caffeine | Phase 4 |
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 |
Arm | Intervention/treatment |
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No Intervention: 1
forearm bloodflow after 2,3, and 5 minutes of forearm ischemia
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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
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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
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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
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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 |
- 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 ]

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

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
Netherlands | |
RUNMC | |
Nijmegen, Netherlands, 6525 GA |
Principal Investigator: | G Rongen, MD PhD | RUNMC |
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 |
Cardiovascular Diseases Atherosclerosis Arteriosclerosis Arterial Occlusive Diseases Vascular Diseases 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 |