Is Augmentation of PORH by Rosuvastatin Adenosine-receptor Mediated?

This study has been completed.
Sponsor:
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT00851175
First received: February 24, 2009
Last updated: September 30, 2009
Last verified: March 2009
  Purpose

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 Intervention Phase
Atherosclerosis
Cardiovascular Disease
Drug: rosuvastatin
Drug: caffeine
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Is Augmentation of PORH by Rosuvastatin Adenosine-receptor Mediated?

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 8
Study Start Date: March 2009
Study Completion Date: September 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00851175

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

Publications:
Responsible Party: G. Rongen MD PhD, RUNMC
ClinicalTrials.gov Identifier: NCT00851175     History of Changes
Other Study ID Numbers: rosucaff2
Study First Received: February 24, 2009
Last Updated: September 30, 2009
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Netherlands: Medical Ethics Review Committee (METC)

Additional relevant MeSH terms:
Arteriosclerosis
Atherosclerosis
Cardiovascular Diseases
Arterial Occlusive Diseases
Vascular Diseases
Caffeine
Rosuvastatin
Anticholesteremic Agents
Antimetabolites
Central Nervous System Agents
Central Nervous System Stimulants
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Phosphodiesterase Inhibitors
Physiological Effects of Drugs
Purinergic Agents
Purinergic Antagonists
Purinergic P1 Receptor Antagonists
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014