Is Augmentation of PORH by Rosuvastatin Adenosine-receptor Mediated?

Cardiovascular Disease Clinical Trial

Official title:

Is Augmentation of PORH by Rosuvastatin Adenosine-receptor Mediated?

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00851175
• Other study ID #: rosucaff2
• Status: Completed
• Phase: Phase 4
• First received: February 24, 2009
• Last updated: September 30, 2009
• Start date: March 2009
• Est. completion date: September 2009

Study information

• Verified date: March 2009
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)Netherlands: Medical Ethics Review Committee (METC)
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: September 2009
• Est. primary completion date: August 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Atherosclerosis
• Cardiovascular Disease
• Cardiovascular Diseases

Intervention

Drug:
• rosuvastatin
7 day treatment with rosuvastatin 1dd 20mg
• caffeine
intra-arterial (brachial artery of non dominant arm) administration of caffeine(90 ug/min/100ml forearm volume)for approximately 60 minutes

Locations

Country	Name	City	State
Netherlands	RUNMC	Nijmegen

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Country where clinical trial is conducted

Netherlands, 

References & Publications (2)

Bijlstra PJ, den Arend JA, Lutterman JA, Russel FG, Thien T, Smits P. Blockade of vascular ATP-sensitive potassium channels reduces the vasodilator response to ischaemia in humans. Diabetologia. 1996 Dec;39(12):1562-8. — View Citation

Meijer P, Wouters CW, van den Broek PH, Scheffer GJ, Riksen NP, Smits P, Rongen GA. Dipyridamole enhances ischaemia-induced reactive hyperaemia by increased adenosine receptor stimulation. Br J Pharmacol. 2008 Mar;153(6):1169-76. doi: 10.1038/bjp.2008.10. Epub 2008 Feb 11. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Forearm blood flow (FBF)after 2, 5, and 13 minutes of forearm ischemia		before and after 7 day treament with rosuvastatin, with and without concommitant intra-arterial treatment with caffeine	No