To study the influence of caffeine on post occlusive reactive hyperaemia before and after 7 days treatment with rosuvastatin.
ID
Source
Brief title
Condition
- Other condition
- Coronary artery disorders
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Health condition
ischemie
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Forearm blood flow (FBF) will be measured as an indicator for post occlusive
reactive hyperaemia (PORH).
Secondary outcome
effect of 7 day treatment with rosuvastatin on lipid profile
Background summary
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 medium that can be safely used in normal concentrations to block
the adenosine receptor. Thus, if the augmenting effect of rosuvastatin on PORH
is caused by an increase of extracellular adenosine formation, this effect can
be diminished by blocking the adenosine receptor using caffeine.
Study 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
Intervention
Eight volunteers will receive a 7 day treatment with rosuvastatin 20 mg daily.
Study burden and risks
Treatment with rosuvastatin is not expected to harm the volunteers. Most
reported side effects of rosuvastatin are gastro-intestinal complains and
myalgia. The volunteers will not benefit directly from participating in this
study.
Postbus 9101
6500 HB Nijmegen
Nederland
Postbus 9101
6500 HB Nijmegen
Nederland
Listed location countries
Age
Inclusion criteria
Healthy volunteers, 18-50 years of age
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 total cholesterol >6.5 mmol/L)
Alanine amino transferase >90 U/L
Creatin kinase >440 U/L
Raised rabdomyolysis risk
GFR <80 ml/min
overt clinical signs of hypothyroidism
Myopathy in family history
Alcohol abuse
Concomitant chronic use of medication
Participation to any drug-investigation during the previous 60 days as checked with VIP check according to CRCN standard procedures.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2008-005985-30-NL |
| CCMO | NL25101.091.08 |