To study the protective effect of pretreatment (both 3 day and 7 day) with rosuvastatin and atorvastatin on flow mediated dilation after 15 minutes ischemia and 15 minutes reperfusion.
ID
Source
Brief title
Condition
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Difference in flow mediated dilation before and after 15 minutes ischemia.
Secondary outcome
ecto-5*-nucleotidase activity after rosuvastatin and atorvastatin treatment (3
day and 7 day)
Background summary
Apart from their cholesterol lowering effects, statins have
cholesterol-independent pleiotropic actions, such as upregulation of 5*-
ectonucleotidase and up-regulation of NO-synthase that may increase tolerance
against ischemia-reperfusion injury (IR-injury). Several animal studies have
shown reduction of IR-injury as a result of statin treatment in both the heart
and the kidney. Recently we have shown, using Annexin A5 targeting after
voluntary ischemic exercise to assess IR-injury, a protective effect of a 7 day
oral rosuvastatin treatment. A three day treatment with atorvastatin however
failed to reduce annexin targeting.
Assessment of the flow mediated dilation of the brachial artery as measure of
endothelial (dys)function, is a validated model to research effects of possible
protective strategies and perform mechanistic experiments on IR-injury in
humans in vivo.
We hypothesize that pretreatment with statins can increase endothelial
tolerance against ischemia and reperfusion injury.
Study objective
To study the protective effect of pretreatment (both 3 day and 7 day) with
rosuvastatin and atorvastatin on flow mediated dilation after 15 minutes
ischemia and 15 minutes reperfusion.
Study design
placebo-controlled randomised double-blind trial
Intervention
Treatment with either rosuvastatin 20 mg, atorvastatin 80mg or placebo during
either 3 or 7 days
Study burden and risks
Treatment with rosuvastatin or atorvastatin is not expected to harm the
volunteers. Most reported side effects of rosuvastatin and atorvastatin 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
- Age 18-50
- Written informed consent
Exclusion criteria
- Smoking
- 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
- Creatine kinase >440 U/L
- Raised rabdomyolysis risk
o GFR <60 ml/min
o Overt clinical signs of hypothyroidism
o Myopathy in family history
o Alcohol abuse
- Concomitant chronic use of medication
- Participation to any drug-investigation during the previous 60 days as checked with VIP check.
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 | EUCTR2009-014831-18-NL |
| CCMO | NL29271.091.09 |