Primary Objective: The objective of this project is to explore the role of adenosine receptor stimulation in the protective effect of rosuvastatin against ischemia-reperfusion injury after ischemic exercise of the forearm.Secondary Objective(s):…
ID
Source
Brief title
Condition
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Annexin A5 targeting (% difference in radioactivity (counts per pixel) between
experimental and control thenar muscle after ischemic exercise, as a indicator
for ischemia reperfusion injury.
Secondary outcome
-Workload (product of 50% of the maximum forearm force and duration of the
ischemic exercise)
-The effect of one-week treatment of rosuvastatine 20mg once daily on lipid
spectrum.
-The caffeine serum concentration after 24 hour abstinence, and after infusion
of cafeine (4mg/kg) or placebo.
Background summary
Rosuvastatin is a proven cholesterol lowering medicine, which hereby is assumed
to achieve a reduction in cardiovascular events. Apart from it*s cholesterol
lowering action, rosuvastatin may also increase tolerance against
ischemia-reperfusion injury. In dogs rosuvastatin increases the endogenous
concentration of adenosine, by enhancing the activity of the enzyme ecto-5*-
nucleotidase, which converts adenosine monophosphate into adenosine. We
hypothesize that rosuvastatin increases tolerance against ischemia-reperfusion
injury by induction of ecto-5*-nucleotidase and thereby increasing adenosine
activity. This protective effect of rosuvastatin can be abbrogated by using the
adenosine receptor antagonist caffeine.
Study objective
Primary Objective: The objective of this project is to explore the role of
adenosine receptor stimulation in the protective effect of rosuvastatin against
ischemia-reperfusion injury after ischemic exercise of the forearm.
Secondary Objective(s): Workload (Half of the maximum arm force multiplied with
the duration of this exercise). The effect of one-week treatment of
rosuvastatine 20mg once daily on lipid spectrum. The caffeine serum
concentration after 24 hour abstinence and after infusion of caffeine 4mg/kg
or placebo.
Study design
This study is a randomized double-blind placebo-controlled trial
Intervention
24 healthy male volunteers receive a one week treatment with 20 mg rosuvastatin
daily. On day 7, after at least 24 hours of caffeine abstinence all volunteers
will be randomised to receive either placebo (n=12) or caffeine (4mg/kg, n=12)
intravenously in a double blind fashion. 30 Minutes after intravenous
administration both the groups will perform ischemic isometric muscle
contraction of the non dominant forearm. Thereafter 99mTc labelled Annexin A5
will be administered intravenously and gamma scans will be made of both hands
after 60 en 240 minutes.
Study burden and risks
Treatment with rosuvastatin, caffeine or placebo is not expected to harm the
volunteers. Most reported side effects of rosuvastatin are gastro-intestinal
complains and myalgia. Ischemic hand gripping will temporarily result in pain
in the forearm. This is completely reversible upon reperfusion. 24 Hours of
caffeine abstinence can lead to mild headache. Administration of radiolabeled
Annexin A5 results in an effective dose of less than 5 mSv, well within the
range of accepted exposure to radioactivity for human research. Occurrence of
an allergic reaction is theoretically possible upon administration of Annexin
A5, however there have been no allergic reactions reported in all volunteers
exposed to Annexin A5. 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
Male
age between 18-50 yrs
signed informed consent
Exclusion criteria
-Cardiovascular disease
-Hypertension (systole > 140 mmHg, diastole > 90 mmHg)
-Hypercholesterolemia (fasting total cholesterol > 6,0 mmol/l)
-Drug abuse
-Concomittant medication use
-Inability to perform the ischemic isometric muscle contraction
-Diabetes Mellitus (fasting glucose > 7.0 mmol/L or random glucose > 11.0 mmol/L)
-Alanine-Amino-Transferase (ALAT) >90U/L (more than twice the upper level of the normal
range)
-Creatinine Kinase (CK) >340U/L (more than twice the upper level of the normal range)
-Participation in any trial concerning medicinal products
during the last 60 days prior to this study.
-Participation in clinical trial involving administration of radioactivity more than 5mSv, during the 5 years prior to this study.
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 | EUCTR2007-000151-33-NL |
| CCMO | NL16118.091.07 |