Clinical trial NCT00441597: Does Atorvastatin Reduce Ischemia-Reperfusion Injury in Humans in-Vivo?
Official title: Does Atorvastatin Reduce Ischemia-Reperfusion Injury in Humans in-Vivo?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Ischemia Reperfusion Injury
Cardiovascular Disease
Keywords: ischemia reperfusion injury
atorvastatine
preconditioning
cardiovascular disease
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2007-03-01
Enrollment: 30
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: To study the impact of 3 day exposure to atorvastatin 80mg on Annexin A5 targeting after ischemic exercise in the non-dominant forearm.

Detailed description: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (also known as statins) have been found to reduce cardiovascular events. This protective effect has been traditionally explained by lowering plasma cholesterol and subsequent reduced progression of atherosclerosis. However in animal experiments statins have also shown the ability to induce pharmacologic preconditioning and thereby reduce infarct size. This effect contributes to the beneficial effect of statins on reducing of cardiovascular events. In order to differentiate between these two mechanisms of protection we will study the effect of atorvastatin on ischemia reperfusion damage after a short exposure to atorvastatin, before the lipid lowering effect of atorvastatin becomes apparent.

Eligibility criteria: Inclusion Criteria:

* Male
* Age 18-50 years
* Informed consent
* Physical able to perform ischemic exercise

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)
* Hyperlipidaemia (fasting total cholesterol \> 5.5 mmol/l)
* Alanine-Amino-Transferase (ALAT) \>90 U/L
* Creatinine Kinase (CK) \>440 U/L
* Drug or alcohol abuse
* Concommitant chronic use of medication
* Administration of radioactivity in research setting during the last 5 years
* Participation to any drug-investigation during the previous 60 days as checked with VIP check according to CRCN standard procedures

Primary outcomes:
measure: Annexin A 5 targeting in the non dominant thenar muscle after ischemic exercise, as a indicator for ischemia reperfusion injury.
timeFrame: 60 and 240 minutes after ischemic exercise
Secondary outcomes:
measure: workload during ischemic exercise
timeFrame: workload during 10minutes of ischemic exercise
measure: effect of 3-day treatment with atorvastatin 80mg daily on serum lipid levels
timeFrame: fasting lipid levels before and at first day after 3 day treatment with atorvastatin
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Centre
Study officials:
affiliation: RUMCN
name: Gerard Rongen, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rongen GA, Oyen WJ, Ramakers BP, Riksen NP, Boerman OC, Steinmetz N, Smits P. Annexin A5 scintigraphy of forearm as a novel in vivo model of skeletal muscle preconditioning in humans. Circulation. 2005 Jan 18;111(2):173-8. doi: 10.1161/01.CIR.0000151612.02223.F2. Epub 2004 Dec 27.
citation: Riksen NP, Smits P, Rongen GA. Ischaemic preconditioning: from molecular characterisation to clinical application--part II. Neth J Med. 2004 Dec;62(11):409-23.