Does Atorvastatin Reduce Ischemia-Reperfusion Injury in Humans in-Vivo?

Phase 4

Completed

• Conditions: Ischemia Reperfusion Injury; Cardiovascular Disease
• Interventions: Drug: atorvastatin

• Registration Number: NCT00441597
• Lead Sponsor: Radboud University Medical Center

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.

Study Timeline

• Study Start: 2007-02
• Study First Submitted: 2007-02-28
• Study First Submitted QC: 2007-02-28
• Study First Posted: 2007-03-01
• Primary Completion: 2009-02
• Status Verified: 2009-03
• Study Completion: 2009-03
• Last Update Submitted: 2009-03-16
• Last Update Posted: 2009-03-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 30

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
2	atorvastatin	first 3 day treatment atorvastatin 80 mg and 4 weeks later three day treatment with placebo
1	atorvastatin	first 3 day treatment placebo and 4 weeks later three day treatment with atorvastatin 80 mg

Primary Outcome Measures

Name	Time	Method
Annexin A 5 targeting in the non dominant thenar muscle after ischemic exercise, as a indicator for ischemia reperfusion injury.	60 and 240 minutes after ischemic exercise

Secondary Outcome Measures

Name	Time	Method
workload during ischemic exercise	workload during 10minutes of ischemic exercise
effect of 3-day treatment with atorvastatin 80mg daily on serum lipid levels	fasting lipid levels before and at first day after 3 day treatment with atorvastatin

Trial Locations

Locations (1)

Radboud University Nijmegen Medical Centre; 🇳🇱 Nijmegen, Netherlands