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

Radboud University Medical Center

Status and phase: Completed; Phase 4

Conditions: Ischemia Reperfusion Injury; Cardiovascular Disease

Treatments: Drug: atorvastatin

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00441597

atorv01

Details and patient eligibility

About

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

Full 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.

Enrollment: 30 estimated patients

Sex: Male

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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30 participants in 3 patient groups

1

Active Comparator group

Description:

first 3 day treatment placebo and 4 weeks later three day treatment with atorvastatin 80 mg

Treatment:

Drug: atorvastatin

2

Active Comparator group

Description:

first 3 day treatment atorvastatin 80 mg and 4 weeks later three day treatment with placebo

Treatment:

Drug: atorvastatin

3

No Intervention group

Description:

3 days treatment with placebo twice