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

Cardiovascular Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00441597
• Other study ID #: atorv01
• Status: Completed
• Phase: Phase 4
• First received: February 28, 2007
• Last updated: March 16, 2009
• Start date: February 2007
• Est. completion date: March 2009

Study information

• Verified date: March 2009
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: March 2009
• Est. primary completion date: February 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 50 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases
• Ischemia
• Ischemia Reperfusion Injury
• Reperfusion Injury

Intervention

Drug:
• atorvastatin
atorvastatine 80mg, during 3 days

Locations

Country	Name	City	State
Netherlands	Radboud University Nijmegen Medical Centre	Nijmegen

Sponsors (2)

Lead Sponsor	Collaborator
Radboud University	Pfizer

Country where clinical trial is conducted

Netherlands, 

References & Publications (2)

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. Review. — View 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. Epub 2004 Dec 27. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	workload during ischemic exercise		workload during 10minutes of ischemic exercise	No
Secondary	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	No