Does Atorvastatin Reduce Ischemia-Reperfusion Injury in Humans in-Vivo? - Full Text View

Sponsors and Collaborators:	Radboud University Pfizer
Information provided by:	Radboud University
ClinicalTrials.gov Identifier:	NCT00441597

Purpose

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

Condition	Intervention	Phase
Ischemia Reperfusion Injury Cardiovascular Disease	Drug: atorvastatin	Phase IV

MedlinePlus related topics: Exercise and Physical Fitness

Drug Information available for: Atorvastatin Atorvastatin calcium

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Pharmacodynamics Study
Official Title:	Does Atorvastatin Reduce Ischemia-Reperfusion Injury in Humans in-Vivo?

Further study details as provided by Radboud University:

Primary Outcome Measures:

Annexin A 5 targeting in the non dominant thenar muscle after ischemic exercise, as a indicator for ischemia reperfusion injury. [ Time Frame: 60 and 240 minutes after ischemic exercise ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

workload during ischemic exercise [ Time Frame: workload during 10minutes of ischemic exercise ] [ Designated as safety issue: No ]
effect of 3-day treatment with atorvastatin 80mg daily on serum lipid levels [ Time Frame: fasting lipid levels before and at first day after 3 day treatment with atorvastatin ] [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	February 2007
Estimated Study Completion Date:	December 2008
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator first 3 day treatment placebo and 4 weeks later three day treatment with atorvastatin 80 mg	Drug: atorvastatin atorvastatine 80mg, during 3 days
2: Active Comparator first 3 day treatment atorvastatin 80 mg and 4 weeks later three day treatment with placebo	Drug: atorvastatin atorvastatine 80mg, during 3 days
3: No Intervention 3 days treatment with placebo twice

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

Ages Eligible for Study:	18 Years to 50 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00441597

Contacts

Contact: Stijn Wouters, MD	+31 24 361 6723	c.wouters@cardio.umcn.nl
Contact: Gerard Rongen, MD PhD	+31 24 361 3690	g.rongen@pharmtox.umcn.nl

Locations

Netherlands
Radboud University Nijmegen Medical Centre	Recruiting
Nijmegen, Netherlands, 6500 HB
Principal Investigator: Stijn Wouters, MD

Sponsors and Collaborators

Radboud University

Pfizer

Investigators

Principal Investigator:

Gerard Rongen, MD PhD

RUMCN

More Information

Publications:

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.

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.

Responsible Party:	dept Pharmacology Toxicology UMCN ( G Rongen )
Study ID Numbers:	atorv01
Study First Received:	February 28, 2007
Last Updated:	October 6, 2008
ClinicalTrials.gov Identifier:	NCT00441597
Health Authority:	Netherlands: Medical Ethics Review Committee (METC); Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:

ischemia reperfusion injury
atorvastatine
preconditioning
cardiovascular disease

Study placed in the following topic categories:

Postoperative Complications
Vascular Diseases
Ischemia
Atorvastatin
Reperfusion Injury

Additional relevant MeSH terms:

Antimetabolites
Pathologic Processes
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses
Antilipemic Agents

Enzyme Inhibitors
Cardiovascular Diseases
Anticholesteremic Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 14, 2009