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

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT00441597
First received: February 28, 2007
Last updated: March 16, 2009
Last verified: March 2009
  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 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Does Atorvastatin Reduce Ischemia-Reperfusion Injury in Humans in-Vivo?

Resource links provided by NLM:


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
Study Completion Date: March 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
first 3 day treatment placebo and 4 weeks later three day treatment with atorvastatin 80 mg
Drug: atorvastatin
atorvastatine 80mg, during 3 days
Other Name: lipitor
Active Comparator: 2
first 3 day treatment atorvastatin 80 mg and 4 weeks later three day treatment with placebo
Drug: atorvastatin
atorvastatine 80mg, during 3 days
Other Name: lipitor
No Intervention: 3
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
Netherlands
Radboud University Nijmegen Medical Centre
Nijmegen, Netherlands, 6500 HB
Sponsors and Collaborators
Radboud University
Pfizer
Investigators
Principal Investigator: Gerard Rongen, MD PhD RUMCN
  More Information

Publications:
Responsible Party: G Rongen, dept Pharmacology Toxicology UMCN
ClinicalTrials.gov Identifier: NCT00441597     History of Changes
Other Study ID Numbers: atorv01
Study First Received: February 28, 2007
Last Updated: March 16, 2009
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

Additional relevant MeSH terms:
Ischemia
Cardiovascular Diseases
Reperfusion Injury
Pathologic Processes
Vascular Diseases
Postoperative Complications
Atorvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014