Does Atorvastatin Reduce Ischemia-Reperfusion Injury in Humans in-Vivo?
Primary Purpose
Ischemia Reperfusion Injury, Cardiovascular Disease
Status
Completed
Phase
Phase 4
Locations
Netherlands
Study Type
Interventional
Intervention
atorvastatin
Sponsored by
About this trial
This is an interventional treatment trial for Ischemia Reperfusion Injury focused on measuring ischemia reperfusion injury, atorvastatine, preconditioning, cardiovascular disease
Eligibility 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
Sites / Locations
- Radboud University Nijmegen Medical Centre
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
No Intervention
Arm Label
1
2
3
Arm Description
first 3 day treatment placebo and 4 weeks later three day treatment with atorvastatin 80 mg
first 3 day treatment atorvastatin 80 mg and 4 weeks later three day treatment with placebo
3 days treatment with placebo twice
Outcomes
Primary Outcome Measures
Annexin A 5 targeting in the non dominant thenar muscle after ischemic exercise, as a indicator for ischemia reperfusion injury.
Secondary Outcome Measures
workload during ischemic exercise
effect of 3-day treatment with atorvastatin 80mg daily on serum lipid levels
Full Information
NCT ID
NCT00441597
First Posted
February 28, 2007
Last Updated
March 16, 2009
Sponsor
Radboud University Medical Center
Collaborators
Pfizer
1. Study Identification
Unique Protocol Identification Number
NCT00441597
Brief Title
Does Atorvastatin Reduce Ischemia-Reperfusion Injury in Humans in-Vivo?
Official Title
Does Atorvastatin Reduce Ischemia-Reperfusion Injury in Humans in-Vivo?
Study Type
Interventional
2. Study Status
Record Verification Date
March 2009
Overall Recruitment Status
Completed
Study Start Date
February 2007 (undefined)
Primary Completion Date
February 2009 (Actual)
Study Completion Date
March 2009 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Radboud University Medical Center
Collaborators
Pfizer
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ischemia Reperfusion Injury, Cardiovascular Disease
Keywords
ischemia reperfusion injury, atorvastatine, preconditioning, cardiovascular disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Active Comparator
Arm Description
first 3 day treatment placebo and 4 weeks later three day treatment with atorvastatin 80 mg
Arm Title
2
Arm Type
Active Comparator
Arm Description
first 3 day treatment atorvastatin 80 mg and 4 weeks later three day treatment with placebo
Arm Title
3
Arm Type
No Intervention
Arm Description
3 days treatment with placebo twice
Intervention Type
Drug
Intervention Name(s)
atorvastatin
Other Intervention Name(s)
lipitor
Intervention Description
atorvastatine 80mg, during 3 days
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
workload during ischemic exercise
Time Frame
workload during 10minutes of ischemic exercise
Title
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
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gerard Rongen, MD PhD
Organizational Affiliation
RUMCN
Official's Role
Principal Investigator
Facility Information:
Facility Name
Radboud University Nijmegen Medical Centre
City
Nijmegen
ZIP/Postal Code
6500 HB
Country
Netherlands
12. IPD Sharing Statement
Citations:
PubMed Identifier
15623546
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. doi: 10.1161/01.CIR.0000151612.02223.F2. Epub 2004 Dec 27.
Results Reference
background
PubMed Identifier
15685892
Citation
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.
Results Reference
background
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Does Atorvastatin Reduce Ischemia-Reperfusion Injury in Humans in-Vivo?
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