Short Term Statin Treatment and Endothelial Dysfunction Due to Ischemia and Reperfusion Injury
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|ClinicalTrials.gov Identifier: NCT00987974|
Recruitment Status : Completed
First Posted : October 1, 2009
Last Update Posted : April 28, 2010
Apart from their cholesterol lowering effects, statins have cholesterol‐independent pleiotropic actions, such as upregulation of 5'‐ectonucleotidase and up‐regulation of NO‐synthase that may increase tolerance against ischemia‐reperfusion injury (IR‐injury). Several animal studies have shown reduction of IR‐injury as a result of statin treatment in both the heart and the kidney. Recently the investigators have shown, using Annexin A5 targeting after voluntary ischemic exercise to assess IR‐injury, a protective effect of a 7 day oral rosuvastatin treatment. A three day treatment with atorvastatin however failed to reduce annexin targeting.
Assessment of the flow mediated dilation of the brachial artery as measure of endothelial (dys)function, is a validated model to research effects of possible protective strategies and perform mechanistic experiments on IR‐injury in humans in vivo.
The investigators hypothesize that pretreatment with statins can increase endothelial tolerance against ischemia and reperfusion injury.
To study the protective effect of pretreatment (both 3 day and 7 day) with rosuvastatin and atorvastatin on flow mediated dilation after 15 minutes ischemia and 15 minutes reperfusion.
Study design: placebo‐controlled randomised double‐blind trial
Study population: Healthy volunteers, age 18‐50
Intervention: Treatment with either rosuvastatin 20 mg, atorvastatin 80mg or placebo during either 3 or 7 days
Main study parameters: Difference in flow mediated dilation before and after 15 minutes ischemia.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Treatment with rosuvastatin or atorvastatin is not expected to harm the volunteers. Most reported side effects of rosuvastatin and atorvastatin are gastro‐intestinal complains and myalgia. The volunteers will not benefit directly from participating in this study.
|Condition or disease||Intervention/treatment||Phase|
|Ischemia Reperfusion Injury Endothelial Dysfunction||Drug: rosuvastatin Drug: atorvastatin 3 days Drug: placebo Drug: rosuvastatin 7 days Drug: atorvastatin 7 days Drug: placebo 7 days||Phase 4|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||48 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Short Term Statin Treatment and Endothelial Dysfunction Due to Ischemia and Reperfusion Injury|
|Study Start Date :||September 2009|
|Actual Primary Completion Date :||February 2010|
|Actual Study Completion Date :||March 2010|
Experimental: rosuvastatin 3days
8 Subjects will use rosuvastatin 20 mg/day for 3 days
rosuvastatin 20 mg/day for 3 days.
Other Name: crestor
Active Comparator: atorvastatin 3 days
8 Subjects will use atorvastatin 80 mg/day for 3 days.pj
Drug: atorvastatin 3 days
atorvastatin 80 mg/day for 3 days.
Other Name: lipitor
Placebo Comparator: placebo 3days
8 Subjects will use placebo for 3 days.
placebo for 3 days.
Experimental: rosuvastatin 7 days
8 Subjects will use rosuvastatin 20 mg/day for 7 days.
Drug: rosuvastatin 7 days
rosuvastatin 20 mg/day for 7 days
Other Name: crestor
Active Comparator: atorvastatin 7 days
8 Subjects will use atorvastatin 80 mg/day for 7 days.
Drug: atorvastatin 7 days
atorvastatin 80 mg/day for 7 days.
Other Name: lipitor
Placebo Comparator: placebo 7 days
8 Subjects will use placebo for 7 days.
Drug: placebo 7 days
placebo 7 days
- Difference in flow mediated dilation before and after 15 minutes ischemia [ Time Frame: 30 minutes ]
- Ecto‐5'‐nucleotidase activity and lipid profile after statin therapy [ Time Frame: 3-7 days ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00987974
|Nijmegen, Netherlands, 6500HB|