Short Term Statin Treatment and Endothelial Dysfunction Due to Ischemia and Reperfusion Injury
Condition: Ischemia Reperfusion Injury; Endothelial Dysfunction
MeSH terms: Reperfusion Injury; Ischemia; Wounds and Injuries
Study type: Interventional
Phase: Phase 4

Summary: 
      Rationale:

      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.

      Objective:

      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.
    


Intervention name(s): rosuvastatin; atorvastatin 3 days; placebo; rosuvastatin 7 days; atorvastatin 7 days; placebo 7 days
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): rosuvastatin 20 mg/day for 3 days.; atorvastatin 80 mg/day for 3 days.; placebo for 3 days.; rosuvastatin 20 mg/day for 7 days; atorvastatin 80 mg/day for 7 days.; placebo 7 days
Other intervention name(s): crestor; lipitor; crestor; lipitor
Intervention MeSH terms: Atorvastatin; Rosuvastatin Calcium
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: ischemia reperfusion injury; endothelial dysfunction; statins; rosuvastatin; atorvastatin; placebo; ecto-5'-nucleotidase; flow mediated dilation