Short Term Statin Treatment and Endothelial Dysfunction Due to Ischemia and Reperfusion Injury
- Conditions
- Ischemia Reperfusion InjuryEndothelial Dysfunction
- Interventions
- Drug: placeboDrug: placebo 7 days
- Registration Number
- NCT00987974
- Lead Sponsor
- Radboud University Medical Center
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 48
- Age 18-50
- Written informed consent
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Smoking
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History of any cardiovascular disease
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Hypertension (in supine position: systole >140 mmHg, diastole >90 mmHg)
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Diabetes Mellitus (fasting glucose >7.0 mmol/L or random glucose >11.0 mmol/L)
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Hyperlipidaemia (fasting total cholesterol >5.5 mmol/L or random cholesterol >6.5 mmol/L)
-
Alanine amino transferase >90 U/L
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Creatine kinase >440 U/L
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Raised rhabdomyolysis risk
- GFR <60 ml/min
- Overt clinical signs of hypothyroidism
- Myopathy in family history
- Alcohol abuse
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Concomitant chronic use of medication
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Participation to any drug-investigation during the previous 60 days as checked with VIP check.
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Professional athletes
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description rosuvastatin 3days rosuvastatin 8 Subjects will use rosuvastatin 20 mg/day for 3 days atorvastatin 3 days atorvastatin 3 days 8 Subjects will use atorvastatin 80 mg/day for 3 days.pj placebo 3days placebo 8 Subjects will use placebo for 3 days. rosuvastatin 7 days rosuvastatin 7 days 8 Subjects will use rosuvastatin 20 mg/day for 7 days. atorvastatin 7 days atorvastatin 7 days 8 Subjects will use atorvastatin 80 mg/day for 7 days. placebo 7 days placebo 7 days 8 Subjects will use placebo for 7 days.
- Primary Outcome Measures
Name Time Method Difference in flow mediated dilation before and after 15 minutes ischemia 30 minutes
- Secondary Outcome Measures
Name Time Method Ecto-5'-nucleotidase activity and lipid profile after statin therapy 3-7 days
Trial Locations
- Locations (1)
RUNMC
🇳🇱Nijmegen, Netherlands