Short Term Statin Treatment and Endothelial Dysfunction Due to Ischemia and Reperfusion Injury

This study has been completed.
Sponsor:
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT00987974
First received: September 30, 2009
Last updated: April 27, 2010
Last verified: April 2001
  Purpose

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.


Condition Intervention 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
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Short Term Statin Treatment and Endothelial Dysfunction Due to Ischemia and Reperfusion Injury

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • Difference in flow mediated dilation before and after 15 minutes ischemia [ Time Frame: 30 minutes ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Ecto‐5'‐nucleotidase activity and lipid profile after statin therapy [ Time Frame: 3-7 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 48
Study Start Date: September 2009
Study Completion Date: March 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: rosuvastatin 3days
8 Subjects will use rosuvastatin 20 mg/day for 3 days
Drug: rosuvastatin
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.
Drug: placebo
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

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age 18‐50
  • Written informed consent

Exclusion Criteria:

  • Smoking
  • 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 or random cholesterol >6.5 mmol/L)
  • Alanine amino transferase >90 U/L
  • Creatine kinase >440 U/L
  • Raised rhabdomyolysis risk

    • GFR <60 ml/min
    • Overt clinical signs of hypothyroidism
    • Myopathy in family history
    • Alcohol abuse
  • Concomitant chronic use of medication
  • Participation to any drug‐investigation during the previous 60 days as checked with VIP check.
  • Professional athletes
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00987974

Locations
Netherlands
RUNMC
Nijmegen, Netherlands, 6500HB
Sponsors and Collaborators
Radboud University
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: G. Rongen, RUNMC
ClinicalTrials.gov Identifier: NCT00987974     History of Changes
Other Study ID Numbers: FMD01
Study First Received: September 30, 2009
Last Updated: April 27, 2010
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
ischemia reperfusion injury
endothelial dysfunction
statins
rosuvastatin
atorvastatin
placebo
ecto-5'-nucleotidase
flow mediated dilation

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

ClinicalTrials.gov processed this record on April 23, 2014