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

April 27, 2010 updated by: Radboud University Medical Center

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

48

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: rosuvastatin 3days
8 Subjects will use rosuvastatin 20 mg/day for 3 days
Drug: rosuvastatin
rosuvastatin 20 mg/day for 3 days.
Other Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • lipitor
PLACEBO_COMPARATOR: placebo 7 days
8 Subjects will use placebo for 7 days.
Drug: placebo 7 days
placebo 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Difference in flow mediated dilation before and after 15 minutes ischemia
Time Frame: 30 minutes
30 minutes

Secondary Outcome Measures

Outcome Measure
Time Frame
Ecto-5'-nucleotidase activity and lipid profile after statin therapy
Time Frame: 3-7 days
3-7 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radboud University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2009

Primary Completion (ACTUAL)

February 1, 2010

Study Completion (ACTUAL)

March 1, 2010

Study Registration Dates

First Submitted

September 30, 2009

First Submitted That Met QC Criteria

September 30, 2009

First Posted (ESTIMATE)

October 1, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

April 28, 2010

Last Update Submitted That Met QC Criteria

April 27, 2010

Last Verified

April 1, 2001

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FMD01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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