Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Effect of Statins on Oxidative Stress and Endothelial Progenitor Cells (STOPCAP)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Arshed A. Quyyumi, Emory University
ClinicalTrials.gov Identifier:
NCT00166036
First received: September 12, 2005
Last updated: August 28, 2014
Last verified: August 2014
  Purpose

Thirty-six subjects with hyperlipidemia and metabolic syndrome and/or diabetes were randomized in a double-blind manner to either pravastatin 80 mg or atorvastatin 10 mg daily. Oxidative stress (dROMs assay that measures lipid hydroperoxides, plasma thiobarbituric acid reactive substances [TBARS], and aminothiol levels) and brachial artery flow-mediated dilation (FMD) were measured at baseline and after 12 weeks of statin therapy.


Condition Intervention Phase
Diabetes Mellitus
Metabolic Syndrome X
Hypercholesterolemia
Drug: Atorvastatin
Drug: Pravastatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Statins on Oxidative Stress and Endothelial Progenitor Cells: Comparison of Atorvastatin With Pravastatin

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Change in Plasma Thiobarbituric Acid Reactive Substance (TBARS) Levels [ Time Frame: Baseline &12 Weeks ] [ Designated as safety issue: No ]
    Oxidative stress was assessed with plasma thiobarbituric acid reactive substance (TBARS) levels (an index of lipid peroxidation).Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage.We hypothesized that equipotent doses of these two statins will have divergent effects on markers of oxidative stress and endothelial function.


Secondary Outcome Measures:
  • Change in Flow-mediated Dilatation (FMD) [ Time Frame: Baseline & 12 Weeks ] [ Designated as safety issue: No ]
    Flow-mediated dilatation (FMD) of the brachial artery was used to asses Endothelial Function. The endothelium, by releasing nitric oxide (NO), promotes vasodilation and inhibits inflammation, thrombosis, and vascular smooth muscle cell proliferation.We hypothesized that equipotent doses of these two statins will have divergent effects on markers of oxidative stress and endothelial function.


Enrollment: 36
Study Start Date: September 2004
Study Completion Date: April 2009
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Atorvastatin 10MG Drug: Atorvastatin
12 Weeks of Oral Atorvastatin 10 mg therapy.
Experimental: Pravastatin 80mg Drug: Pravastatin
12 Weeks of Oral Pravastatin 80 mg therapy.

Detailed Description:

Individuals with a high cholesterol level, diabetes or metabolic syndrome (collection of abnormalities such as high blood pressure, high triglyceride levels [fat], obesity, high blood glucose level) have an increased risk of developing a hardening of the arteries and heart disease.

A group of medications called statins, commonly used worldwide to lower cholesterol levels, are known to reduce the risk of heart disease through their effects on reducing cholesterol levels. These medications also have effects beyond the lowering of cholesterol that may help mediate their beneficial effects on the heart and blood vessels.

These include a reduced production of molecules that harm the arteries such as reactive oxygen species (ROS) and increasing the number of stem cells that help repair vessels, called endothelial progenitor cells (EPCs).

Recent studies have shown that different statins might have different effects on protecting people from developing heart disease. These differences may be due to differences in these non-cholesterol lowering processes, and are the subject of this study.

Standard of Care:

The two statins that will be used in this study, pravastatin (Pravachol ®) and atorvastatin (Lipitor®), are approved for use in people with a high cholesterol level or heart disease. These medications are generally very well tolerated with minimal side effects. They are not approved for use in patients to increase the level of EPCs or to reduce the production of ROS, and therefore are considered experimental for this indication. Currently there are no drugs that are specifically approved for these indications.

How the Problem Will be Studied:

These statins will be given to patients who have high cholesterol and either diabetes or the metabolic syndrome once a day for 12 weeks. We, the investigators at Emory, will measure the level of EPCs and ROS before and during the administration of the statin. We will also investigate how well the blood vessels dilate in response to these medications by performing an imaging study of the forearm artery using ultrasound.

The study is blinded and there is an equal chance of receiving either atorvastatin 10mg or pravastatin 80mg which are likely to lower cholesterol level by a similar amount.

How Research Will Advance Scientific Knowledge:

The goal of this study is to determine if atorvastatin will increase the number of circulating EPCs and reduce the production of ROS more than pravastatin. This may help explain the differences between these drugs that have been observed in some recently published trials.

  Eligibility

Ages Eligible for Study:   21 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males or females without child bearing potential aged 21-80 years
  • Fasting low-density lipoprotein (LDL) level > 120mg/dL.
  • Either known to be diabetic or have at least 3 components of metabolic syndrome that are defined below:

    • Hypertension defined as blood pressure (BP) > 140 systolic or > 90 mmHg diastolic, or stable medical therapy for documented hypertension;
    • Fasting glucose > 110 mg/dL;
    • Waist > 40 inches in males, and > 35 inches in females;
    • Triglycerides > 150mg/dL; or
    • High-density lipoprotein (HDL) cholesterol < 40 mg/dL in males and < 50 mg/dL in females.
  • Able to provide written informed consent
  • Non-smoker

Exclusion Criteria:

  • On any oral antioxidants or lipid lowering medications in the previous 8 weeks
  • Age < 21 or > 80 years
  • Premenopausal females with potential for pregnancy
  • LDL cholesterol level < 120 mg/dl
  • Initiation or change in dose of any concomitant medical therapy within 2 months before the study
  • Uncontrolled hypertension with BP > 180 mmHg systolic and > 120 mmHg diastolic
  • Current smoker
  • Previous intolerance or allergy to statins
  • Acute infection in previous 4 weeks
  • History of substance abuse
  • Uninterpretable Brachial Artery Reactivity Study
  • Current neoplasm
  • Chronic renal failure (creatinine > 2.5 mg/dL) or liver failure (liver enzymes > 2X normal)
  • Acute coronary syndrome, heart failure, cerebrovascular accident (CVA), or coronary intervention within 3 months
  • Known aortic stenosis, hypertrophic cardiomyopathy, or symptomatic heart failure.
  • Inability to give informed consent
  • Inability to return to Emory for follow-up
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00166036

Locations
United States, Georgia
Emory University Hospital
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: Arshed A Quyyumi, MD Emory University
  More Information

Publications:
Responsible Party: Arshed A. Quyyumi, Professor, Emory University
ClinicalTrials.gov Identifier: NCT00166036     History of Changes
Other Study ID Numbers: 1038-2004
Study First Received: September 12, 2005
Results First Received: June 8, 2012
Last Updated: August 28, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Diabetes Mellitus
Hypercholesterolemia
Metabolic Syndrome X
Dyslipidemias
Endocrine System Diseases
Glucose Metabolism Disorders
Hyperinsulinism
Hyperlipidemias
Insulin Resistance
Lipid Metabolism Disorders
Metabolic Diseases
Atorvastatin
Pravastatin
Anticholesteremic Agents
Antimetabolites
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014