Effect of Statins on Oxidative Stress and Endothelial Progenitor Cells (STOPCAP)
|Diabetes Mellitus Metabolic Syndrome X Hypercholesterolemia||Drug: Atorvastatin Drug: Pravastatin||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Effect of Statins on Oxidative Stress and Endothelial Progenitor Cells: Comparison of Atorvastatin With Pravastatin|
- Change in Plasma Thiobarbituric Acid Reactive Substance (TBARS) Levels [ Time Frame: Baseline &12 Weeks ]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.
- Change in Flow-mediated Dilatation (FMD) [ Time Frame: Baseline & 12 Weeks ]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.
|Study Start Date:||September 2004|
|Study Completion Date:||April 2009|
|Primary Completion Date:||March 2008 (Final data collection date for primary outcome measure)|
|Experimental: Atorvastatin 10MG||
12 Weeks of Oral Atorvastatin 10 mg therapy.
|Experimental: Pravastatin 80mg||
12 Weeks of Oral Pravastatin 80 mg therapy.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00166036
|United States, Georgia|
|Emory University Hospital|
|Atlanta, Georgia, United States, 30322|
|Principal Investigator:||Arshed A Quyyumi, MD||Emory University|