Effect of Statins on Oxidative Stress and Endothelial Progenitor Cells
Condition: Diabetes Mellitus; Metabolic Syndrome X; Hypercholesterolemia
MeSH terms: Metabolic Syndrome; Hypercholesterolemia
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

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.
    

Intervention name(s): Atorvastatin; Pravastatin
Intervention type(s): Drug; Drug
Intervention description(s): 12 Weeks of Oral Atorvastatin 10 mg therapy.; 12 Weeks of Oral Pravastatin 80 mg therapy.
Intervention MeSH terms: Atorvastatin; Pravastatin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment