Effect of Statins on Oxidative Stress and Endothelial Progenitor Cells

NCT00166036 | Completed Phase 2 Results

• 1 other identifier: 1038-2004
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Diabetes Mellitus; Metabolic Syndrome X; Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

• Change in Plasma Thiobarbituric Acid Reactive Substance (TBARS) Levels

  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.

  Baseline &12 Weeks

Secondary Outcomes (1)

• Change in Flow-mediated Dilatation (FMD)

  Baseline & 12 Weeks

Study Arms (2)

Atorvastatin 10MG

EXPERIMENTAL

Drug: Atorvastatin

Pravastatin 80mg

EXPERIMENTAL

Drug: Pravastatin

Interventions

Atorvastatin DRUG

12 Weeks of Oral Atorvastatin 10 mg therapy.

Atorvastatin 10MG

Pravastatin DRUG

12 Weeks of Oral Pravastatin 80 mg therapy.

Pravastatin 80mg

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Emory University: lead

Study Sites (1)

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• Murrow JR, Sher S, Ali S, Uphoff I, Patel R, Porkert M, Le NA, Jones D, Quyyumi AA. The differential effect of statins on oxidative stress and endothelial function: atorvastatin versus pravastatin. J Clin Lipidol. 2012 Jan-Feb;6(1):42-9. doi: 10.1016/j.jacl.2011.08.006. Epub 2011 Sep 13.

  PMID: 22264573 RESULT

MeSH Terms

Conditions

Diabetes Mellitus; Metabolic Syndrome; Hypercholesterolemia

Interventions

Atorvastatin; Pravastatin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Insulin Resistance; Hyperinsulinism; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Limitations and Caveats

Detection of changes in Oxidative stress with significance requires a much larger cohort study.

Results Point of Contact

• Title: Arshed A Quyyumi, MD
• Organization: Emory University

aquyyum@emory.edu

404 712 2741

Study Officials

• Arshed A Quyyumi, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 14, 2005
• Study Start: September 1, 2004
• Primary Completion: March 1, 2008
• Study Completion: April 1, 2009
• Last Updated: September 8, 2014
• Results First Posted: September 8, 2014

Record last verified: 2014-08

Locations

US (1)