Effect of Atorvastatin (Lipitor) on Gene Expression in People With Vascular Disease
|First Received Date ICMJE||February 17, 2006|
|Last Updated Date||December 16, 2008|
|Start Date ICMJE||February 2006|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00293748 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Effect of Atorvastatin (Lipitor) on Gene Expression in People With Vascular Disease|
|Official Title ICMJE||Dose-Response Study of Modulation of Gene Expression in Peripheral Blood Mononuclear Cells by Atorvastatin|
This study will determine if the drug Atorvastatin (Lipitor) changes the genetic material found in blood cells of people with vascular (blood vessel) disease. Vascular diseases affect the blood flow in the body and can lead to a heart attack or stroke. Information gained from this study could be used to develop a more reliable blood test that predicts the risk of heart attack or stroke.
People 21 and older who have two or more risk factors for developing vascular disease are eligible for this study. Candidates are screened with a medical history, physical examination, electrocardiogram, ultrasound of the carotid (neck) arteries, blood tests, and check of blood pressure and heart rate.
Participants are randomly assigned to one of four treatment groups. Three groups receive Lipitor in a dose of either 10, 20 or 40 milligrams; the fourth group receives a placebo. All take the study drug for 3 months. In addition, they undergo the following tests and procedures:
Study Phase I (Months 2-4)
Participants in all groups are seen once a month at the NIH Clinical Center for blood tests and monitoring of drug side effects.
Study Phase 2 (Months 5-10)
Background: Atherosclerosis and its consequences - coronary heart disease and stroke - are principal causes of mortality in developed countries. Being able to accurately predict an individual's risk of vascular disease is needed for preventive strategies and measuring the effectiveness thereof. Current risk assessment tools are imperfect at best. It is possible that information from gene expression profiling of peripheral white blood cells may add predictive information about vascular risk. We previously identified a panel of 78 genes in the peripheral blood that correlated with an individual's future risk of stroke. We hypothesize that gene expression in white blood cells will be modified by an intervention that has been shown to reduce vascular risk via anti-inflammatory mechanisms: the 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase inhibitor class of lipid lowering drugs, known as "statins". The vascular protective effects of statins appear to be due in part to immune modulation and to be dose-dependent. Statin administration has been shown to modulate gene expression in peripheral blood mononuclear cells in vitro.
Objectives: Overall: To determine if atorvastatin modulates gene expression in peripheral blood mononuclear cells in a dose dependent manner in a cohort of subjects at risk of vascular disease. Specific: To determine if: (1) Inflammatory genes are specifically and temporarily modified by atrovastatin in a dose dependent manner; (2) A previously defined panel of 78 genes is included among the genes modified by atorvastatin; and (3) Gene expression changes correlate the degree of gene expression modulation by atorvastatin with the degree of lipid lowering and other inflammatory parameters such as high sensitivity C-reactive protein.
Study Design: Dose-response randomized, blinded study of atorvastatin treatment of 120 volunteer subjects with at least two conventional vascular risk factors who are not currently taking a statin. In the first and primary phase of the study, subjects will be administered atorvastatin in a blinded fashion in one of four doses (0mg, 10mg, 20mg or 40mg) for a period of three months. Block randomization will stratify on age and risk factor status. In the second and validation phase of the study, the subjects randomized to 0mg of atorvastatin in phase 1 will receive 40mg of atorvastatin for a further 3 month period. The remaining subjects will not be randomized to study drug in phase II of the study. Lipid profiles, liver function tests and muscle enzymes will be measured prior to enrollment, and during the treatment phases of the study. Gene expression profiles in the peripheral blood will be measured using Affymetrix microarrays pre treatment and at the end of phases I and II.
Outcome measures: (1) Gene changes induced by statin treatment by dosage and over time; (2) Accuracy of vascular gene panel for defining gene expression changes induced by statin treatment; and (3) Correlations of gene expression changes with conventional vascular risk factors, changes in lipid and inflammatory markers and determination of best vascular risk prediction paradigm.
|Study Type ICMJE||Observational|
|Study Design ICMJE||Not Provided|
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Intervention ICMJE||Not Provided|
|Study Group/Cohort (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||December 2008|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
Note: A high HDL cholesterol (greater than 60 mg/dL) counts as a negative risk factor: its presence removes one risk factor from the total counts.
|Ages||21 Years and older|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT00293748|
|Other Study ID Numbers ICMJE||060097, 06-N-0097|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Institute of Neurological Disorders and Stroke (NINDS)|
|Collaborators ICMJE||Not Provided|
|Investigators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||December 2008|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP