Cholesterol and Pharmacogenetic Study - Full Text View

Sponsors and Collaborators:	Children's Hospital & Research Center Oakland National Heart, Lung, and Blood Institute (NHLBI) San Francisco General Hospital University of California, Los Angeles Cedars-Sinai Medical Center University of Washington Duke University
Information provided by:	Children's Hospital & Research Center Oakland
ClinicalTrials.gov Identifier:	NCT00451828

Purpose

The overall objective of the CAP study was to determine genetic influences on efficacy of simvastatin treatment with regard to LDL cholesterol reduction and changes in other markers of cardiovascular disease risk.

Condition	Intervention	Phase
Hyperlipidemia Hypercholesterolemia Coronary Heart Disease Cardiovascular Disease	Drug: Simvastatin	Phase IV

Genetics Home Reference related topics: hypercholesterolemia

MedlinePlus related topics: Cholesterol Coronary Artery Disease Heart Diseases

Drug Information available for: Cholest-5-en-3-ol (3beta)- Simvastatin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study
Official Title:	Cholesterol and Pharmacogenetic Study

Further study details as provided by Children's Hospital & Research Center Oakland:

Primary Outcome Measures:

Total Cholesterol [ Time Frame: -2, 0, 4, 6 weeks ] [ Designated as safety issue: No ]
LDL Cholesterol [ Time Frame: -2, 0, 4, 6 weeks ] [ Designated as safety issue: No ]
HDL Cholesterol [ Time Frame: -2, 0, 4, 6 weeks ] [ Designated as safety issue: No ]
Triglycerides [ Time Frame: -2, 0, 4, 6 weeks ] [ Designated as safety issue: No ]
C-reactive protein [ Time Frame: -2, 0, 4, 6 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Total Cholesterol/HDL Cholesterol [ Time Frame: -2, 0, 4, 6 weeks ] [ Designated as safety issue: No ]
Apolipoprotein B [ Time Frame: -2, 0, 4, 6 weeks ] [ Designated as safety issue: No ]
Apolipoprotein AI [ Time Frame: -2, 0, 4, 6 weeks ] [ Designated as safety issue: No ]
Apolipoprotein CIII [ Time Frame: -2, 0, 4, 6 weeks ] [ Designated as safety issue: No ]
LDL Peak Particle size [ Time Frame: -2, 0, 4, 6 weeks ] [ Designated as safety issue: No ]
LDL Subfractions [ Time Frame: -2, 0, 4, 6 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	1000
Study Start Date:	March 2002
Estimated Study Completion Date:	March 2004
Primary Completion Date:	October 2004 (Final data collection date for primary outcome measure)

Intervention Details:

40mg/day

Detailed Description:

Despite widespread use of statin therapy for reducing risk of cardiovascular disease risk, there is considerable inter-individual variation in statin efficacy, and it would be desirable to identify markers that would be predictive of the magnitude of beneficial response. The effect of statin most strongly associated with improved clinical outcomes is reduction in LDL cholesterol. The CAP study was a six week non-randomized, open label study of simvastatin 40 mg/day in a group of 335 African-American and 609 Caucasian volunteer subjects. Measurements of plasma lipids and lipoproteins, as well as other markers of cardiovascular disease risk, were obtained at the screening and entry visits, and after four and six weeks of simvastatin treatment. Both baseline measurements and changes in response to simvastatin therapy are being used to test for associations with genetic polymorphisms. Significant findings are being replicated in other study cohorts.

Eligibility

Ages Eligible for Study:	30 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

at least 30 years of age
Total Cholesterol between 160 to 400 mg/dl
> 3 grandparents of African-American descent or > 3 grandparents of Caucasian descent
serum triglycerides < 400 mg/dl
fasting glucose < 126 mg/dl

Exclusion Criteria:

Use of lipid-lowering medication
Use of over-the-counter products containing sterol or stanol esters or fish oil
Recent or planned change in dietary intake or weight change of more than 4.5 kg
Use of corticosteroids, immunosuppressive drugs or drugs affecting the CYP3A4 system
Known liver disease or elevated transaminase levels
Elevated creatine phosphokinase levels > 10 times upper limits of normal
Uncontrolled blood pressure, or diabetes mellitus
Abnormal renal or thyroid function
Current alcohol or drug abuse
Major illness in the preceding three months
Pregnancy
Know intolerance to statins
Racial ancestry other than African-American or Caucasian

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00451828

Locations

United States, California
San Francisco General Hospital
San Francisco, California, United States, 94110

Sponsors and Collaborators

Children's Hospital & Research Center Oakland

National Heart, Lung, and Blood Institute (NHLBI)

San Francisco General Hospital

University of California, Los Angeles

Cedars-Sinai Medical Center

University of Washington

Duke University

Investigators

Principal Investigator:

Ronald M Krauss, M.D.

Children's Hospital & Research Center Oakland

More Information

Publications:

Simon JA, Lin F, Hulley SB, Blanche PJ, Waters D, Shiboski S, Rotter JI, Nickerson DA, Yang H, Saad M, Krauss RM. Phenotypic predictors of response to simvastatin therapy among African-Americans and Caucasians: the Cholesterol and Pharmacogenetics (CAP) Study. Am J Cardiol. 2006 Mar 15;97(6):843-50. Epub 2006 Jan 27.

Publications automatically indexed to this study:

Medina MW, Gao F, Ruan W, Rotter JI, Krauss RM. Alternative splicing of 3-hydroxy-3-methylglutaryl coenzyme A reductase is associated with plasma low-density lipoprotein cholesterol response to simvastatin. Circulation. 2008 Jul 22;118(4):355-62. Epub 2008 Jun 16.

Krauss RM, Mangravite LM, Smith JD, Medina MW, Wang D, Guo X, Rieder MJ, Simon JA, Hulley SB, Waters D, Saad M, Williams PT, Taylor KD, Yang H, Nickerson DA, Rotter JI. Variation in the 3-hydroxyl-3-methylglutaryl coenzyme a reductase gene is associated with racial differences in low-density lipoprotein cholesterol response to simvastatin treatment. Circulation. 2008 Mar 25;117(12):1537-44. Epub 2008 Mar 10.

Responsible Party:	Children's Hospital Oakland Research Institute ( Ronald M. Krauss, MD )
Study ID Numbers:	MM2277
Study First Received:	March 23, 2007
Last Updated:	February 10, 2009
ClinicalTrials.gov Identifier:	NCT00451828
Health Authority:	United States: Institutional Review Board

Keywords provided by Children's Hospital & Research Center Oakland:

Statins
Cholesterol
Pharmacogenetics

Study placed in the following topic categories:

Arterial Occlusive Diseases
Heart Diseases
Hyperlipidemias
Metabolic Diseases
Simvastatin
Myocardial Ischemia
Vascular Diseases
Ischemia

Arteriosclerosis
Coronary Disease
Metabolic disorder
Hypercholesterolemia
Coronary Artery Disease
Dyslipidemias
Lipid Metabolism Disorders

Additional relevant MeSH terms:

Antimetabolites
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses
Antilipemic Agents
Enzyme Inhibitors

Cardiovascular Diseases
Anticholesteremic Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 12, 2009