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Cholesterol and Pharmacogenetic Study (CAP)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00451828
First Posted: March 26, 2007
Last Update Posted: October 5, 2011
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
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
  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 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Cholesterol and Pharmacogenetic Study

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Total Cholesterol [ Time Frame: -2, 0, 4, 6 weeks ]
  • LDL Cholesterol [ Time Frame: -2, 0, 4, 6 weeks ]
  • HDL Cholesterol [ Time Frame: -2, 0, 4, 6 weeks ]
  • Triglycerides [ Time Frame: -2, 0, 4, 6 weeks ]
  • C-reactive protein [ Time Frame: -2, 0, 4, 6 weeks ]

Secondary Outcome Measures:
  • Total Cholesterol/HDL Cholesterol [ Time Frame: -2, 0, 4, 6 weeks ]
  • Apolipoprotein B [ Time Frame: -2, 0, 4, 6 weeks ]
  • Apolipoprotein AI [ Time Frame: -2, 0, 4, 6 weeks ]
  • Apolipoprotein CIII [ Time Frame: -2, 0, 4, 6 weeks ]
  • LDL Peak Particle size [ Time Frame: -2, 0, 4, 6 weeks ]
  • LDL Subfractions [ Time Frame: -2, 0, 4, 6 weeks ]

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

Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Trupp M, Zhu H, Wikoff WR, Baillie RA, Zeng ZB, Karp PD, Fiehn O, Krauss RM, Kaddurah-Daouk R. Metabolomics reveals amino acids contribute to variation in response to simvastatin treatment. PLoS One. 2012;7(7):e38386. doi: 10.1371/journal.pone.0038386. Epub 2012 Jul 9.
Mangravite LM, Medina MW, Cui J, Pressman S, Smith JD, Rieder MJ, Guo X, Nickerson DA, Rotter JI, Krauss RM. Combined influence of LDLR and HMGCR sequence variation on lipid-lowering response to simvastatin. Arterioscler Thromb Vasc Biol. 2010 Jul;30(7):1485-92. doi: 10.1161/ATVBAHA.110.203273. Epub 2010 Apr 22.
Barber MJ, Mangravite LM, Hyde CL, Chasman DI, Smith JD, McCarty CA, Li X, Wilke RA, Rieder MJ, Williams PT, Ridker PM, Chatterjee A, Rotter JI, Nickerson DA, Stephens M, Krauss RM. Genome-wide association of lipid-lowering response to statins in combined study populations. PLoS One. 2010 Mar 22;5(3):e9763. doi: 10.1371/journal.pone.0009763.
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. doi: 10.1161/CIRCULATIONAHA.108.773267. 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. doi: 10.1161/CIRCULATIONAHA.107.708388. Epub 2008 Mar 10.

Responsible Party: Ronald M. Krauss, MD, Children's Hospital Oakland Research Institute
ClinicalTrials.gov Identifier: NCT00451828     History of Changes
Other Study ID Numbers: MM2277
First Submitted: March 23, 2007
First Posted: March 26, 2007
Last Update Posted: October 5, 2011
Last Verified: October 2011

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

Additional relevant MeSH terms:
Cardiovascular Diseases
Heart Diseases
Hypercholesterolemia
Coronary Disease
Coronary Artery Disease
Myocardial Ischemia
Hyperlipidemias
Hyperlipoproteinemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Vascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Simvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors


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