Cholesterol and Pharmacogenetic Study

NCT ID: NCT00451828

Last Updated: 2011-10-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

1000 participants

Study Classification

INTERVENTIONAL

Study Start Date

2002-03-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Hyperlipidemia Hypercholesterolemia Coronary Heart Disease Cardiovascular Disease

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Interventions

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Simvastatin

40mg/day

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

San Francisco General Hospital

OTHER

Sponsor Role collaborator

University of California, Los Angeles

OTHER

Sponsor Role collaborator

Cedars-Sinai Medical Center

OTHER

Sponsor Role collaborator

University of Washington

OTHER

Sponsor Role collaborator

Duke University

OTHER

Sponsor Role collaborator

UCSF Benioff Children's Hospital Oakland

OTHER

Sponsor Role lead

Responsible Party

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Children's Hospital Oakland Research Institute

Principal Investigators

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Ronald M Krauss, M.D.

Role: PRINCIPAL_INVESTIGATOR

UCSF Benioff Children's Hospital Oakland

Locations

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San Francisco General Hospital

San Francisco, California, United States

Site Status

Countries

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United States

References

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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. doi: 10.1016/j.amjcard.2005.09.134. Epub 2006 Jan 27.

Reference Type BACKGROUND
PMID: 16516587 (View on PubMed)

Theusch E, Ting FY, Qin Y, Stevens K, Naidoo D, King SM, Yang NV, Orr J, Han BY, Cyster JG, Chen YI, Rotter JI, Krauss RM, Medina MW. Participant-derived cell line transcriptomic analyses and mouse studies reveal a role for ZNF335 in plasma cholesterol statin response. Genome Med. 2024 Jul 26;16(1):93. doi: 10.1186/s13073-024-01366-9.

Reference Type DERIVED
PMID: 39061094 (View on PubMed)

Theusch E, Ting FY, Qin Y, Stevens K, Naidoo D, King SM, Yang N, Orr J, Han BY, Cyster JG, Chen YI, Rotter JI, Krauss RM, Medina MW. Participant-derived cell line transcriptomic analyses and mouse studies reveal a role for ZNF335 in plasma cholesterol statin response. bioRxiv [Preprint]. 2023 Jun 15:2023.06.14.544860. doi: 10.1101/2023.06.14.544860.

Reference Type DERIVED
PMID: 37397985 (View on PubMed)

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.

Reference Type DERIVED
PMID: 22808006 (View on PubMed)

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.

Reference Type DERIVED
PMID: 20413733 (View on PubMed)

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.

Reference Type DERIVED
PMID: 20339536 (View on PubMed)

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.

Reference Type DERIVED
PMID: 18559695 (View on PubMed)

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.

Reference Type DERIVED
PMID: 18332269 (View on PubMed)

Other Identifiers

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MM2277

Identifier Type: -

Identifier Source: org_study_id