NCT00451828

Brief Summary

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.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,000

participants targeted

Target at P75+ for phase_4

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2002

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2004

Completed
2.5 years until next milestone

First Submitted

Initial submission to the registry

March 23, 2007

Completed
3 days until next milestone

First Posted

Study publicly available on registry

March 26, 2007

Completed
Last Updated

October 5, 2011

Status Verified

October 1, 2011

Enrollment Period

2.6 years

First QC Date

March 23, 2007

Last Update Submit

October 4, 2011

Conditions

HyperlipidemiaHypercholesterolemiaCoronary Heart DiseaseCardiovascular Disease

Keywords

StatinsCholesterolPharmacogenetics

Outcome Measures

Primary Outcomes (5)

  • Total Cholesterol

    -2, 0, 4, 6 weeks

  • LDL Cholesterol

    -2, 0, 4, 6 weeks

  • HDL Cholesterol

    -2, 0, 4, 6 weeks

  • Triglycerides

    -2, 0, 4, 6 weeks

  • C-reactive protein

    -2, 0, 4, 6 weeks

Secondary Outcomes (6)

  • Total Cholesterol/HDL Cholesterol

    -2, 0, 4, 6 weeks

  • Apolipoprotein B

    -2, 0, 4, 6 weeks

  • Apolipoprotein AI

    -2, 0, 4, 6 weeks

  • Apolipoprotein CIII

    -2, 0, 4, 6 weeks

  • LDL Peak Particle size

    -2, 0, 4, 6 weeks

  • +1 more secondary outcomes

Interventions

SimvastatinDRUG

40mg/day

Eligibility Criteria

Age30 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

San Francisco General Hospital

San Francisco, California, 94110, United States

Location

Related Publications (8)

  • 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.

    PMID: 16516587BACKGROUND

  • 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.

    PMID: 39061094DERIVED

  • 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.

    PMID: 37397985DERIVED

  • 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.

    PMID: 22808006DERIVED

  • 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.

    PMID: 20413733DERIVED

  • 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.

    PMID: 20339536DERIVED

  • 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.

    PMID: 18559695DERIVED

  • 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.

    PMID: 18332269DERIVED

MeSH Terms

Conditions

HyperlipidemiasHypercholesterolemiaCoronary DiseaseCardiovascular Diseases

Interventions

Simvastatin

Condition Hierarchy (Ancestors)

DyslipidemiasLipid Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesMyocardial IschemiaHeart DiseasesVascular Diseases

Intervention Hierarchy (Ancestors)

LovastatinNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic Compounds

Study Officials

  • Ronald M Krauss, M.D.

    UCSF Benioff Children's Hospital Oakland

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER

Study Record Dates

First Submitted

March 23, 2007

First Posted

March 26, 2007

Study Start

March 1, 2002

Primary Completion

October 1, 2004

Last Updated

October 5, 2011

Record last verified: 2011-10

Locations

US(1)