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HyperlipidemiaPhase 4CAPNCT00451828

Cholesterol and Pharmacogenetic Study

A Phase 4 study testing Simvastatin in people with Hyperlipidemia and Hypercholesterolemia, run by UCSF Benioff Children's Hospital Oakland at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 30 years and olderHealthy volunteers can take part
What is being tested?
Simvastatin
How many people
1,000 participants
Where
1 siteUnited States
Study dates
Mar 2002to Oct 2004
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 30 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 13Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • San Francisco General Hospital

    San Francisco, California, 94110

Other trials in United States

About this study

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.

Read the 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.

Being tested
Simvastatin
Keywords
Statins, Cholesterol, Pharmacogenetics
Medical subject headings
Hyperlipidemias, Hypercholesterolemia, Coronary Disease, Cardiovascular Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Total Cholesterol

    Measured: -2, 0, 4, 6 weeks

  2. LDL Cholesterol

    Measured: -2, 0, 4, 6 weeks

  3. HDL Cholesterol

    Measured: -2, 0, 4, 6 weeks

  4. Triglycerides

    Measured: -2, 0, 4, 6 weeks

  5. C-reactive protein

    Measured: -2, 0, 4, 6 weeks

Secondary outcomes (6)

  1. Total Cholesterol/HDL Cholesterol

    Measured: -2, 0, 4, 6 weeks

  2. Apolipoprotein B

    Measured: -2, 0, 4, 6 weeks

  3. Apolipoprotein AI

    Measured: -2, 0, 4, 6 weeks

  4. Apolipoprotein CIII

    Measured: -2, 0, 4, 6 weeks

  5. LDL Peak Particle size

    Measured: -2, 0, 4, 6 weeks

  6. LDL Subfractions

    Measured: -2, 0, 4, 6 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Mar 2007 (estimated)
  2. Study startMar 2002
  3. Primary completionOct 2004

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Prevention
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
1,000 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00451828
Sponsor's protocol ID
MM2277
Acronym
CAP
Status last verified
Oct 2011
First submitted
23 Mar 2007
Last updated
5 Oct 2011
Results posted
No
Data monitoring committee
Yes

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

    PubMed 16516587

  • 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.

    PubMed 39061094

  • 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.

    PubMed 37397985

  • 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.

    PubMed 22808006

  • 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.

    PubMed 20413733

  • 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.

    PubMed 20339536

  • 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.

    PubMed 18559695

  • 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.

    PubMed 18332269

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Simvastatin in people with Hyperlipidemia and Hypercholesterolemia, run by UCSF Benioff Children's Hospital Oakland at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Oct 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Total Cholesterol (time frame: -2, 0, 4, 6 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00451828, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2011.

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