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Cholesterol and Pharmacogenetic Study (CAP)

Primary Purpose

Hyperlipidemia, Hypercholesterolemia, Coronary Heart Disease

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Simvastatin
Sponsored by
UCSF Benioff Children's Hospital Oakland
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional prevention trial for Hyperlipidemia focused on measuring Statins, Cholesterol, Pharmacogenetics

Eligibility Criteria

30 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • San Francisco General Hospital

Outcomes

Primary Outcome Measures

Total Cholesterol
LDL Cholesterol
HDL Cholesterol
Triglycerides
C-reactive protein

Secondary Outcome Measures

Total Cholesterol/HDL Cholesterol
Apolipoprotein B
Apolipoprotein AI
Apolipoprotein CIII
LDL Peak Particle size
LDL Subfractions

Full Information

First Posted
March 23, 2007
Last Updated
October 4, 2011
Sponsor
UCSF Benioff Children's Hospital Oakland
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
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1. Study Identification

Unique Protocol Identification Number
NCT00451828
Brief Title
Cholesterol and Pharmacogenetic Study
Acronym
CAP
Official Title
Cholesterol and Pharmacogenetic Study
Study Type
Interventional

2. Study Status

Record Verification Date
October 2011
Overall Recruitment Status
Completed
Study Start Date
March 2002 (undefined)
Primary Completion Date
October 2004 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
UCSF Benioff Children's Hospital Oakland
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

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyperlipidemia, Hypercholesterolemia, Coronary Heart Disease, Cardiovascular Disease
Keywords
Statins, Cholesterol, Pharmacogenetics

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
1000 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Simvastatin
Intervention Description
40mg/day
Primary Outcome Measure Information:
Title
Total Cholesterol
Time Frame
-2, 0, 4, 6 weeks
Title
LDL Cholesterol
Time Frame
-2, 0, 4, 6 weeks
Title
HDL Cholesterol
Time Frame
-2, 0, 4, 6 weeks
Title
Triglycerides
Time Frame
-2, 0, 4, 6 weeks
Title
C-reactive protein
Time Frame
-2, 0, 4, 6 weeks
Secondary Outcome Measure Information:
Title
Total Cholesterol/HDL Cholesterol
Time Frame
-2, 0, 4, 6 weeks
Title
Apolipoprotein B
Time Frame
-2, 0, 4, 6 weeks
Title
Apolipoprotein AI
Time Frame
-2, 0, 4, 6 weeks
Title
Apolipoprotein CIII
Time Frame
-2, 0, 4, 6 weeks
Title
LDL Peak Particle size
Time Frame
-2, 0, 4, 6 weeks
Title
LDL Subfractions
Time Frame
-2, 0, 4, 6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ronald M Krauss, M.D.
Organizational Affiliation
UCSF Benioff Children's Hospital Oakland
Official's Role
Principal Investigator
Facility Information:
Facility Name
San Francisco General Hospital
City
San Francisco
State/Province
California
ZIP/Postal Code
94110
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
16516587
Citation
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.
Results Reference
background
PubMed Identifier
22808006
Citation
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.
Results Reference
derived
PubMed Identifier
20413733
Citation
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.
Results Reference
derived
PubMed Identifier
20339536
Citation
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.
Results Reference
derived
PubMed Identifier
18559695
Citation
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.
Results Reference
derived
PubMed Identifier
18332269
Citation
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.
Results Reference
derived

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Cholesterol and Pharmacogenetic Study

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