Cholesterol and Pharmacogenetic Study

Phase 4

Completed

• Conditions: Hyperlipidemia; Hypercholesterolemia; Coronary Heart Disease; Cardiovascular Disease

• Registration Number: NCT00451828
• Lead Sponsor: UCSF Benioff Children's Hospital Oakland

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.

Study Timeline

• Study Start: 2002-03
• Primary Completion: 2004-10
• Study First Submitted: 2007-03-23
• Study First Submitted QC: 2007-03-23
• Study First Posted: 2007-03-26
• Status Verified: 2011-10
• Last Update Submitted: 2011-10-04
• Last Update Posted: 2011-10-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1000

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
LDL Subfractions	-2, 0, 4, 6 weeks

Trial Locations

Locations (1)

San Francisco General Hospital; 🇺🇸 San Francisco, California, United States