Cholesterol and Pharmacogenetic Study
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Enrollment
- 1,000
- Locations
- 2
- Primary Endpoint
- Total Cholesterol
Study Overview
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 Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- 30 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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
Outcomes
Primary Outcomes
Total Cholesterol
Time Frame: -2, 0, 4, 6 weeks
LDL Cholesterol
Time Frame: -2, 0, 4, 6 weeks
HDL Cholesterol
Time Frame: -2, 0, 4, 6 weeks
Triglycerides
Time Frame: -2, 0, 4, 6 weeks
C-reactive protein
Time Frame: -2, 0, 4, 6 weeks
Secondary Outcomes
- 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)