Cholesterol and Pharmacogenetic Study

Cardiovascular Disease Clinical Trial

— CAP  

Official title:

Cholesterol and Pharmacogenetic Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00451828
• Other study ID #: MM2277
• Status: Completed
• Phase: Phase 4
• First received: March 23, 2007
• Last updated: October 4, 2011
• Start date: March 2002

Study information

• Verified date: October 2011
• Source: Children's Hospital & Research Center Oakland
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1000
• Est. primary completion date: October 2004
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 30 Years and older

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases
• Coronary Artery Disease
• Coronary Disease
• Coronary Heart Disease
• Hypercholesterolemia
• Hyperlipidemia
• Hyperlipidemias
• Myocardial Ischemia

Intervention

Drug:
• Simvastatin
40mg/day

Locations

Country	Name	City	State
United States	San Francisco General Hospital	San Francisco	California

Sponsors (7)

Lead Sponsor	Collaborator
Children's Hospital & Research Center Oakland	Cedars-Sinai Medical Center, Duke University, National Heart, Lung, and Blood Institute (NHLBI), San Francisco General Hospital, University of California, Los Angeles, University of Washington

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. Epub 2006 Jan 27. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total Cholesterol		-2, 0, 4, 6 weeks	No
Primary	LDL Cholesterol		-2, 0, 4, 6 weeks	No
Primary	HDL Cholesterol		-2, 0, 4, 6 weeks	No
Primary	Triglycerides		-2, 0, 4, 6 weeks	No
Primary	C-reactive protein		-2, 0, 4, 6 weeks	No
Secondary	Total Cholesterol/HDL Cholesterol		-2, 0, 4, 6 weeks	No
Secondary	Apolipoprotein B		-2, 0, 4, 6 weeks	No
Secondary	Apolipoprotein AI		-2, 0, 4, 6 weeks	No
Secondary	Apolipoprotein CIII		-2, 0, 4, 6 weeks	No
Secondary	LDL Peak Particle size		-2, 0, 4, 6 weeks	No
Secondary	LDL Subfractions		-2, 0, 4, 6 weeks	No