Phytosterols, Ezetimibe, and Cholesterol Metabolism

Condition(s) targeted: Hypercholesterolemia; Coronary Heart Disease

Intervention: Phytosterol-Deficient Diet, Ezetimibe 10 mg, Phytosterol Esters Containing 2000 mg Phytosterols (Drug)

Phase: N/A

Status: Not yet recruiting

Sponsored by: Washington University School of Medicine

Official(s) and/or principal investigator(s):
Richard Ostlund, M.D., Principal Investigator, Affiliation: Washington University School of Medicine

Overall contact:
Richard Ostlund, M.D., Phone: 314-362-7617, Email: rostlund@dom.wustl.edu

Phytosterols and ezetimibe each reduce intestinal cholesterol absorption by 30-55% but appear to have different mechanisms of action. The investigators hypothesis is that phytosterols and ezetimibe given together will block cholesterol absorption nearly completely. The investigators will perform a randomized, placebo-controlled crossover feeding study in 25 subjects with greater than ideal levels of LDL cholesterol who do not require anti-cholesterol drug treatment. Subjects will consume a baseline diet provided by a feeding center that is deficient in phytosterols for three periods of 21 days in random order. During period I placebo phytosterols and placebo ezetimibe will be given; during period II placebo phytosterols and active ezetimibe will be given; during period III active phytosterols and active ezetimibe will be given. Study endpoints are fecal cholesterol excretion and percent cholesterol absorption determined by gas chromatography/mass spectrometry, circulating phytosterol levels and circulating LDL cholesterol levels.

Official title: Regulation of Cholesterol Absorption: LDL Cholesterol Response to a Combination of Phytosterols and Ezetimibe (Phyto-3)

Study design: Basic Science, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Efficacy Study

Primary outcome: Cholesterol Absorption and Excretion

Secondary outcome: LDL cholesterol

Minimum age: 18 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Male or female of any race or ethnicity between 18 to 80 years of age;

- Body mass index between 20 - 35 kg/m2;

- LDL-cholesterol between 130 - 189 mg/dL based on the average of duplicate screening

measures. If the two LDL-C levels differ by more than 30 mg/dL, a third test will be scheduled with all three results averaged;

- Free of chronic disease;

- Willing to eat only the foods that are provided by the Center during the diet

periods;

- Willing to abstain from the consumption of alcohol for 48-hours prior to blood draw

days;

- Willing to drink no more than 5 cups of caffeine-containing beverages a day.

Exclusion Criteria:

- Age < 18 or > 80 years;

- Based on duplicate screening laboratory values: 1)LDL-C >=190 mg/dL; 2)TG >=250

mg/dL;3)blood pressure >= 160 mm Hg systolic or 95 mm Hg diastolic;

- Documented presence of atherosclerotic disease;

- Diabetes mellitus;

- Renal, hepatic, endocrine, gastrointestinal, hematological or other systemic disease;

- Body mass index > 35;

- For women, pregnancy, breast feeding or postpartum < 6 months;

- For women, peri-menopausal;

- For women, sexually active but not practicing effective birth control methods;

- History of drug or alcohol abuse;

- History of depression or mental illness requiring treatment or medication within the

last 6 months;

- multiple food allergies or significant food preferences or restrictions that would

interfere with diet adherence;

- Chronic use of over-the-counter medication which would interfere with study endpoints

including laxatives and antacids;

- Lifestyle or schedule incompatible with the study protocol;

- Planned continued use of dietary supplements through the study trial;

- Taking any lipid-lowering, or other medications known to affect blood cholesterol.

Richard Ostlund, M.D., Phone: 314-362-7617, Email: rostlund@dom.wustl.edu

Center for Advance Nutrition at Utah State University, Logan, Utah 84322-4715, United States

Starting date: April 2009
Last updated: March 16, 2009