Phytosterols, Ezetimibe, and Cholesterol Metabolism

Hypercholesterolemia Clinical Trial

— Phyteaux-III  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00863265
• Other study ID #: CANUSU-phyto3
• Secondary ID: R01HL050420
• Status: Completed
• Phase: Early Phase 1
• Start date: June 2009
• Est. completion date: February 2010

Study information

• Verified date: May 2018
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 in an additive fashion. In a randomized, placebo-controlled crossover trial the effects of placebo, ezetimibe treatment and ezetimibe plus phytosterol treatment will be measured.

Description:

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 separated by 7-day washout periods. Treatments will be given in random order During period B placebo phytosterols and placebo ezetimibe will be given; during period C placebo phytosterols and active ezetimibe will be given; during period A active phytosterols and active ezetimibe will be given. Study endpoints are fecal cholesterol excretion and percent cholesterol absorption determined by gas chromatography/mass spectrometry and circulating LDL cholesterol.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: February 2010
• Est. primary completion date: October 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Coronary Heart Disease
• Heart Diseases
• Hypercholesterolemia
• Myocardial Ischemia

Intervention

Drug:
• Ezetimibe
Subjects will undergo three diet periods of 21 days each separated by 7 day washouts. Food will be supplied by a metabolic kitchen and will consist of a phytosterol-deficient baseline diet. During each period subjects will receive either phytosterol esters or placebo and ezetimibe or placebo.

Other:
• Phytosterols + ezetimibe
Subjects will undergo three diet periods of 21 days each separated by 7 day washouts. Food will be supplied by a metabolic kitchen and will consist of a phytosterol-deficient baseline diet. During each period subjects will receive either phytosterol esters or placebo and ezetimibe or placebo.
• Placebo

Locations

Country	Name	City	State
United States	Center for Advance Nutrition at Utah State University	Logan	Utah

Sponsors (3)

Lead Sponsor	Collaborator
Washington University School of Medicine	National Heart, Lung, and Blood Institute (NHLBI), Utah State University

Country where clinical trial is conducted

United States, 

References & Publications (1)

Lin X, Racette SB, Lefevre M, Ma L, Spearie CA, Steger-May K, Ostlund RE Jr. Combined effects of ezetimibe and phytosterols on cholesterol metabolism: a randomized, controlled feeding study in humans. Circulation. 2011 Aug 2;124(5):596-601. doi: 10.1161/C — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cholesterol Excretion	Milligrams of fecal cholesterol and cholesterol metabolites excreted per day	At the end of week 3 on each diet
Primary	Percent Cholesterol Absorption	Percent of intestinal cholesterol absorbed. Intestinal cholesterol is comprised of dietary cholesterol intake and endogenous cholesterol secreted into the intestinal lumen. Cholesterol absorption is the percent of intestinal cholesterol that is taken back up into the body and excluded from fecal excretion. It is also referred to as the efficiency of intestinal cholesterol absorption.	Determined on the final 5 days of each dietary period
Primary	LDL Cholesterol		At the end of week 3 on each diet