Phytosterols, Ezetimibe, and Cholesterol Metabolism

NCT ID: NCT00863265

Last Updated: 2018-06-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-30
• Study Completion Date: 2010-02-28

Brief 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.

Detailed 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.

Conditions

Hypercholesterolemia; Coronary Heart Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Crossover order ABC

The order of treatments is A (phytosterols + ezetimibe), B (double placebo), and C (active ezetimibe and phytosterol placebo).

Group Type: EXPERIMENTAL

Ezetimibe

Intervention Type: DRUG

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.

Phytosterols + ezetimibe

Intervention Type: OTHER

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

Intervention Type: OTHER

Crossover order BCA

The order of treatments is B (double placebo), C (active ezetimibe and phytosterol placebo), and A (phytosterols + ezetimibe).

Group Type: EXPERIMENTAL

Ezetimibe

Intervention Type: DRUG

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.

Phytosterols + ezetimibe

Intervention Type: OTHER

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

Intervention Type: OTHER

Crossover order BAC

The order of treatments is B (double placebo), A (phytosterols + ezetimibe), and C (active ezetimibe and phytosterol placebo)

Group Type: EXPERIMENTAL

Ezetimibe

Intervention Type: DRUG

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.

Phytosterols + ezetimibe

Intervention Type: OTHER

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

Intervention Type: OTHER

Crossover order ACB

The order of treatments is A (phytosterols + ezetimibe), C (active ezetimibe and placebo phytosterols, and B (double placebo).

Group Type: EXPERIMENTAL

Ezetimibe

Intervention Type: DRUG

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.

Phytosterols + ezetimibe

Intervention Type: OTHER

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

Intervention Type: OTHER

Crossover order CAB

The order of treatments is C (active ezetimibe and placebo phytosterols), A (phytosterols + ezetimibe), and B (double placebo).

Group Type: EXPERIMENTAL

Ezetimibe

Intervention Type: DRUG

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.

Phytosterols + ezetimibe

Intervention Type: OTHER

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

Intervention Type: OTHER

Crossover order CBA

The order of treatments is C (active ezetimibe and placebo phytosterols), B (double placebo), and A (phytosterols and ezetimibe).

Group Type: EXPERIMENTAL

Ezetimibe

Intervention Type: DRUG

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.

Phytosterols + ezetimibe

Intervention Type: OTHER

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

Intervention Type: OTHER

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: OTHER

Placebo

Intervention Type: OTHER

Other Intervention Names

C; A; B

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Utah State University

OTHER

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Richard Ostlund, M.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Center for Advance Nutrition at Utah State University

Logan, Utah, United States

Countries

United States

References

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/CIRCULATIONAHA.110.006692. Epub 2011 Jul 18.

Reference Type: RESULT

PMID: 21768544 (View on PubMed)

Other Identifiers

R01HL050420

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CANUSU-phyto3

Identifier Type: -

Identifier Source: org_study_id