Clinical trial NCT00863265: Phytosterols, Ezetimibe, and Cholesterol Metabolism
Official title: Regulation of Cholesterol Absorption: LDL Cholesterol Response to a Combination of Phytosterols and Ezetimibe (Phyto-3)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Hypercholesterolemia
Coronary Heart Disease
Keywords: Phytosterols
Ezetimibe
Cholesterol Excretion
Cholesterol Absorption
Diet
Mass Spectrometry
Deuterium
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Utah State University
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2009-03-17
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This is a randomized, crossover design. There are three periods of 21 days separated by two 7 day washouts. All subjects eat a controlled low-phytosterol diet for each of the three periods. During period B placebo phytosterols and placebo ezetimibe are given. During period C phytosterol placebo and active ezetimibe are given. During period A active phytosterols and active ezetimibe are given. Periods are assigned in random order as described in Arms below.
Primary purpose: BASIC_SCIENCE

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.

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.

Primary outcomes:
measure: Cholesterol Excretion
timeFrame: At the end of week 3 on each diet
measure: Percent Cholesterol Absorption
timeFrame: Determined on the final 5 days of each dietary period
measure: LDL Cholesterol
timeFrame: At the end of week 3 on each diet
Secondary outcomes:
Other outcomes:
Locations:
city: Logan
country: United States
facility: Center for Advance Nutrition at Utah State University
state: Utah
Study officials:
affiliation: Washington University School of Medicine
name: Richard Ostlund, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.