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Phytosterols, Ezetimibe, and Cholesterol Metabolism (Phyteaux-III)

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ClinicalTrials.gov Identifier: NCT00863265
Recruitment Status : Completed
First Posted : March 17, 2009
Results First Posted : June 1, 2018
Last Update Posted : June 1, 2018
Sponsor:
Collaborators:
Utah State University
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Washington University School of Medicine

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.

Condition or disease Intervention/treatment Phase
Hypercholesterolemia Coronary Heart Disease Drug: Ezetimibe Other: Phytosterols + ezetimibe Other: Placebo Early Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
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.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Phytosterols solutions were provided as food oil only (placebo) or food oil containing 2000 mg/day phytosterols (Phytosterols). Active and placebo ezetimibe tablets were provided by Merck.
Primary Purpose: Basic Science
Official Title: Regulation of Cholesterol Absorption: LDL Cholesterol Response to a Combination of Phytosterols and Ezetimibe (Phyto-3)
Study Start Date : June 2009
Actual Primary Completion Date : October 2009
Actual Study Completion Date : February 2010

Resource links provided by the National Library of Medicine

Drug Information available for: Ezetimibe

Arm Intervention/treatment
Experimental: Crossover order ABC
The order of treatments is A (phytosterols + ezetimibe), B (double placebo), and C (active ezetimibe and phytosterol placebo).
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 Name: C

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.
Other Name: A

Other: Placebo
Other Name: B

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

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.
Other Name: A

Other: Placebo
Other Name: B

Experimental: Crossover order BAC
The order of treatments is B (double placebo), A (phytosterols + ezetimibe), and C (active ezetimibe and phytosterol placebo)
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 Name: C

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.
Other Name: A

Other: Placebo
Other Name: B

Experimental: Crossover order ACB
The order of treatments is A (phytosterols + ezetimibe), C (active ezetimibe and placebo phytosterols, and B (double placebo).
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 Name: C

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.
Other Name: A

Other: Placebo
Other Name: B

Experimental: Crossover order CAB
The order of treatments is C (active ezetimibe and placebo phytosterols), A (phytosterols + ezetimibe), and B (double placebo).
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 Name: C

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.
Other Name: A

Other: Placebo
Other Name: B

Experimental: Crossover order CBA
The order of treatments is C (active ezetimibe and placebo phytosterols), B (double placebo), and A (phytosterols and ezetimibe).
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 Name: C

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.
Other Name: A

Other: Placebo
Other Name: B




Primary Outcome Measures :
  1. Cholesterol Excretion [ Time Frame: At the end of week 3 on each diet ]
    Milligrams of fecal cholesterol and cholesterol metabolites excreted per day

  2. Percent Cholesterol Absorption [ Time Frame: Determined on the final 5 days of each dietary period ]
    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.

  3. LDL Cholesterol [ Time Frame: At the end of week 3 on each diet ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00863265


Locations
United States, Utah
Center for Advance Nutrition at Utah State University
Logan, Utah, United States, 84322-4715
Sponsors and Collaborators
Washington University School of Medicine
Utah State University
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Richard Ostlund, M.D. Washington University School of Medicine

Publications of Results:
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00863265     History of Changes
Other Study ID Numbers: CANUSU-phyto3
R01HL050420 ( U.S. NIH Grant/Contract )
First Posted: March 17, 2009    Key Record Dates
Results First Posted: June 1, 2018
Last Update Posted: June 1, 2018
Last Verified: May 2018

Keywords provided by Washington University School of Medicine:
Phytosterols
Ezetimibe
Cholesterol Excretion
Cholesterol Absorption
Diet
Mass Spectrometry
Deuterium

Additional relevant MeSH terms:
Heart Diseases
Hypercholesterolemia
Coronary Disease
Coronary Artery Disease
Myocardial Ischemia
Cardiovascular Diseases
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Vascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Ezetimibe
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents