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

Primary Purpose

Hypercholesterolemia, Coronary Heart Disease

Status

Completed

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Ezetimibe

Phytosterols + ezetimibe

Placebo

About this trial

This is an interventional basic science trial for Hypercholesterolemia focused on measuring Phytosterols, Ezetimibe, Cholesterol Excretion, Cholesterol Absorption, Diet, Mass Spectrometry, Deuterium

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

Center for Advance Nutrition at Utah State University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Arm Label

Crossover order ABC

Crossover order BCA

Crossover order BAC

Crossover order ACB

Crossover order CAB

Crossover order CBA

Arm Description

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

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

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

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

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

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

Outcomes

Primary Outcome Measures

Cholesterol Excretion

Milligrams of fecal cholesterol and cholesterol metabolites excreted per day

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.

LDL Cholesterol

Secondary Outcome Measures

Full Information

NCT ID

NCT00863265

First Posted

March 16, 2009

Last Updated

May 29, 2018

Sponsor

Washington University School of Medicine

Collaborators

Utah State University, National Heart, Lung, and Blood Institute (NHLBI)

1. Study Identification

Unique Protocol Identification Number

NCT00863265

Brief Title

Phytosterols, Ezetimibe, and Cholesterol Metabolism

Acronym

Phyteaux-III

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2018

Overall Recruitment Status

Completed

Study Start Date

June 2009 (undefined)

Primary Completion Date

October 2009 (Actual)

Study Completion Date

February 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Washington University School of Medicine

Collaborators

Utah State University, National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypercholesterolemia, Coronary Heart Disease

Keywords

Phytosterols, Ezetimibe, Cholesterol Excretion, Cholesterol Absorption, Diet, Mass Spectrometry, Deuterium

7. Study Design

Primary Purpose

Basic Science

Study Phase

Early Phase 1

Interventional Study Model

Crossover Assignment

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

ParticipantCare ProviderInvestigatorOutcomes 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.

Allocation

Randomized

Enrollment

22 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Crossover order ABC

Arm Type

Experimental

Arm Description

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

Arm Title

Crossover order BCA

Arm Type

Experimental

Arm Description

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

Arm Title

Crossover order BAC

Arm Type

Experimental

Arm Description

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

Arm Title

Crossover order ACB

Arm Type

Experimental

Arm Description

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

Arm Title

Crossover order CAB

Arm Type

Experimental

Arm Description

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

Arm Title

Crossover order CBA

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Ezetimibe

Other Intervention Name(s)

Intervention Description

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

Intervention Name(s)

Phytosterols + ezetimibe

Other Intervention Name(s)

Intervention Description

Intervention Type

Other

Intervention Name(s)

Placebo

Other Intervention Name(s)

Primary Outcome Measure Information:

Title

Cholesterol Excretion

Description

Milligrams of fecal cholesterol and cholesterol metabolites excreted per day

Time Frame

At the end of week 3 on each diet

Title

Percent Cholesterol Absorption

Description

Time Frame

Determined on the final 5 days of each dietary period

Title

LDL Cholesterol

Time Frame

At the end of week 3 on each diet

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Richard Ostlund, M.D.

Organizational Affiliation

Washington University School of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Center for Advance Nutrition at Utah State University

City

Logan

State/Province

Utah

ZIP/Postal Code

84322-4715

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

21768544

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.

Results Reference

result

Learn more about this trial

Phytosterols, Ezetimibe, and Cholesterol Metabolism

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