Phytosterols, Ezetimibe, and Cholesterol Metabolism

NCT00863265 | Completed Early Phase 1 Results DMC

• 2 other identifiers: CANUSU-phyto3R01HL050420
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypercholesterolemia; Coronary Heart Disease

Keywords

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

Outcome Measures

Primary Outcomes (3)

• Cholesterol Excretion

  Milligrams of fecal cholesterol and cholesterol metabolites excreted per day

  At the end of week 3 on each diet

• 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

• LDL Cholesterol

  At the end of week 3 on each diet

Study Arms (6)

Crossover order ABC

EXPERIMENTAL

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

Drug: Ezetimibe; Other: Phytosterols + ezetimibe; Other: Placebo

Crossover order BCA

EXPERIMENTAL

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

Drug: Ezetimibe; Other: Phytosterols + ezetimibe; Other: Placebo

Crossover order BAC

EXPERIMENTAL

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

Drug: Ezetimibe; Other: Phytosterols + ezetimibe; Other: Placebo

Crossover order ACB

EXPERIMENTAL

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

Drug: Ezetimibe; Other: Phytosterols + ezetimibe; Other: Placebo

Crossover order CAB

EXPERIMENTAL

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

Drug: Ezetimibe; Other: Phytosterols + ezetimibe; Other: Placebo

Crossover order CBA

EXPERIMENTAL

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

Drug: Ezetimibe; Other: Phytosterols + ezetimibe; Other: Placebo

Interventions

Ezetimibe 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.

Also known as: C

Crossover order ABC; Crossover order ACB; Crossover order BAC; Crossover order BCA; Crossover order CAB; Crossover order CBA

Phytosterols + ezetimibe 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.

Also known as: A

Crossover order ABC; Crossover order ACB; Crossover order BAC; Crossover order BCA; Crossover order CAB; Crossover order CBA

Placebo OTHER

Also known as: B

Crossover order ABC; Crossover order ACB; Crossover order BAC; Crossover order BCA; Crossover order CAB; Crossover order CBA

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Utah State University: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Center for Advance Nutrition at Utah State University

Logan, Utah, 84322-4715, United States

Location

Related 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/CIRCULATIONAHA.110.006692. Epub 2011 Jul 18.

  PMID: 21768544 RESULT

MeSH Terms

Conditions

Hypercholesterolemia; Coronary Disease

Interventions

Ezetimibe; Phytosterols

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Sterols; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Membrane Lipids; Lipids; Phytochemicals; Biological Factors

Results Point of Contact

• Title: Richard E. Ostlund MD
• Organization: Washington University School of Medicine

rostlund@wustl.edu

314-362-3516

Study Officials

• Richard Ostlund, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 16, 2009
• First Posted: March 17, 2009
• Study Start: June 1, 2009
• Primary Completion: October 1, 2009
• Study Completion: February 1, 2010
• Last Updated: June 1, 2018
• Results First Posted: June 1, 2018

Record last verified: 2018-05

Locations

US (1)