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

This study has been completed.
Sponsor:
Collaborator:
Utah State University
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00863265
First received: March 16, 2009
Last updated: May 2, 2012
Last verified: May 2012
  Purpose

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 nearly completely. 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 in random order. During period I placebo phytosterols and placebo ezetimibe will be given; during period II placebo phytosterols and active ezetimibe will be given; during period III active phytosterols and active ezetimibe will be given. Study endpoints are fecal cholesterol excretion and percent cholesterol absorption determined by gas chromatography/mass spectrometry, circulating phytosterol levels and circulating LDL cholesterol levels.


Condition Intervention
Hypercholesterolemia
Coronary Heart Disease
Drug: Phytosterol-Deficient Diet, Ezetimibe 10 mg, Phytosterol Esters Containing 2000 mg Phytosterols

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Regulation of Cholesterol Absorption: LDL Cholesterol Response to a Combination of Phytosterols and Ezetimibe (Phyto-3)

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Cholesterol Absorption and Excretion [ Time Frame: At the end of week 3 on each diet ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • LDL cholesterol [ Time Frame: At the end of week 3 on each diet ] [ Designated as safety issue: No ]

Enrollment: 22
Study Start Date: June 2009
Study Completion Date: February 2010
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Phytosterol-Deficient Diet
Phytosterol-deficient diet plus ezetimibe placebo plus phytosterol placebo.
Drug: Phytosterol-Deficient Diet, Ezetimibe 10 mg, Phytosterol Esters Containing 2000 mg Phytosterols
Subjects will undergo three diet periods of 21 days each. Food will be supplied by a metabolic kitchen and will consist of a phytosterol-deficient baseline diet. Subjects will also receive either no active treatment, ezetimibe, or ezetimibe plus phytosterols.
Active Comparator: Diet Plus Ezetimibe
Phytosterol-deficient diet plus 10 mg/day of ezetimibe plus phytosterol placebo.
Drug: Phytosterol-Deficient Diet, Ezetimibe 10 mg, Phytosterol Esters Containing 2000 mg Phytosterols
Subjects will undergo three diet periods of 21 days each. Food will be supplied by a metabolic kitchen and will consist of a phytosterol-deficient baseline diet. Subjects will also receive either no active treatment, ezetimibe, or ezetimibe plus phytosterols.
Active Comparator: Diet Plus Ezetimibe plus Phytosterols
Phytosterol-deficient diet plus 10 mg/day of ezetimibe plus 2000 mg/day of phytosterols.
Drug: Phytosterol-Deficient Diet, Ezetimibe 10 mg, Phytosterol Esters Containing 2000 mg Phytosterols
Subjects will undergo three diet periods of 21 days each. Food will be supplied by a metabolic kitchen and will consist of a phytosterol-deficient baseline diet. Subjects will also receive either no active treatment, ezetimibe, or ezetimibe plus phytosterols.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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
Investigators
Principal Investigator: Richard Ostlund, M.D. Washington University School of Medicine
  More Information

Publications:
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00863265     History of Changes
Other Study ID Numbers: CANUSU-phyto3, R01 HL50420
Study First Received: March 16, 2009
Last Updated: May 2, 2012
Health Authority: United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on October 21, 2014