Phytosterols, Ezetimibe, and Cholesterol Metabolism (Phyteaux-III)
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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) |
- Cholesterol Absorption and Excretion [ Time Frame: At the end of week 3 on each diet ] [ Designated as safety issue: No ]
- 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 |
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| United States, Utah | |
| Center for Advance Nutrition at Utah State University | |
| Logan, Utah, United States, 84322-4715 | |
| 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 Myocardial Ischemia Coronary Disease Heart Diseases Hypercholesterolemia Cardiovascular Diseases Arteriosclerosis Arterial Occlusive Diseases Vascular Diseases Hyperlipidemias Dyslipidemias |
Lipid Metabolism Disorders Metabolic Diseases Ezetimibe Anticholesteremic Agents Hypolipidemic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Lipid Regulating Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on May 21, 2013