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| ID | Type | Description | Link |
|---|---|---|---|
| R01HL050420 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Utah State University | OTHER |
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Crossover order ABC | Experimental | The order of treatments is A (phytosterols + ezetimibe), B (double placebo), and C (active ezetimibe and phytosterol placebo). |
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| Crossover order BCA | Experimental | The order of treatments is B (double placebo), C (active ezetimibe and phytosterol placebo), and A (phytosterols + ezetimibe). |
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| Crossover order BAC | Experimental | The order of treatments is B (double placebo), A (phytosterols + ezetimibe), and C (active ezetimibe and phytosterol placebo) |
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| Crossover order ACB | Experimental | The order of treatments is A (phytosterols + ezetimibe), C (active ezetimibe and placebo phytosterols, and B (double placebo). |
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| Crossover order CAB | Experimental | The order of treatments is C (active ezetimibe and placebo phytosterols), A (phytosterols + ezetimibe), and B (double placebo). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Richard Ostlund, M.D. | Washington University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Center for Advance Nutrition at Utah State University | Logan | Utah | 84322-4715 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21768544 | Result | 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. |
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175 subjects were screened and 153 were excluded prior to randomization. 75 did not meet screening criteria, 39 declined to participate and 39 were not able to perform functions needed for the study. 22 Subjects were randomized and 21 completed the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Crossover Order ABC | Subjects will undergo 3 periods of 21 days on a controlled diet plus phytosterols/placebo and ezetimibe/placebo. A washout of 7 days occurs between periods. A. Phytosterols 2000 mg/day and ezetimibe 10 mg/day. B. Phytosterol placebo and ezetimibe placebo. C. Phytosterol placebo and active ezetimibe 10 mg/day. ezetimibe plus phytosterols. |
| FG001 | Crossover Order BCA | Subjects will undergo 3 periods of 21 days on a controlled diet plus phytosterols/placebo and ezetimibe/placebo. A washout of 7 days occurs between periods. A. Phytosterols 2000 mg/day and ezetimibe 10 mg/day. B. Phytosterol placebo and ezetimibe placebo. C. Phytosterol placebo and active ezetimibe 10 mg/day. ezetimibe plus phytosterols. |
| FG002 | Crossover Order BAC | Subjects will undergo 3 periods of 21 days on a controlled diet plus phytosterols/placebo and ezetimibe/placebo. A washout of 7 days occurs between periods. A. Phytosterols 2000 mg/day and ezetimibe 10 mg/day. B. Phytosterol placebo and ezetimibe placebo. C. Phytosterol placebo and active ezetimibe 10 mg/day. ezetimibe plus phytosterols. |
| FG003 | Crossover Order ACB | Subjects will undergo 3 periods of 21 days on a controlled diet plus phytosterols/placebo and ezetimibe/placebo. A washout of 7 days occurs between periods. A. Phytosterols 2000 mg/day and ezetimibe 10 mg/day. B. Phytosterol placebo and ezetimibe placebo. C. Phytosterol placebo and active ezetimibe 10 mg/day. ezetimibe plus phytosterols. |
| FG004 | Crossover Order CAB | Subjects will undergo 3 periods of 21 days on a controlled diet plus phytosterols/placebo and ezetimibe/placebo. A washout of 7 days occurs between periods. A. Phytosterols 2000 mg/day and ezetimibe 10 mg/day. B. Phytosterol placebo and ezetimibe placebo. C. Phytosterol placebo and active ezetimibe 10 mg/day. ezetimibe plus phytosterols. |
| FG005 | Crossover Order CBA | Subjects will undergo 3 periods of 21 days on a controlled diet plus phytosterols/placebo and ezetimibe/placebo. A washout of 7 days occurs between periods. A. Phytosterols 2000 mg/day and ezetimibe 10 mg/day. B. Phytosterol placebo and ezetimibe placebo. C. Phytosterol placebo and active ezetimibe 10 mg/day. ezetimibe plus phytosterols. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants | All study participants. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Cholesterol Excretion | Milligrams of fecal cholesterol and cholesterol metabolites excreted per day | Healthy subjects | Posted | Mean | 95% Confidence Interval | mg per day | At the end of week 3 on each diet |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Phytosterol-Deficient Diet | Phytosterol-deficient diet plus ezetimibe placebo plus phytosterol placebo. 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. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Richard E. Ostlund MD | Washington University School of Medicine | 314-362-3516 | rostlund@wustl.edu |
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| ID | Term |
|---|---|
| D006937 | Hypercholesterolemia |
| D003327 | Coronary Disease |
| ID | Term |
|---|---|
| D006949 | Hyperlipidemias |
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
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| ID | Term |
|---|---|
| D000069438 | Ezetimibe |
| D010840 | Phytosterols |
| ID | Term |
|---|---|
| D001384 | Azetidines |
| D001385 | Azetines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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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.
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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.
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| Crossover order CBA | Experimental | The order of treatments is C (active ezetimibe and placebo phytosterols), B (double placebo), and A (phytosterols and ezetimibe). |
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| 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. |
|
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| Placebo | Other |
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| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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Phytosterol-deficient diet plus 10 mg/day of ezetimibe plus phytosterol placebo. 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. |
| OG002 | Diet Plus Ezetimibe Plus Phytosterols | Phytosterol-deficient diet plus 10 mg/day of ezetimibe plus 2000 mg/day of phytosterols. 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. |
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|
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| Primary | 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. | Posted | Mean | 95% Confidence Interval | Percent | Determined on the final 5 days of each dietary period |
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| Primary | LDL Cholesterol | Healthy subjects | Posted | Mean | 95% Confidence Interval | mg/deciliter | At the end of week 3 on each diet |
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|
|
|
| 0 |
| 22 |
| 0 |
| 22 |
| 0 |
| 22 |
| EG001 | Diet Plus Ezetimibe | Phytosterol-deficient diet plus 10 mg/day of ezetimibe plus phytosterol placebo. 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. | 0 | 22 | 0 | 22 | 0 | 22 |
| EG002 | Diet Plus Ezetimibe Plus Phytosterols | Phytosterol-deficient diet plus 10 mg/day of ezetimibe plus 2000 mg/day of phytosterols. 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. | 0 | 22 | 0 | 22 | 0 | 22 |
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| D009750 |
| Nutritional and Metabolic Diseases |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
| D013261 |
| Sterols |
| D002776 | Cholestanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D008563 | Membrane Lipids |
| D008055 | Lipids |
| D064209 | Phytochemicals |
| D001685 | Biological Factors |
Placebo vs. Ezetimibe Plus Phytosterols
| ANOVA |
| <0.01 |
Adjusted for multiple comparisons. |
| Mean Difference (Final Values) |
| 36.4 |
| 2-Sided |
| Equivalence |
| The hypothesis is that groups are equal. | ANOVA | <0.01 | Adjusted for multiple comparisons. | Mean Difference (Final Values) | 13.6 | 2-Sided | Equivalence |
| <0.01 |
Adjusted for multiple comparisons. |
| Mean Difference (Final Values) |
| 28 |
| 2-Sided |
| Equivalence |
| The hypothesis is that groups are equal. | ANOVA | <0.05 | Adjusted for multiple comparisons. | Mean Difference (Final Values) | 7 | 2-Sided | Equivalence |