HypercholesterolemiaEarly Phase 1Phyteaux-IIINCT00863265

Phytosterols, Ezetimibe, and Cholesterol Metabolism

A Early Phase 1 study testing Ezetimibe and Phytosterols + ezetimibe in people with Hypercholesterolemia and Coronary Heart Disease, run by Washington University School of Medicine at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 80 yearsHealthy volunteers can take part
Conditions the study is for: Hypercholesterolemia, Coronary Heart Disease
What is being tested?: Ezetimibe and Phytosterols + ezetimibe
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 22 participants
Where: 1 siteUnited States
Study dates: Jun 2009to Feb 2010
Phase: Early Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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.

Who cannot join

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;

Show all 16Show fewer

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Center for Advance Nutrition at Utah State University
Logan, Utah, 84322-4715

Other trials in United States

About this study

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

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.

Read the 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.

Conditions: Hypercholesterolemia, Coronary Heart Disease
Being tested: Ezetimibe, Phytosterols + ezetimibe, Placebo
Keywords: Phytosterols, Ezetimibe, Cholesterol Excretion, Cholesterol Absorption, Diet, Mass Spectrometry, Deuterium
Medical subject headings: Hypercholesterolemia, Coronary Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EzetimibeDrug
Also called C
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.
Phytosterols + ezetimibeOther
Also called A
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.
PlaceboOther
Also called B

Study groups in NCT00863265
Study group	Role	What they receive
Crossover order ABC	Experimental	The order of treatments is A (phytosterols + ezetimibe), B (double placebo), and C (active ezetimibe and phytosterol placebo). Receives: 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). Receives: 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) Receives: 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). Receives: 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). Receives: 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). Receives: Drug: Ezetimibe; Other: Phytosterols + ezetimibe; Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Cholesterol Excretion
Milligrams of fecal cholesterol and cholesterol metabolites excreted per day
Measured: 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.
Measured: Determined on the final 5 days of each dietary period
LDL Cholesterol
Measured: At the end of week 3 on each diet

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2009Feb 2010

First posted17 Mar 2009 (estimated)
Study startJun 2009
Primary completionOct 2009
Study completionFeb 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HypercholesterolemiaStudies of the same condition, open and under way.
More trials run by Washington University School of MedicineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Early Phase 1
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
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: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 22 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00863265
Sponsor's protocol ID: CANUSU-phyto3
Other IDs: R01HL050420
Acronym: Phyteaux-III
Status last verified: May 2018
First submitted: 16 Mar 2009
Last updated: 1 Jun 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 21768544

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Hypercholesterolemia trials

Study at a glance

From the registry record, last updated by the sponsor on 1 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Regulation of Cholesterol Absorption: LDL Cholesterol Response to a Combination of Phytosterols and Ezetimibe (Phyto-3)
ClinicalTrials.gov ID: NCT00863265
Acronym / sponsor ID: Phyteaux-III / CANUSU-phyto3
Conditions: Hypercholesterolemia, Coronary Heart Disease
Keywords: Phytosterols, Ezetimibe, Cholesterol Excretion, Cholesterol Absorption, Diet, Mass Spectrometry, Deuterium
Phase: Early Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 22 participants (actual)
Lead sponsor: Washington University School of MedicineUniversity, hospital or other
Collaborators: Utah State University, National Heart, Lung, and Blood Institute (NHLBI)
Study start: Jun 2009
Primary completion: Oct 2009 (actual)
Study completion: Feb 2010 (actual)
First posted: 17 Mar 2009 (estimated)
Results: Posted 1 Jun 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 6
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.

Arm	Type	Receives
Crossover order ABC	Experimental	Drug: Ezetimibe, Other: Phytosterols + ezetimibe, Other: PlaceboThe order of treatments is A (phytosterols + ezetimibe), B (double placebo), and C (active ezetimibe and phytosterol placebo).
Crossover order BCA	Experimental	Drug: Ezetimibe, Other: Phytosterols + ezetimibe, Other: PlaceboThe order of treatments is B (double placebo), C (active ezetimibe and phytosterol placebo), and A (phytosterols + ezetimibe).
Crossover order BAC	Experimental	Drug: Ezetimibe, Other: Phytosterols + ezetimibe, Other: PlaceboThe order of treatments is B (double placebo), A (phytosterols + ezetimibe), and C (active ezetimibe and phytosterol placebo)
Crossover order ACB	Experimental	Drug: Ezetimibe, Other: Phytosterols + ezetimibe, Other: PlaceboThe order of treatments is A (phytosterols + ezetimibe), C (active ezetimibe and placebo phytosterols, and B (double placebo).
Crossover order CAB	Experimental	Drug: Ezetimibe, Other: Phytosterols + ezetimibe, Other: PlaceboThe order of treatments is C (active ezetimibe and placebo phytosterols), A (phytosterols + ezetimibe), and B (double placebo).
Crossover order CBA	Experimental	Drug: Ezetimibe, Other: Phytosterols + ezetimibe, Other: PlaceboThe order of treatments is C (active ezetimibe and placebo phytosterols), B (double placebo), and A (phytosterols and ezetimibe).

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

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;

Key exclusion criteria (16 listed)

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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
EzetimibeAlso: CSubjects 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.	Drug	Crossover order ABC, Crossover order ACB, Crossover order BAC, Crossover order BCA, Crossover order CAB, Crossover order CBA
Phytosterols + ezetimibeAlso: ASubjects 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.	Other	Crossover order ABC, Crossover order ACB, Crossover order BAC, Crossover order BCA, Crossover order CAB, Crossover order CBA
PlaceboAlso: B	Other	Crossover order ABC, Crossover order ACB, Crossover order BAC, Crossover order BCA, Crossover order CAB, Crossover order CBA

Primary outcome

Cholesterol Excretion
Time frame: At the end of week 3 on each diet
Milligrams of fecal cholesterol and cholesterol metabolites excreted per day
Percent Cholesterol Absorption
Time frame: Determined on the final 5 days of each dietary period
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
Time frame: At the end of week 3 on each diet

Results and safety

Results posted to the registry on 1 Jun 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Crossover Order ABC	4	4
Crossover Order BCA	3	3
Crossover Order BAC	4	4
Crossover Order ACB	4	4
Crossover Order CAB	4	3
Crossover Order CBA	3	3

Primary outcome: Cholesterol Excretion

Time frame: At the end of week 3 on each diet. Mean (95% Confidence Interval). Unit: mg per day

Measure	Phytosterol-Deficient Diet n = 21	Diet Plus Ezetimibe n = 21	Diet Plus Ezetimibe Plus Phytosterols n = 21
Value	505 (386 to 625)	794 (615 to 973)	962 (757 to 1168)

Phytosterol-Deficient Diet vs Diet Plus Ezetimibe: Mean Difference (Final Values): 289, p = 0.01, ANOVA
Phytosterol-Deficient Diet vs Diet Plus Ezetimibe Plus Phytosterols: Mean Difference (Final Values): 457, p <0.01, ANOVA
Diet Plus Ezetimibe vs Diet Plus Ezetimibe Plus Phytosterols: Mean Difference (Final Values): 168, p <0.01, ANOVA

Population analysed: Healthy subjects

Primary outcome: Percent Cholesterol Absorption

Time frame: Determined on the final 5 days of each dietary period. Mean (95% Confidence Interval). Unit: Percent

Measure	Phytosterol-Deficient Diet n = 21	Diet Plus Ezetimibe n = 21	Diet Plus Ezetimibe Plus Phytosterols n = 21
Value	69.0 (61.8 to 76.2)	46.2 (38.5 to 53.9)	32.6 (26.9 to 38.3)

Phytosterol-Deficient Diet vs Diet Plus Ezetimibe: Mean Difference (Final Values): 22.8, p <0.01, ANOVA
Phytosterol-Deficient Diet vs Diet Plus Ezetimibe Plus Phytosterols: Mean Difference (Final Values): 36.4, p <0.01, ANOVA
Diet Plus Ezetimibe vs Diet Plus Ezetimibe Plus Phytosterols: Mean Difference (Final Values): 13.6, p <0.01, ANOVA

Primary outcome: LDL Cholesterol

Time frame: At the end of week 3 on each diet. Mean (95% Confidence Interval). Unit: mg/deciliter

Measure	Phytosterol-Deficient Diet n = 21	Phytosterol-Deficient Diet Plus Ezetimibe n = 21	Phytosterol-Deficient Diet Plus Ezetimibe Plus Phytosterols n = 21
Value	129 (116 to 142)	108 (97 to 119)	101 (90 to 112)

Phytosterol-Deficient Diet vs Phytosterol-Deficient Diet Plus Ezetimibe: Mean Difference (Final Values): 21, p <0.01, ANOVA
Phytosterol-Deficient Diet vs Phytosterol-Deficient Diet Plus Ezetimibe Plus Phytosterols: Mean Difference (Final Values): 28, p <0.01, ANOVA
Phytosterol-Deficient Diet Plus Ezetimibe vs Phytosterol-Deficient Diet Plus Ezetimibe Plus Phytosterols: Mean Difference (Final Values): 7, p <0.05, ANOVA

Population analysed: Healthy subjects

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Phytosterol-Deficient Diet	0 of 22 (0%)	0 of 22 (0%)	0 of 22
Diet Plus Ezetimibe	0 of 22 (0%)	0 of 22 (0%)	0 of 22
Diet Plus Ezetimibe Plus Phytosterols	0 of 22 (0%)	0 of 22 (0%)	0 of 22

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 21768544Lin 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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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Richard Ostlund, M.D. principal investigator

Washington University School of Medicine

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Jun 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cholesterol Excretion (time frame: At the end of week 3 on each diet). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00863265, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2018; AzTrials last refreshed its copy on 31 Oct 2026.