HypercholesterolemiaPhase 4NCT00701727
Ezetimibe Reverse Cholesterol Transport (RCT) Pilot Study
A Phase 4 study testing ezetimibe in people with Hypercholesterolemia, run by Radiant Research at 1 site in United States.
Trial summary
This is a prospective, placebo-controlled, cross-over trial comparing the the effects of approximately 7 weeks of placebo treatment to 7 weeks of ezetimibe (10mg/day) treatment on several parameters of reverse cholesterol transport (RCT) in men and post-menopausal women diagnosed with hypercholesterolemia. Read more about this study
- Who is it for?
- Ages 21 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypercholesterolemia
- What is being tested?
- ezetimibe
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2008to Mar 2009
- Phase
- Phase 4
- 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 21 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- male, non-smoker, 21-75 years of age
- female, non-smoker, 40-75 years of age
- post-menopausal women, as defined by lack of menses for at least 2 years and age >55, OR history of documented bilateral oophorectomy, confirmed with an elevated FSH at screening
- low-density lipoprotein (LDL) concentration between 130-200 mg/dL.
- triglyceride (TG) concentration <350 mg/dL, inclusive
- high-density lipoprotein (HDL) between 30-60 mg/dL for men and 40 -70 mg/dL for women
- ability to give informed consent
Who cannot join
- Subject has history of diabetes mellitus, active hepatitis, gall bladder disease, gastric or ileal bypass surgery, irritable bowel syndrome, and gastrointestinal disorder/condition associated with malabsorption, or clinically significant abnormalities on screening (prestudy) physical examination of laboratory tests.
- Screening laboratory tests with hematocrit <30%, aspartate aminotransferase/alanine aminotransferase (AST/ALT) >2*upper limit of normal, abnormal thyroid-stimulating hormone (TSH), fasting glucose >=126mg/dL
- renal impairment with creatinine clearance (CRCl)<80ml/min
- treatment within the last 2 months with drugs known to alter lipid metabolism including beta blockers, thiazide diuretics, bile acid resins, statins, ezetimibe, niacin, fibrates, plant stanol esters (eg Benecol,phyto sterols) and fishoils
- history of known coronary heart disease (CHD), stroke or prior revascularization procedure or peripheral vascular disease
- history of allergy to egg or soy products
Show all 9Show fewer
- current or recent (past 12 months) of drug abuse or alcohol abuse. Alcohol use must be limited to no more than 2 drinks/day (1 drink=12 oz beer, 5 oz wine, or 1.5 oz hard liquor). Subject must be willing to avoid large day-to-day fluctuations in alcohol intake.
- participation in another clinical trial or exposure to any investigational agent within 30 days prior to Visit 1
- Individual has a condition the Principal Investigator believes would interfere with his/her ability to provide informed consent, comply with study instructions, or which might confound the interpretation of the study results, or put the subject at undue risk
Trial locations and contacts
1 site in 1 country.
About this study
This is a prospective, placebo-controlled, cross-over trial comparing the the effects of approximately 7 weeks of placebo treatment to 7 weeks of ezetimibe (10mg/day) treatment on several parameters of reverse cholesterol transport (RCT) in men and post-menopausal women diagnosed with hypercholesterolemia. The primary hypothesis is that the ezetimibe treatment will increase the excretion of endogenous (plasma-derived) cholesterol as fecal sterols, with secondary hypotheses that there will be a significant increase in de novo cholesterol synthesis, treatment will increase cholesterol efflux from tissues into the bloodstream, and increase global RCT.
Read the detailed description
The study will compare the effects of approximately 7 weeks of placebo treatment to 7 weeks of ezetimibe (10mg/day) on: 1) the efficiency of endogenous (plasma-derived) cholesterol excretion (%/day) 2) de novo cholesterol (DNC) synthesis ((%/day) 3) cholesterol efflux from tissues into blood (Ra), and 4) global RCT (efflux from tissues that is excreted as fecal sterols). Subjects will receive 7 weeks of either treatment or placebo, undergo RCT and DNC measurements, taking 10 days, then cross-over to the alternate placebo or treatment for an additional 7 weeks, followed by a second set of RCT and DNC measurements.
- Conditions
- Hypercholesterolemia
- Being tested
- ezetimibe, Placebo
- Keywords
- metabolic diseases, metabolic disorder, dyslipidemias, lipid metabolism disorders
- Medical subject headings
- Hypercholesterolemia, Metabolic Diseases, Dyslipidemias, Lipid Metabolism Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ezetimibeDrug
1 tablet,10mg, once a day, for 7 weeks
PlaceboDrug
1 tablet, once a day, for 7 weeks
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | ezetimibe (10mg/day)for 7 weeks Receives: Drug: ezetimibe |
| 2 | Placebo comparator | Placebo control Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fecal Excretion of Plasma-derived Cholesterol
(Fecal excretion of plasma-derived cholesterol):The following measurements will be made following isotope infusion:
- The composition of fecal neutral and acidic sterols will be measured as % of total.
- The excretion rate of fecal neutral and acidic sterols will be measured as mg/day.
- The isotopic enrichment of both fecal neutral and acidic sterols will be measured as atomic percent excess (% APE).
- Fecal isotope excretion, or recovery, of plasma-derived cholesterol will be calculated as %/day.
Measured: 7 weeks
Secondary outcomes (6)
Change From Baseline in Total Cholesterol, From Fasting Plasma Samples
plasma levels of total cholesterol
Measured: 7 weeks
de Novo Cholesterol Synthesis (DNC)
Plasma DNC will be measured following the isotope infusion of deuterated water, expressed as %.
Measured: 7 weeks
Cholesterol Efflux Rate (Ra Cholesterol)
The efflux, or mobilization, rate of cholesterol from peripheral tissues into the plasma will be measured as mg/kg/hr. An IV infusion of [13C2] cholesterol mixed in 10% Intralipid® and 10 % ethanol is given piggy-backed into normal saline over 20 hours (4pm - 12 noon). This is used to determine rate of appearance (Ra) cholesterol, which will be measured by dilution of infused [13C2] cholesterol during the plateau phase of plasma enrichment (approximately the last 4 hours of the infusion), as well as to provide the plasma cholesterol that will be traced into biliary sterols.
Measured: 7 weeks
Triglycerides (TG)
Change from baseline in plasma triglycerides, measured in fasting blood samples
Measured: 7 weeks
Low-density Lipoprotein (LDL);
Change from baseline in plasma low-density lipoprotein(LDL), measured in fasting blood samples
Measured: 7 weeks
High-density Lipoprotein (HDL)
Change from baseline in plasma HDL, measured in fasting blood samples
Measured: 7 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2008 (estimated)
- Study startJun 2008
- Primary completionMar 2009
- Study completionMar 2009
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.
- 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
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radiant Research
- Sponsor type
- University, hospital or other
- Investigators
- Michael H Davidson, Md. FACC, Principal investigator, Radiant Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00701727
- Sponsor's protocol ID
- Ezetimibe RCT-001
- Status last verified
- Mar 2011
- First submitted
- 17 Jun 2008
- Last updated
- 18 Apr 2011
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Davidson MH, Voogt J, Luchoomun J, Decaris J, Killion S, Boban D, Glass A, Mohammad H, Lu Y, Villegas D, Neese R, Hellerstein M, Neff D, Musliner T, Tomassini JE, Turner S. Inhibition of intestinal cholesterol absorption with ezetimibe increases components of reverse cholesterol transport in humans. Atherosclerosis. 2013 Oct;230(2):322-9. doi: 10.1016/j.atherosclerosis.2013.08.006. Epub 2013 Aug 13.
PubMed 24075764
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ezetimibe Reverse Cholesterol Transport (RCT) Pilot Study
- ClinicalTrials.gov ID
- NCT00701727
- Acronym / sponsor ID
- Ezetimibe RCT-001
- Conditions
- Hypercholesterolemia
- Keywords
- metabolic diseases, metabolic disorder, dyslipidemias, lipid metabolism disorders
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Radiant ResearchUniversity, hospital or other
- Study start
- Jun 2008
- Primary completion
- Mar 2009 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 19 Jun 2008 (estimated)
- Results
- Posted 18 Apr 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a prospective, placebo-controlled, cross-over trial comparing the the effects of approximately 7 weeks of placebo treatment to 7 weeks of ezetimibe (10mg/day) treatment on several parameters of reverse cholesterol transport (RCT) in men and post-menopausal women diagnosed with hypercholesterolemia. The primary hypothesis is that the ezetimibe treatment will increase the excretion of endogenous (plasma-derived) cholesterol as fecal sterols, with secondary hypotheses that there will be a significant increase in de novo cholesterol synthesis, treatment will increase cholesterol efflux from tissues into the bloodstream, and increase global RCT.
Detailed description
The study will compare the effects of approximately 7 weeks of placebo treatment to 7 weeks of ezetimibe (10mg/day) on: 1) the efficiency of endogenous (plasma-derived) cholesterol excretion (%/day) 2) de novo cholesterol (DNC) synthesis ((%/day) 3) cholesterol efflux from tissues into blood (Ra), and 4) global RCT (efflux from tissues that is excreted as fecal sterols). Subjects will receive 7 weeks of either treatment or placebo, undergo RCT and DNC measurements, taking 10 days, then cross-over to the alternate placebo or treatment for an additional 7 weeks, followed by a second set of RCT and DNC measurements.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: ezetimibeezetimibe (10mg/day)for 7 weeks |
| 2 | Placebo comparator | Drug: PlaceboPlacebo control |
Who may qualify
- Ages
- 21 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- male, non-smoker, 21-75 years of age
- female, non-smoker, 40-75 years of age
- post-menopausal women, as defined by lack of menses for at least 2 years and age >55, OR history of documented bilateral oophorectomy, confirmed with an elevated FSH at screening
- low-density lipoprotein (LDL) concentration between 130-200 mg/dL.
- triglyceride (TG) concentration <350 mg/dL, inclusive
Key exclusion criteria (9 listed)
- Subject has history of diabetes mellitus, active hepatitis, gall bladder disease, gastric or ileal bypass surgery, irritable bowel syndrome, and gastrointestinal disorder/condition associated with malabsorption, or clinically significant abnormalities on screening (prestudy) physical examination of laboratory tests.
- Screening laboratory tests with hematocrit <30%, aspartate aminotransferase/alanine aminotransferase (AST/ALT) >2*upper limit of normal, abnormal thyroid-stimulating hormone (TSH), fasting glucose >=126mg/dL
- renal impairment with creatinine clearance (CRCl)<80ml/min
- treatment within the last 2 months with drugs known to alter lipid metabolism including beta blockers, thiazide diuretics, bile acid resins, statins, ezetimibe, niacin, fibrates, plant stanol esters (eg Benecol,phyto sterols) and fishoils
- history of known coronary heart disease (CHD), stroke or prior revascularization procedure or peripheral vascular 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 |
|---|---|---|
| ezetimibe1 tablet,10mg, once a day, for 7 weeks | Drug | 1 |
| Placebo1 tablet, once a day, for 7 weeks | Drug | 2 |
Primary outcome
Fecal Excretion of Plasma-derived Cholesterol
Time frame: 7 weeks
(Fecal excretion of plasma-derived cholesterol):The following measurements will be made following isotope infusion: 1. The composition of fecal neutral and acidic sterols will be measured as % of total. 2. The excretion rate of fecal neutral and acidic sterols will be measured as mg/day. 3. The isotopic enrichment of both fecal neutral and acidic sterols will be measured as atomic percent excess (% APE). 4. Fecal isotope excretion, or recovery, of plasma-derived cholesterol will be calculated as %/day.
6 secondary outcomes
Change From Baseline in Total Cholesterol, From Fasting Plasma Samples
Time frame: 7 weeks
de Novo Cholesterol Synthesis (DNC)
Time frame: 7 weeks
Cholesterol Efflux Rate (Ra Cholesterol)
Time frame: 7 weeks
Triglycerides (TG)
Time frame: 7 weeks
Low-density Lipoprotein (LDL);
Time frame: 7 weeks
High-density Lipoprotein (HDL)
Time frame: 7 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2011.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24075764Davidson MH, Voogt J, Luchoomun J, Decaris J, Killion S, Boban D, Glass A, Mohammad H, Lu Y, Villegas D, Neese R, Hellerstein M, Neff D, Musliner T, Tomassini JE, Turner S. Inhibition of intestinal cholesterol absorption with ezetimibe increases components of reverse cholesterol transport in humans. Atherosclerosis. 2013 Oct;230(2):322-9. doi: 10.1016/j.atherosclerosis.2013.08.006. Epub 2013 Aug 13.
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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.
Michael H Davidson, Md. FACC principal investigator
Radiant Research
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing ezetimibe in people with Hypercholesterolemia, run by Radiant Research at 1 site in United States.
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 9 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 18 Apr 2011. 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. Some participants in this study may receive a placebo. 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?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 18 Apr 2011). 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?
Fecal Excretion of Plasma-derived Cholesterol (time frame: 7 weeks). 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 NCT00701727, 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 18 Apr 2011.