Brief 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. 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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at below P25 for phase_4

Timeline

Completed

Started Jun 2008

Shorter than P25 for phase_4

Geographic Reach

1 country

1 active site

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

9 months study duration

Study Start

First participant enrolled

June 1, 2008

Completed

16 days until next milestone

First Submitted

Initial submission to the registry

June 17, 2008

Completed

2 days until next milestone

First Posted

Study publicly available on registry

June 19, 2008

Completed

9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2009

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2009

Completed

2.1 years until next milestone

Results Posted

Study results publicly available

April 18, 2011

Completed

Last Updated

April 18, 2011

Status Verified

March 1, 2011

Enrollment Period

9 months

First QC Date

June 17, 2008

Results QC Date

January 10, 2011

Last Update Submit

March 14, 2011

Conditions

Hypercholesterolemia

Keywords

metabolic diseasesmetabolic disorderdyslipidemiaslipid metabolism disorders

Outcome Measures

Primary Outcomes (1)

Fecal Excretion of Plasma-derived Cholesterol
(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.
7 weeks

Secondary Outcomes (6)

Change From Baseline in Total Cholesterol, From Fasting Plasma Samples
7 weeks
de Novo Cholesterol Synthesis (DNC)
7 weeks
Cholesterol Efflux Rate (Ra Cholesterol)
7 weeks
Triglycerides (TG)
7 weeks
Low-density Lipoprotein (LDL);
7 weeks
+1 more secondary outcomes

Study Arms (2)

1

EXPERIMENTAL

ezetimibe (10mg/day)for 7 weeks

Drug: ezetimibe

2

PLACEBO COMPARATOR

Placebo control

Drug: Placebo

Interventions

ezetimibeDRUG

1 tablet,10mg, once a day, for 7 weeks

PlaceboDRUG

1 tablet, once a day, for 7 weeks

Eligibility Criteria

Age21 Years - 75 Years

Sexall

Healthy VolunteersYes

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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
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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Radiant Researchlead

Study Sites (1)

Radiant Research

Chicago, Illinois, 60610, United States

Location

Related Publications (1)

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.
PMID: 24075764DERIVED

MeSH Terms

Conditions

HypercholesterolemiaMetabolic DiseasesDyslipidemiasLipid Metabolism Disorders

Interventions

Ezetimibe

Condition Hierarchy (Ancestors)

HyperlipidemiasNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

AzetidinesAzetinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Results Point of Contact

Title: Michael H Davidson, MD FACC
Organization: Radiant Research

Study Officials

Michael H Davidson, Md. FACC
Radiant Research
PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee: No
Restrictive Agreement: No

Study Design

Study Type: interventional
Phase: phase 4
Allocation: RANDOMIZED
Masking: NONE
Purpose: TREATMENT
Intervention Model: CROSSOVER
Sponsor Type: OTHER

Study Record Dates

First Submitted

June 17, 2008

First Posted

June 19, 2008

Study Start

June 1, 2008

Primary Completion

March 1, 2009

Study Completion

March 1, 2009

Last Updated

April 18, 2011

Results First Posted

April 18, 2011

Record last verified: 2011-03

Locations

US(1)

Brief Summary

Trial Health

Trial Health Score

Trial Relationships

Related Scientific Literature

Study Timeline

Study Start

First Submitted

First Posted

Primary Completion

Study Completion

Results Posted

Conditions

Keywords

Outcome Measures

Primary Outcomes (1)

Secondary Outcomes (6)

Study Arms (2)

1

2

Interventions

Eligibility Criteria

You may qualify if:

You may not qualify if:

Sponsors & Collaborators

Study Sites (1)

Related Publications (1)

MeSH Terms

Conditions

Interventions

Condition Hierarchy (Ancestors)

Intervention Hierarchy (Ancestors)

Results Point of Contact

Study Officials

Publication Agreements

Study Design

Study Record Dates

Locations