Ezetimibe Reverse Cholesterol Transport (RCT) Pilot Study - Full Text View

Sponsor:	Radiant Research
Information provided by:	Radiant Research
ClinicalTrials.gov Identifier:	NCT00701727

Purpose

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.

Condition	Intervention	Phase
Hypercholesterolemia	Drug: ezetimibe Drug: Placebo	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Ezetimibe Reverse Cholesterol Transport (RCT) Pilot Study

Resource links provided by NLM:

Genetics Home Reference related topics: hypercholesterolemia

MedlinePlus related topics: Cholesterol Metabolic Disorders

Drug Information available for: Cholest-5-en-3-ol (3beta)- Ezetimibe

U.S. FDA Resources

Further study details as provided by Radiant Research:

Primary Outcome Measures:

Fecal Excretion of Plasma-derived Cholesterol [ Time Frame: 7 weeks ] [ Designated as safety issue: No ]
(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.

Secondary Outcome Measures:

Change From Baseline in Total Cholesterol, From Fasting Plasma Samples [ Time Frame: 7 weeks ] [ Designated as safety issue: No ]
plasma levels of total cholesterol
de Novo Cholesterol Synthesis (DNC) [ Time Frame: 7 weeks ] [ Designated as safety issue: No ]
Plasma DNC will be measured following the isotope infusion of deuterated water, expressed as %.
Cholesterol Efflux Rate (Ra Cholesterol) [ Time Frame: 7 weeks ] [ Designated as safety issue: No ]
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.
Triglycerides (TG) [ Time Frame: 7 weeks ] [ Designated as safety issue: No ]
Change from baseline in plasma triglycerides, measured in fasting blood samples
Low-density Lipoprotein (LDL); [ Time Frame: 7 weeks ] [ Designated as safety issue: No ]
Change from baseline in plasma low-density lipoprotein(LDL), measured in fasting blood samples
High-density Lipoprotein (HDL) [ Time Frame: 7 weeks ] [ Designated as safety issue: No ]
Change from baseline in plasma HDL, measured in fasting blood samples

Enrollment:	31
Study Start Date:	June 2008
Study Completion Date:	March 2009
Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 ezetimibe (10mg/day)for 7 weeks	Drug: ezetimibe 1 tablet,10mg, once a day, for 7 weeks
Placebo Comparator: 2 Placebo control	Drug: Placebo 1 tablet, once a day, for 7 weeks

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.

Eligibility

Ages Eligible for Study:	21 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00701727

Locations

United States, Illinois
Radiant Research
Chicago, Illinois, United States, 60610

Sponsors and Collaborators

Radiant Research

Investigators

Principal Investigator:

Michael H Davidson, Md. FACC

Radiant Research

More Information

No publications provided

Responsible Party:	Michael H. Davidson, MD, FACC, Radiant Research
ClinicalTrials.gov Identifier:	NCT00701727 History of Changes
Other Study ID Numbers:	Ezetimibe RCT-001
Study First Received:	June 17, 2008
Results First Received:	January 10, 2011
Last Updated:	March 14, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Radiant Research:

metabolic diseases
metabolic disorder
dyslipidemias
lipid metabolism disorders

Additional relevant MeSH terms:

Hypercholesterolemia
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 February 09, 2012