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Ezetimibe Reverse Cholesterol Transport (RCT) Pilot Study

This study has been completed.
Information provided by:
Radiant Research Identifier:
First received: June 17, 2008
Last updated: March 14, 2011
Last verified: March 2011
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
Drug: ezetimibe
Drug: Placebo
Phase 4

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

Resource links provided by NLM:

Further study details as provided by Radiant Research:

Primary Outcome Measures:
  • 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.

Secondary Outcome Measures:
  • Change From Baseline in Total Cholesterol, From Fasting Plasma Samples [ Time Frame: 7 weeks ]
    plasma levels of total cholesterol

  • de Novo Cholesterol Synthesis (DNC) [ Time Frame: 7 weeks ]
    Plasma DNC will be measured following the isotope infusion of deuterated water, expressed as %.

  • Cholesterol Efflux Rate (Ra Cholesterol) [ Time Frame: 7 weeks ]
    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 ]
    Change from baseline in plasma triglycerides, measured in fasting blood samples

  • Low-density Lipoprotein (LDL); [ Time Frame: 7 weeks ]
    Change from baseline in plasma low-density lipoprotein(LDL), measured in fasting blood samples

  • High-density Lipoprotein (HDL) [ Time Frame: 7 weeks ]
    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.

Ages Eligible for Study:   21 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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
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Please refer to this study by its identifier: NCT00701727

United States, Illinois
Radiant Research
Chicago, Illinois, United States, 60610
Sponsors and Collaborators
Radiant Research
Principal Investigator: Michael H Davidson, Md. FACC Radiant Research
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Michael H. Davidson, MD, FACC, Radiant Research 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

Keywords provided by Radiant Research:
metabolic diseases
metabolic disorder
lipid metabolism disorders

Additional relevant MeSH terms:
Lipid Metabolism Disorders
Metabolic Diseases
Anticholesteremic Agents
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents processed this record on April 28, 2017