Ezetimibe Reverse Cholesterol Transport (RCT) Pilot Study

Radiant Research

Status and phase

Completed

Phase 4

Conditions

Hypercholesterolemia

Treatments

Drug: Placebo

Drug: ezetimibe

Study type

Interventional

Funder types

Other

Identifiers

NCT00701727

Ezetimibe RCT-001

Details and patient eligibility

About

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.

Full 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.

Enrollment

31 patients

Sex

All

Ages

21 to 75 years old

Volunteers

Accepts Healthy Volunteers

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