Ezetimibe Reverse Cholesterol Transport (RCT) Pilot Study
Condition: Hypercholesterolemia
MeSH terms: Hypercholesterolemia
Intervention: ezetimibe; Placebo
Intervention description: 1 tablet,10mg, once a day, for 7 weeks; 1 tablet, once a day, for 7 weeks
Intervention MeSH terms: Ezetimibe
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: All
Minimum age: 21 Years
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: metabolic diseases; metabolic disorder; dyslipidemias; lipid metabolism disorders

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.
    

Eligibility 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