Phytosterols, Ezetimibe, and Cholesterol Metabolism
Condition: Hypercholesterolemia; Coronary Heart Disease
MeSH terms: Heart Diseases; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Hypercholesterolemia
Study type: Interventional
Phase: Early Phase 1

Summary: 
      Phytosterols and ezetimibe each reduce intestinal cholesterol absorption by 30-55% but appear
      to have different mechanisms of action. The investigators' hypothesis is that phytosterols
      and ezetimibe given together will block cholesterol absorption in an additive fashion. In a
      randomized, placebo-controlled crossover trial the effects of placebo, ezetimibe treatment
      and ezetimibe plus phytosterol treatment will be measured.
    

Detailed description: 
      The investigators will perform a randomized, placebo-controlled crossover feeding study in 25
      subjects with greater than ideal levels of LDL cholesterol who do not require
      anti-cholesterol drug treatment. Subjects will consume a baseline diet provided by a feeding
      center that is deficient in phytosterols for three periods of 21 days separated by 7-day
      washout periods. Treatments will be given in random order During period B placebo
      phytosterols and placebo ezetimibe will be given; during period C placebo phytosterols and
      active ezetimibe will be given; during period A active phytosterols and active ezetimibe will
      be given. Study endpoints are fecal cholesterol excretion and percent cholesterol absorption
      determined by gas chromatography/mass spectrometry and circulating LDL cholesterol.
    

Intervention name(s): Ezetimibe; Phytosterols + ezetimibe; Placebo
Intervention type(s): Drug; Other; Other
Intervention description(s): Subjects will undergo three diet periods of 21 days each separated by 7 day washouts. Food will be supplied by a metabolic kitchen and will consist of a phytosterol-deficient baseline diet. During each period subjects will receive either phytosterol esters or placebo and ezetimibe or placebo.; Subjects will undergo three diet periods of 21 days each separated by 7 day washouts. Food will be supplied by a metabolic kitchen and will consist of a phytosterol-deficient baseline diet. During each period subjects will receive either phytosterol esters or placebo and ezetimibe or placebo.
Other intervention name(s): C; A; B
Intervention MeSH terms: Ezetimibe
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: This is a randomized, crossover design. There are three periods of 21 days separated by two 7 day washouts. All subjects eat a controlled low-phytosterol diet for each of the three periods. During period B placebo phytosterols and placebo ezetimibe are given. During period C phytosterol placebo and active ezetimibe are given. During period A active phytosterols and active ezetimibe are given. Periods are assigned in random order as described in Arms below.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Phytosterols; Ezetimibe; Cholesterol Excretion; Cholesterol Absorption; Diet; Mass Spectrometry; Deuterium