Ezetimibe Reverse Cholesterol Transport (RCT) Pilot Study
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.
|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|
- 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:
- The composition of fecal neutral and acidic sterols will be measured as % of total.
- The excretion rate of fecal neutral and acidic sterols will be measured as mg/day.
- The isotopic enrichment of both fecal neutral and acidic sterols will be measured as atomic percent excess (% APE).
- Fecal isotope excretion, or recovery, of plasma-derived cholesterol will be calculated as %/day.
- 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
|Study Start Date:||June 2008|
|Study Completion Date:||March 2009|
|Primary Completion Date:||March 2009 (Final data collection date for primary outcome measure)|
ezetimibe (10mg/day)for 7 weeks
1 tablet,10mg, once a day, for 7 weeks
Placebo Comparator: 2
1 tablet, once a day, for 7 weeks
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.