Ezetimibe Reverse Cholesterol Transport (RCT) Pilot Study
This study has been completed.
Sponsor:
Radiant Research
Information provided by:
Radiant Research
ClinicalTrials.gov Identifier:
NCT00701727
First received: June 17, 2008
Last updated: March 14, 2011
Last verified: March 2011
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Purpose
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 |
|---|---|---|
|
Hypercholesterolemia |
Drug: ezetimibe Drug: Placebo |
Phase 4 |
| Study Type: | Interventional |
| 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 |
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 ] [ 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.
Secondary Outcome Measures:
- 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
| 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.
Eligibility| Ages Eligible for Study: | 21 Years to 75 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
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
Contacts and Locations More Information
No publications provided
| Responsible Party: | Michael H. Davidson, MD, FACC, Radiant Research |
| ClinicalTrials.gov 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 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Radiant Research:
|
metabolic diseases metabolic disorder dyslipidemias lipid metabolism disorders |
Additional relevant MeSH terms:
|
Hypercholesterolemia Hyperlipidemias Dyslipidemias Lipid Metabolism Disorders Metabolic Diseases Ezetimibe Anticholesteremic Agents |
Hypolipidemic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Lipid Regulating Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on May 16, 2013