Alirocumab and Reverse Cholesterol Transport
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|ClinicalTrials.gov Identifier: NCT03014830|
Recruitment Status : Completed
First Posted : January 9, 2017
Last Update Posted : November 7, 2018
|Condition or disease||Intervention/treatment||Phase|
|Atherosclerosis Coronary Heart Disease||Drug: Alirocumab Drug: Placebos||Phase 1|
This study is a single-site, randomized, placebo-controlled clinical trial in which about 24 subjects are expected to complete an 8-week study period. The performance site is Washington University School of Medicine. Even though alirocumab is an approved drug, the investigators consider this to be a phase I trial because it is a physiological study in which the primary endpoint is change in fecal cholesterol excretion and measures of reverse cholesterol transport. It is not a treatment protocol and uses healthy subjects.
Subjects with greater than ideal cholesterol but not taking cholesterol lowering drugs will be studied. All receive whole body cholesterol metabolism tests before and after treatment for 6 weeks with either alirocumab or placebo. Each test takes 2 weeks. On the first day the subjects receive about 35 mg cholesterol-d7 intravenously and blood samples are obtained in order to measure cholesterol turnover rate, pool size, esterification rate, transfer from HDL to LDL and removal from the plasma compartment. Fecal cholesterol excretion and related parameters are measured on days 13 and 14 after a relative steady-state is obtained. During this time the subjects consume a metabolic kitchen diet controlled in cholesterol and phytosterol content and consume oral tracer capsules consisting of cholesterol-d5 and sitostanol-d4. Plasma and stool samples are analyzed by gas chromatography/tandem mass spectrometry to determine daily percent cholesterol excretion from rapidly-mixing body cholesterol pools, fecal cholesterol mass and percent cholesterol absorption. The cholesterol metabolic test is repeated on day 43 and final measurements are made on day 57. Treatment effect, defined as the difference between active and placebo treatments is then calculated. Based on animal data it is expected that alirocumab will increase the efficiency of cholesterol excretion from body pools and the rate of removal of cholesterol ester from plasma.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||28 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Primary Purpose:||Basic Science|
|Official Title:||Effect of Alirocumab on Reverse Cholesterol Transport in Humans|
|Actual Study Start Date :||June 1, 2017|
|Actual Primary Completion Date :||June 4, 2018|
|Actual Study Completion Date :||July 30, 2018|
Active Comparator: Alirocumab
Subjects will receive alirocumab for 6 weeks.
150 mg SQ every 2 weeks
Other Name: Praluent
Placebo Comparator: Placebos
Subjects will receive placebo for 6 weeks.
Placebo injections SQ every 2 weeks
Other Name: Placebo
- Change from baseline in percent cholesterol excretion per day. [ Time Frame: Measurements made on days 13-15 (baseline) and days 55-57 (on treatment). ]Percent cholesterol excretion per day is defined as the percent of endogenous rapidly-mixing cholesterol pools excreted per day into the stool.
- Change from baseline in removal rate of esterified cholesterol from plasma per day. [ Time Frame: Measurements made on days 1-3 (baseline) and days 43-45 (on treatment). ]The removal rate of esterified cholesterol from plasma per day is defined as fractional removal rate of esterified cholesterol from the plasma in pools/day.
- Change from baseline in LDL cholesterol [ Time Frame: Measurements made on day 15 (baseline) and day 57 (on treatment). ]Reduction in LDL with alirocumab treatment.
- Change from baseline in percent cholesterol absorption [ Time Frame: Measurements made on days 13-15 (baseline) and days 55-57 (on treatment). ]Percent cholesterol absorption is defined as the percent of intestinal cholesterol absorbed into the body.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03014830
|United States, Missouri|
|Washington University School of Medicine|
|Saint Louis, Missouri, United States, 63110|
|Principal Investigator:||Richard E Ostlund, MD||Washington University School of Medicine|