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Completed

NCT Number: NCT03014830

Alirocumab and Reverse Cholesterol Transport

Alirocumab is an injectable treatment for elevated blood cholesterol. The hypothesis of this study is that it also increases cholesterol excretion from the body into the stool, a process sometimes called reverse cholesterol transport. A cholesterol metabolic study will be done before and after 6 weeks of alirocumab treatment. If alirocumab increases reverse cholesterol transport, it is possible that this action provides additional protection from cardiovascular disease.

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Key information

Conditions

Atherosclerosis Arterial Occlusive Diseases Arteriosclerosis Cardiovascular Diseases Coronary Disease Coronary Heart Disease Heart Diseases Myocardial Ischemia Vascular Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Healthy or with stable medical or surgical illnesses
  • LDL>100 mg/dl.

Exclusion criteria

  • Triglycerides>250
  • Taking drugs affecting lipid metabolism
  • Elevated liver function tests
  • Diabetes mellitus
  • A1c 6.5% or greater
  • Pregnant
  • Breastfeeding
  • Desire for conception in either sex.

Treatment and study plan

Alirocumab

Drug

150 mg SQ every 2 weeks

Other names: Praluent

Placebos

Drug

Placebo injections SQ every 2 weeks

Other names: Placebo

Primary outcomes

  1. 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.

  2. 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.

Secondary outcomes

  1. 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.

  2. 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.

Sponsors and collaborators

Lead sponsor

Washington University School of Medicine

Other

Registry information

Official study title

Effect of Alirocumab on Reverse Cholesterol Transport in Humans

Important dates

Study start
2017
Primary completion
2018
Study completion
2018
First posted
Jan 9, 2017
Registry last updated
Nov 7, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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