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Alirocumab and Reverse Cholesterol Transport

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03014830
Recruitment Status : Completed
First Posted : January 9, 2017
Last Update Posted : November 7, 2018
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Atherosclerosis Coronary Heart Disease Drug: Alirocumab Drug: Placebos Phase 1

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Allocation: Randomized
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

Resource links provided by the National Library of Medicine

Drug Information available for: Alirocumab

Arm Intervention/treatment
Active Comparator: Alirocumab
Subjects will receive alirocumab for 6 weeks.
Drug: Alirocumab
150 mg SQ every 2 weeks
Other Name: Praluent

Placebo Comparator: Placebos
Subjects will receive placebo for 6 weeks.
Drug: Placebos
Placebo injections SQ every 2 weeks
Other Name: Placebo




Primary Outcome Measures :
  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 Outcome Measures :
  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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

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


Locations
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United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
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Principal Investigator: Richard E Ostlund, MD Washington University School of Medicine
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Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT03014830    
Other Study ID Numbers: 201612021
First Posted: January 9, 2017    Key Record Dates
Last Update Posted: November 7, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No plans to share individual data.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Heart Diseases
Atherosclerosis
Coronary Disease
Coronary Artery Disease
Myocardial Ischemia
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases