Alirocumab and Reverse Cholesterol Transport
Condition: Atherosclerosis; Coronary Heart Disease
MeSH terms: Heart Diseases; Atherosclerosis; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia
Study type: Interventional
Phase: Phase 1

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.
    

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.
    

Intervention name(s): Alirocumab; Placebos
Intervention type(s): Drug; Drug
Intervention description(s): 150 mg SQ every 2 weeks; Placebo injections SQ every 2 weeks
Other intervention name(s): Praluent; Placebo
Intervention MeSH terms: Alirocumab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science