<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03014830</url>
  </required_header>
  <id_info>
    <org_study_id>201612021</org_study_id>
    <nct_id>NCT03014830</nct_id>
  </id_info>
  <brief_title>Alirocumab and Reverse Cholesterol Transport</brief_title>
  <official_title>Effect of Alirocumab on Reverse Cholesterol Transport in Humans</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Washington University School of Medicine</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Alirocumab is an injectable treatment for elevated blood cholesterol. The hypothesis of this&#xD;
      study is that it also increases cholesterol excretion from the body into the stool, a process&#xD;
      sometimes called reverse cholesterol transport. A cholesterol metabolic study will be done&#xD;
      before and after 6 weeks of alirocumab treatment. If alirocumab increases reverse cholesterol&#xD;
      transport, it is possible that this action provides additional protection from cardiovascular&#xD;
      disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a single-site, randomized, placebo-controlled clinical trial in which about 24&#xD;
      subjects are expected to complete an 8-week study period. The performance site is Washington&#xD;
      University School of Medicine. Even though alirocumab is an approved drug, the investigators&#xD;
      consider this to be a phase I trial because it is a physiological study in which the primary&#xD;
      endpoint is change in fecal cholesterol excretion and measures of reverse cholesterol&#xD;
      transport. It is not a treatment protocol and uses healthy subjects.&#xD;
&#xD;
      Subjects with greater than ideal cholesterol but not taking cholesterol lowering drugs will&#xD;
      be studied. All receive whole body cholesterol metabolism tests before and after treatment&#xD;
      for 6 weeks with either alirocumab or placebo. Each test takes 2 weeks. On the first day the&#xD;
      subjects receive about 35 mg cholesterol-d7 intravenously and blood samples are obtained in&#xD;
      order to measure cholesterol turnover rate, pool size, esterification rate, transfer from HDL&#xD;
      to LDL and removal from the plasma compartment. Fecal cholesterol excretion and related&#xD;
      parameters are measured on days 13 and 14 after a relative steady-state is obtained. During&#xD;
      this time the subjects consume a metabolic kitchen diet controlled in cholesterol and&#xD;
      phytosterol content and consume oral tracer capsules consisting of cholesterol-d5 and&#xD;
      sitostanol-d4. Plasma and stool samples are analyzed by gas chromatography/tandem mass&#xD;
      spectrometry to determine daily percent cholesterol excretion from rapidly-mixing body&#xD;
      cholesterol pools, fecal cholesterol mass and percent cholesterol absorption. The cholesterol&#xD;
      metabolic test is repeated on day 43 and final measurements are made on day 57. Treatment&#xD;
      effect, defined as the difference between active and placebo treatments is then calculated.&#xD;
      Based on animal data it is expected that alirocumab will increase the efficiency of&#xD;
      cholesterol excretion from body pools and the rate of removal of cholesterol ester from&#xD;
      plasma.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 1, 2017</start_date>
  <completion_date type="Actual">July 30, 2018</completion_date>
  <primary_completion_date type="Actual">June 4, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in percent cholesterol excretion per day.</measure>
    <time_frame>Measurements made on days 13-15 (baseline) and days 55-57 (on treatment).</time_frame>
    <description>Percent cholesterol excretion per day is defined as the percent of endogenous rapidly-mixing cholesterol pools excreted per day into the stool.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline in removal rate of esterified cholesterol from plasma per day.</measure>
    <time_frame>Measurements made on days 1-3 (baseline) and days 43-45 (on treatment).</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in LDL cholesterol</measure>
    <time_frame>Measurements made on day 15 (baseline) and day 57 (on treatment).</time_frame>
    <description>Reduction in LDL with alirocumab treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in percent cholesterol absorption</measure>
    <time_frame>Measurements made on days 13-15 (baseline) and days 55-57 (on treatment).</time_frame>
    <description>Percent cholesterol absorption is defined as the percent of intestinal cholesterol absorbed into the body.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Atherosclerosis</condition>
  <condition>Coronary Heart Disease</condition>
  <arm_group>
    <arm_group_label>Alirocumab</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects will receive alirocumab for 6 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebos</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects will receive placebo for 6 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Alirocumab</intervention_name>
    <description>150 mg SQ every 2 weeks</description>
    <arm_group_label>Alirocumab</arm_group_label>
    <other_name>Praluent</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebos</intervention_name>
    <description>Placebo injections SQ every 2 weeks</description>
    <arm_group_label>Placebos</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy or with stable medical or surgical illnesses&#xD;
&#xD;
          -  LDL&gt;100 mg/dl.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Triglycerides&gt;250&#xD;
&#xD;
          -  Taking drugs affecting lipid metabolism&#xD;
&#xD;
          -  Elevated liver function tests&#xD;
&#xD;
          -  Diabetes mellitus&#xD;
&#xD;
          -  A1c 6.5% or greater&#xD;
&#xD;
          -  Pregnant&#xD;
&#xD;
          -  Breastfeeding&#xD;
&#xD;
          -  Desire for conception in either sex.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Richard E Ostlund, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Washington University School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>December 6, 2016</study_first_submitted>
  <study_first_submitted_qc>January 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 9, 2017</study_first_posted>
  <last_update_submitted>November 5, 2018</last_update_submitted>
  <last_update_submitted_qc>November 5, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 7, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Diseases</mesh_term>
    <mesh_term>Atherosclerosis</mesh_term>
    <mesh_term>Coronary Disease</mesh_term>
    <mesh_term>Coronary Artery Disease</mesh_term>
    <mesh_term>Myocardial Ischemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alirocumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>No plans to share individual data.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03014830
org study id: 201612021
nct id: NCT03014830
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change from baseline in percent cholesterol excretion per day.
time frame: Measurements made on days 13-15 (baseline) and days 55-57 (on treatment).
description: Percent cholesterol excretion per day is defined as the percent of endogenous rapidly-mixing cholesterol pools excreted per day into the stool.
measure: 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).
description: 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.
measure: Change from baseline in LDL cholesterol
time frame: Measurements made on day 15 (baseline) and day 57 (on treatment).
description: Reduction in LDL with alirocumab treatment.
measure: Change from baseline in percent cholesterol absorption
time frame: Measurements made on days 13-15 (baseline) and days 55-57 (on treatment).
description: Percent cholesterol absorption is defined as the percent of intestinal cholesterol absorbed into the body.
arm group label: Alirocumab
arm group type: Active Comparator
description: Subjects will receive alirocumab for 6 weeks.
arm group label: Placebos
arm group type: Placebo Comparator
description: Subjects will receive placebo for 6 weeks.
intervention type: Drug
intervention name: Alirocumab
description: 150 mg SQ every 2 weeks
arm group label: Alirocumab
other name: Praluent
intervention type: Drug
intervention name: Placebos
description: Placebo injections SQ every 2 weeks
arm group label: Placebos
other name: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Richard E Ostlund, MD
role: Principal Investigator
affiliation: Washington University School of Medicine
facility: 
country: United States
responsible party type: Sponsor
mesh term: Heart Diseases
mesh term: Atherosclerosis
mesh term: Coronary Disease
mesh term: Coronary Artery Disease
mesh term: Myocardial Ischemia
mesh term: Alirocumab
sharing ipd: No
ipd description: No plans to share individual data.