<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/NCT03011645</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00070047</org_study_id>
    <secondary_id>2P01HL036587-25</secondary_id>
    <nct_id>NCT03011645</nct_id>
  </id_info>
  <brief_title>Gene-by-Stress Interactions in Intervention Studies Significance</brief_title>
  <official_title>Gene-by-Stress Interactions in Intervention Studies Significance</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Duke University</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>
      The purpose of this study is to identify gene variants that increase risk of cardiovascular&#xD;
      disease (CVD) and type 2 diabetes, particularly genes related to stress factors.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In Aim 3, 100 subjects who participated in previous studies will be recruited to test the&#xD;
      ability of a 5HTR2C agonist (lorcaserin) to increase and antagonist (ziprasidone) to reduce&#xD;
      cortisol response to mental and metabolic stress in men carrying the rs6318 C allele and&#xD;
      women in the rs6318 CC genotype of 5HTR2C. Lorcaserin is serotonin receptor agonist indicated&#xD;
      for use as a weight loss drug. Ziprasidone is an antipsychotic indicated for treatment of&#xD;
      bipolar disorder. Subjects will be treated with a single dose of each drug, 1 to 2 weeks&#xD;
      apart, followed by a mental stress test and an oral glucose tolerance test with multiple&#xD;
      blood draws. Each subject will also receive a placebo drug during one of the study visits.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Lack of participants&#xD;
  </why_stopped>
  <start_date type="Actual">May 24, 2018</start_date>
  <completion_date type="Actual">January 28, 2020</completion_date>
  <primary_completion_date type="Actual">January 28, 2020</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>Factorial Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in peak blood cortisol during the metabolic stress of an OGTT</measure>
    <time_frame>Baseline to 3-hours post OGTT</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in peak blood cortisol during the metabolic stress of a mental stress test</measure>
    <time_frame>Baseline to 3-hours post mental stress test</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area-Under-the-Curve Glucose</measure>
    <time_frame>Baseline to 2-hours post OGTT</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Matsuda Insulin Resistance Index</measure>
    <time_frame>Baseline to 2-hours post OGTT</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">7</enrollment>
  <condition>Cardiovascular Diseases</condition>
  <arm_group>
    <arm_group_label>Ziprasidone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ziprasidone 60 mg tablet by mouth, once a day for one day.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lorcaserin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Lorcaserin 20 mg tablet by mouth, once a day for one day.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Oral Tablet</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Sugar pill (in place of ziprasidone and lorcaserin) by mouth, once a day for one day.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ziprasidone</intervention_name>
    <description>Given by mouth, single dose of 60 mg.</description>
    <arm_group_label>Ziprasidone</arm_group_label>
    <other_name>Geodon</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lorcaserin</intervention_name>
    <description>Given by mouth, single dose of 20 mg.</description>
    <arm_group_label>Lorcaserin</arm_group_label>
    <other_name>Belviq</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Tablet</intervention_name>
    <description>Given by mouth, single dose.</description>
    <arm_group_label>Placebo Oral Tablet</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men and women who have been enrolled in the STRRIDE, ENHANCED, and/or REMIT studies&#xD;
             age 18 years or greater.&#xD;
&#xD;
          -  Ability and willingness to provide informed consent.&#xD;
&#xD;
          -  Individuals with specific genotypes as determined from our previous work on their&#xD;
             samples through Aim 1 of this project.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women who are known to be pregnant, intend to become pregnant, or breast-feeding will&#xD;
             be excluded. Women who are of child bearing potential (under age 55) will be informed&#xD;
             that they will need to have their urine tested for pregnancy and that they should not&#xD;
             participate in the research if they are not willing to have the Investigators provide&#xD;
             them with information on positive pregnancy test results. Subjects will be informed&#xD;
             that the pregnancy testing is not being performed for clinical purposes and that the&#xD;
             testing is not a substitute for their regular medical care if they need to know&#xD;
             whether or not they may be pregnant.&#xD;
&#xD;
          -  History of Type II diabetes mellitus.&#xD;
&#xD;
          -  History of prolonged QT interval.&#xD;
&#xD;
          -  Participation in an investigational drug trial within the last 30 days.&#xD;
&#xD;
          -  Already taking either ziprasidone or lorcaserin or any potential confounding&#xD;
             medications, for example, other weight loss medications or psychotropic medications.&#xD;
&#xD;
          -  Unwillingness to fast for at least 6 hours prior to the research study visit.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>William E Kraus, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>January 4, 2017</study_first_submitted>
  <study_first_submitted_qc>January 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 5, 2017</study_first_posted>
  <last_update_submitted>February 13, 2020</last_update_submitted>
  <last_update_submitted_qc>February 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 17, 2020</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>Cardiovascular Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ziprasidone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03011645
org study id: Pro00070047
secondary id: 2P01HL036587-25
nct id: NCT03011645
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of this study is to identify gene variants that increase risk of cardiovascular
      disease (CVD) and type 2 diabetes, particularly genes related to stress factors.
In Aim 3, 100 subjects who participated in previous studies will be recruited to test the
      ability of a 5HTR2C agonist (lorcaserin) to increase and antagonist (ziprasidone) to reduce
      cortisol response to mental and metabolic stress in men carrying the rs6318 C allele and
      women in the rs6318 CC genotype of 5HTR2C. Lorcaserin is serotonin receptor agonist indicated
      for use as a weight loss drug. Ziprasidone is an antipsychotic indicated for treatment of
      bipolar disorder. Subjects will be treated with a single dose of each drug, 1 to 2 weeks
      apart, followed by a mental stress test and an oral glucose tolerance test with multiple
      blood draws. Each subject will also receive a placebo drug during one of the study visits.
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Prevention
masking: Double (Participant, Investigator)
measure: Change in peak blood cortisol during the metabolic stress of an OGTT
time frame: Baseline to 3-hours post OGTT
measure: Change in peak blood cortisol during the metabolic stress of a mental stress test
time frame: Baseline to 3-hours post mental stress test
measure: Area-Under-the-Curve Glucose
time frame: Baseline to 2-hours post OGTT
measure: Matsuda Insulin Resistance Index
time frame: Baseline to 2-hours post OGTT
arm group label: Ziprasidone
arm group type: Active Comparator
description: Ziprasidone 60 mg tablet by mouth, once a day for one day.
arm group label: Lorcaserin
arm group type: Active Comparator
description: Lorcaserin 20 mg tablet by mouth, once a day for one day.
arm group label: Placebo Oral Tablet
arm group type: Placebo Comparator
description: Sugar pill (in place of ziprasidone and lorcaserin) by mouth, once a day for one day.
intervention type: Drug
intervention name: Ziprasidone
description: Given by mouth, single dose of 60 mg.
arm group label: Ziprasidone
other name: Geodon
intervention type: Drug
intervention name: Lorcaserin
description: Given by mouth, single dose of 20 mg.
arm group label: Lorcaserin
other name: Belviq
intervention type: Drug
intervention name: Placebo Oral Tablet
description: Given by mouth, single dose.
arm group label: Placebo Oral Tablet
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: William E Kraus, MD
role: Principal Investigator
affiliation: Duke University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Cardiovascular Diseases
mesh term: Ziprasidone
sharing ipd: No