<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/NCT03014323</url>
  </required_header>
  <id_info>
    <org_study_id>141552-specific aim 2</org_study_id>
    <nct_id>NCT03014323</nct_id>
  </id_info>
  <brief_title>Racial Differences in Vagal Control of Glucose Homeostasis, Chronic Study</brief_title>
  <acronym>RDVCGH</acronym>
  <official_title>Racial Differences in Vagal Control of Glucose Homeostasis, Chronic Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderbilt University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Vanderbilt University Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Investigators will test the hypothesis that chronic restoration of vagal nerve activity with&#xD;
      a central acetylcholinesterase inhibitor improves insulin sensitivity and reduces adipose&#xD;
      tissue oxidation in obese African American Women compared to white women.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Investigators will test the hypothesis that chronic restoration of parasympathetic nervous&#xD;
      system (PNS) activity with a central acetylcholinesterase inhibitor improves insulin&#xD;
      sensitivity and reduces adipose tissue oxidation in obese African American women (AAW)&#xD;
      compared to white women (WW). A cross-over study will be performed in matched cohorts of AAW&#xD;
      and white women subjected to chronic central acetylcholinesterase inhibition with galantamine&#xD;
      versus placebo, given orally over a 4-week period. Insulin sensitivity will be measured using&#xD;
      the gold standard hyperinsulinemic-euglycemic clamp. Adipose tissue will be obtained through&#xD;
      subcutaneous fat biopsies where F2-isoprostanes will be quantified.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    No fundings&#xD;
  </why_stopped>
  <start_date>January 2017</start_date>
  <completion_date type="Anticipated">December 2018</completion_date>
  <primary_completion_date type="Anticipated">November 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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>insulin sensitivity</measure>
    <time_frame>4 weeks</time_frame>
    <description>insulin sensitivity will be measured with hyperinsulinemic euglycemic clamps</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Insulin Sensitivity</condition>
  <condition>Oxidative Stress</condition>
  <arm_group>
    <arm_group_label>Galantamine then Placebo, WW</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 mg (1 capsule) galantamine twice a day for 4 weeks then placebo (1 capsule) twice a day for 4 weeks in white women (WW)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo then Galantamine, WW</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo (1 capsule) twice a day for 4 weeks then 4 mg (1 capsule) galantamine twice a day for 4 weeks in white women (WW)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Galantamine then Placebo, AAW</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 mg (1 capsule) galantamine twice a day for 4 weeks then placebo (1 capsule) twice a day for 4 weeks in African American Women (AAW)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo then Galantamine, AAW</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo (1 capsule) twice a day for 4 weeks then 4 mg (1 capsule) galantamine twice a day for 4 weeks African American Women (AAW)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Galantamine</intervention_name>
    <description>Galantamine 4 mg twice a day for 4 weeks</description>
    <arm_group_label>Galantamine then Placebo, AAW</arm_group_label>
    <arm_group_label>Galantamine then Placebo, WW</arm_group_label>
    <arm_group_label>Placebo then Galantamine, AAW</arm_group_label>
    <arm_group_label>Placebo then Galantamine, WW</arm_group_label>
    <other_name>Razadyne</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo 1 capsule twice a day for 4 weeks</description>
    <arm_group_label>Galantamine then Placebo, AAW</arm_group_label>
    <arm_group_label>Galantamine then Placebo, WW</arm_group_label>
    <arm_group_label>Placebo then Galantamine, AAW</arm_group_label>
    <arm_group_label>Placebo then Galantamine, WW</arm_group_label>
    <other_name>Razadyne</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          -  Female&#xD;
&#xD;
          -  African American or white (race will be self-defined, but only subjects who report&#xD;
             both parents of the same race will be included)&#xD;
&#xD;
          -  18-60 years old&#xD;
&#xD;
          -  BMI 30-45 Kg/m2&#xD;
&#xD;
          -  Not pregnant or breastfeeding&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  Pregnant or breastfeeding&#xD;
&#xD;
          -  Diabetes diagnosis (defined by the American Diabetes Association (ADA) criteria)38&#xD;
&#xD;
          -  Cardiovascular disease such as myocardial infarction within 6 months prior to&#xD;
             enrollment, presence of angina pectoris, significant arrhythmia, congestive heart&#xD;
             failure (LV hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, mitral&#xD;
             valve stenosis, aortic stenosis, or hypertrophic cardiomyopathy.&#xD;
&#xD;
          -  Arrhythmia (first-, second-, and third-degree AV block)&#xD;
&#xD;
          -  Significant weight change &gt;5% in the past 3 months&#xD;
&#xD;
          -  Impaired hepatic function (AST and/or ALT &gt;1.5X upper limit of normal range)&#xD;
&#xD;
          -  Impaired renal function (eGFR &lt;60ml/min)&#xD;
&#xD;
          -  Users of strong inhibitors of CYP3A4 or CYP2D6&#xD;
&#xD;
          -  Users of other acetylcholinesterase inhibitors such as pyridostigmine or bethanechol&#xD;
&#xD;
          -  History of alcohol or drug abuse&#xD;
&#xD;
          -  Mental conditions rendering the subject unable to understand the nature, scope, and&#xD;
             possible consequences of the study&#xD;
&#xD;
          -  Inability to comply with the protocol, e.g., uncooperative attitude, inability to&#xD;
             return for follow-up visits, and unlikelihood of completing the study&#xD;
&#xD;
          -  Steroid use within 6 weeks prior to study entry&#xD;
&#xD;
          -  Any underlying or acute disease requiring regular medication which could possibly pose&#xD;
             a threat to the subject or make implementation of the protocol or interpretation of&#xD;
             the study results difficult&#xD;
&#xD;
          -  Discretion of the investigator&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Cyndya A Shibao, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vanderbilt University Medical Center, Clinical Pharmacology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cyndya Shibao</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37027</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>January 3, 2017</study_first_submitted>
  <study_first_submitted_qc>January 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 9, 2017</study_first_posted>
  <last_update_submitted>August 9, 2018</last_update_submitted>
  <last_update_submitted_qc>August 9, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 13, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Vanderbilt University Medical Center</investigator_affiliation>
    <investigator_full_name>Cyndya Shibao</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>insulin sensitivity</keyword>
  <keyword>African American</keyword>
  <keyword>obese</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin Resistance</mesh_term>
    <mesh_term>Hypersensitivity</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Galantamine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>No sharing</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/NCT03014323
org study id: 141552-specific aim 2
nct id: NCT03014323
lead sponsor: 
has dmc: No
Investigators will test the hypothesis that chronic restoration of vagal nerve activity with
      a central acetylcholinesterase inhibitor improves insulin sensitivity and reduces adipose
      tissue oxidation in obese African American Women compared to white women.
Investigators will test the hypothesis that chronic restoration of parasympathetic nervous
      system (PNS) activity with a central acetylcholinesterase inhibitor improves insulin
      sensitivity and reduces adipose tissue oxidation in obese African American women (AAW)
      compared to white women (WW). A cross-over study will be performed in matched cohorts of AAW
      and white women subjected to chronic central acetylcholinesterase inhibition with galantamine
      versus placebo, given orally over a 4-week period. Insulin sensitivity will be measured using
      the gold standard hyperinsulinemic-euglycemic clamp. Adipose tissue will be obtained through
      subcutaneous fat biopsies where F2-isoprostanes will be quantified.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: insulin sensitivity
time frame: 4 weeks
description: insulin sensitivity will be measured with hyperinsulinemic euglycemic clamps
arm group label: Galantamine then Placebo, WW
arm group type: Experimental
description: 4 mg (1 capsule) galantamine twice a day for 4 weeks then placebo (1 capsule) twice a day for 4 weeks in white women (WW)
arm group label: Placebo then Galantamine, WW
arm group type: Placebo Comparator
description: Placebo (1 capsule) twice a day for 4 weeks then 4 mg (1 capsule) galantamine twice a day for 4 weeks in white women (WW)
arm group label: Galantamine then Placebo, AAW
arm group type: Experimental
description: 4 mg (1 capsule) galantamine twice a day for 4 weeks then placebo (1 capsule) twice a day for 4 weeks in African American Women (AAW)
arm group label: Placebo then Galantamine, AAW
arm group type: Placebo Comparator
description: Placebo (1 capsule) twice a day for 4 weeks then 4 mg (1 capsule) galantamine twice a day for 4 weeks African American Women (AAW)
intervention type: Drug
intervention name: Galantamine
description: Galantamine 4 mg twice a day for 4 weeks
arm group label: Galantamine then Placebo, AAW
arm group label: Galantamine then Placebo, WW
arm group label: Placebo then Galantamine, AAW
arm group label: Placebo then Galantamine, WW
other name: Razadyne
intervention type: Drug
intervention name: Placebo
description: Placebo 1 capsule twice a day for 4 weeks
arm group label: Galantamine then Placebo, AAW
arm group label: Galantamine then Placebo, WW
arm group label: Placebo then Galantamine, AAW
arm group label: Placebo then Galantamine, WW
other name: Razadyne
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Cyndya A Shibao, MD
role: Principal Investigator
affiliation: Vanderbilt University Medical Center, Clinical Pharmacology
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Vanderbilt University Medical Center
investigator full name: Cyndya Shibao
investigator title: Assistant Professor
mesh term: Insulin Resistance
mesh term: Hypersensitivity
mesh term: Galantamine
sharing ipd: No
ipd description: No sharing