<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/NCT04436731</url>
  </required_header>
  <id_info>
    <org_study_id>2022525</org_study_id>
    <nct_id>NCT04436731</nct_id>
  </id_info>
  <brief_title>Sex Disparities in Hypoxic Sympatholysis and Impact of Obesity</brief_title>
  <official_title>Sex Disparities in Hypoxic Sympatholysis and Impact of Obesity</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Missouri-Columbia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Missouri-Columbia</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients with sleep apnea are at increased risk of developing cardiovascular disease - with&#xD;
      women at potentially greater risk than men. Contributing mechanisms are not well understood,&#xD;
      but may be related to how women respond to low oxygen and, given over 70% of patients with&#xD;
      sleep apnea are obese, the impact of obesity. This project seeks to increase our&#xD;
      understanding of mechanisms that may contribute to sex differences in the cardiovascular&#xD;
      response to low oxygen with the hope that this knowledge will improve the efficacy of current&#xD;
      therapies and support the discovery of novel therapeutics.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 9, 2020</start_date>
  <completion_date type="Anticipated">June 30, 2025</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2025</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in forearm vascular conductance with intra-arterial drug infusion</measure>
    <time_frame>Continuous measurement of vascular conductance during infusion of each drug (final 3 min of normoxia and hypoxia).</time_frame>
    <description>Vascular conductance is an index of vascular tone and is measured using a technique called venous occlusion plethysmography.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">104</enrollment>
  <condition>Obesity</condition>
  <condition>Healthy</condition>
  <condition>Vasoconstriction</condition>
  <condition>Vasodilation</condition>
  <arm_group>
    <arm_group_label>Hypoxia Exposure</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A physician will place a catheter in the brachial artery for intra-arterial pharmacological infusions. The following drugs will be administered to each participant under room air (normoxic) and low oxygen (hypoxic) conditions: phenylephrine, dexmedetomidine, norepinephrine, phentolamine (see Interventions for details).</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Hypoxia Exposure</intervention_name>
    <description>Systemic oxygen levels will be titrated to attain hypoxemia as assessed by pulse oximetry.</description>
    <arm_group_label>Hypoxia Exposure</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Phenylephrine</intervention_name>
    <description>Phenylephrine (0.0625 mcg/dL/min) will be locally infused via brachial artery catheter during the final 3 min of normoxia and hypoxia.</description>
    <arm_group_label>Hypoxia Exposure</arm_group_label>
    <other_name>Phenylephrine Hydrochloride</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexmedetomidine</intervention_name>
    <description>Dexmedetomidine (12.5 ng/dL/min) will be locally infused via brachial artery catheter during the final 3 min of normoxia and hypoxia.</description>
    <arm_group_label>Hypoxia Exposure</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Phentolamine</intervention_name>
    <description>Phentolamine will be locally infused via brachial artery catheter for 10 min before baseline measurement (12 mcg/dL/min) and the infusion will continue at a maintenance rate (5 mcg/dL/min) during acute normoxia and hypoxia.</description>
    <arm_group_label>Hypoxia Exposure</arm_group_label>
    <other_name>Phentolamine mesylate</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Norepinephrine</intervention_name>
    <description>Regional forearm infusion at 8 ng/dL/min via brachial artery catheter during normoxia and hypoxia exposures</description>
    <arm_group_label>Hypoxia Exposure</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18-45 years of age (premenopausal)&#xD;
&#xD;
          -  Healthy weight (BMI ≥18 and ≤25 kg/m2)&#xD;
&#xD;
          -  Obese (BMI ≥30 kg/m2)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy, breastfeeding, oral hormonal contraceptive use&#xD;
&#xD;
          -  Diagnosed sleep apnea or Oxygen desaturation index &gt;10 events/hr&#xD;
&#xD;
          -  Current smoking/Nicotine use&#xD;
&#xD;
          -  Increased risk of bleeding, pro-coagulant disorders, clotting disorders,&#xD;
             anticoagulation therapy&#xD;
&#xD;
          -  Nerve/neurologic disease&#xD;
&#xD;
          -  Cardiovascular, hepatic, renal, respiratory disease&#xD;
&#xD;
          -  Blood pressure ≥140/90 mmHg&#xD;
&#xD;
          -  Diabetes, Polycystic ovarian syndrome&#xD;
&#xD;
          -  Communication barriers&#xD;
&#xD;
          -  Prescription medications, Sensitivity to lidocaine&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Jennifer L Harper, B.S.</last_name>
    <phone>573-882-2544</phone>
    <email>harperjl@missouri.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Missouri-Columbia</name>
      <address>
        <city>Columbia</city>
        <state>Missouri</state>
        <zip>65211</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jacqueline K Limberg, Ph.D.</last_name>
      <phone>573-882-2420</phone>
      <email>limbergj@missouri.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>June 8, 2020</study_first_submitted>
  <study_first_submitted_qc>June 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 18, 2020</study_first_posted>
  <last_update_submitted>April 3, 2023</last_update_submitted>
  <last_update_submitted_qc>April 3, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 5, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Missouri-Columbia</investigator_affiliation>
    <investigator_full_name>Jacqueline K Limberg, PhD</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Obesity</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Phentolamine</mesh_term>
    <mesh_term>Phenylephrine</mesh_term>
    <mesh_term>Oxymetazoline</mesh_term>
    <mesh_term>Norepinephrine</mesh_term>
    <mesh_term>Dexmedetomidine</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/NCT04436731
org study id: 2022525
nct id: NCT04436731
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Patients with sleep apnea are at increased risk of developing cardiovascular disease - with
      women at potentially greater risk than men. Contributing mechanisms are not well understood,
      but may be related to how women respond to low oxygen and, given over 70% of patients with
      sleep apnea are obese, the impact of obesity. This project seeks to increase our
      understanding of mechanisms that may contribute to sex differences in the cardiovascular
      response to low oxygen with the hope that this knowledge will improve the efficacy of current
      therapies and support the discovery of novel therapeutics.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Change in forearm vascular conductance with intra-arterial drug infusion
time frame: Continuous measurement of vascular conductance during infusion of each drug (final 3 min of normoxia and hypoxia).
description: Vascular conductance is an index of vascular tone and is measured using a technique called venous occlusion plethysmography.
arm group label: Hypoxia Exposure
arm group type: Experimental
description: A physician will place a catheter in the brachial artery for intra-arterial pharmacological infusions. The following drugs will be administered to each participant under room air (normoxic) and low oxygen (hypoxic) conditions: phenylephrine, dexmedetomidine, norepinephrine, phentolamine (see Interventions for details).
intervention type: Other
intervention name: Hypoxia Exposure
description: Systemic oxygen levels will be titrated to attain hypoxemia as assessed by pulse oximetry.
arm group label: Hypoxia Exposure
intervention type: Drug
intervention name: Phenylephrine
description: Phenylephrine (0.0625 mcg/dL/min) will be locally infused via brachial artery catheter during the final 3 min of normoxia and hypoxia.
arm group label: Hypoxia Exposure
other name: Phenylephrine Hydrochloride
intervention type: Drug
intervention name: Dexmedetomidine
description: Dexmedetomidine (12.5 ng/dL/min) will be locally infused via brachial artery catheter during the final 3 min of normoxia and hypoxia.
arm group label: Hypoxia Exposure
intervention type: Drug
intervention name: Phentolamine
description: Phentolamine will be locally infused via brachial artery catheter for 10 min before baseline measurement (12 mcg/dL/min) and the infusion will continue at a maintenance rate (5 mcg/dL/min) during acute normoxia and hypoxia.
arm group label: Hypoxia Exposure
other name: Phentolamine mesylate
intervention type: Drug
intervention name: Norepinephrine
description: Regional forearm infusion at 8 ng/dL/min via brachial artery catheter during normoxia and hypoxia exposures
arm group label: Hypoxia Exposure
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jennifer L Harper, B.S.
phone: 573-882-2544
email: harperjl@missouri.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Missouri-Columbia
investigator full name: Jacqueline K Limberg, PhD
investigator title: Assistant Professor
mesh term: Obesity
mesh term: Phentolamine
mesh term: Phenylephrine
mesh term: Oxymetazoline
mesh term: Norepinephrine
mesh term: Dexmedetomidine
sharing ipd: No