<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/NCT04433741</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00066443</org_study_id>
    <nct_id>NCT04433741</nct_id>
  </id_info>
  <brief_title>Apply the PD Model of Peripheral Oxytocin Action to a Multimodal Stimulus</brief_title>
  <official_title>Apply the Pharmacodynamic Model of Peripheral Oxytocin Action to a Multimodal Stimulus That Increases (Heat) or Decreases (Vibration) Pain Perception</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wake Forest University Health Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Wake Forest University Health Sciences</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>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a study of participants that will receive an intravenous (IV) infusion of oxytocin&#xD;
      (naturally occurring hormone that is made in the brain).&#xD;
&#xD;
      In this study healthy volunteers are recruited. Each study participant will have an IV&#xD;
      catheter placed. After placement of the IV catheter oxytocin will be given by IV infusion of&#xD;
      oxytocin or placebo (inactive solution). The investigators will perform some tests to&#xD;
      evaluate how oxytocin changes perceptions on the skin. The investigators will study a painful&#xD;
      perception by placing a probe on the skin and heating it to 116.6 degrees Fahrenheit for 30&#xD;
      seconds and a vibratory stimulus will be applied to the forearm with vibration begun at a 1&#xD;
      kHz frequency and decreased at a rate of 25 Hz/sec until the subject first perceives the&#xD;
      vibration. Each study participant will score any pain that is experienced on a 0 to 10 scale&#xD;
      and will report when the vibration is detected. Each participant will receive oxytocin and&#xD;
      placebo in a random order and will be blinded to group they are receiving.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators aim to create pharmacokinetic/pharmacodynamic (PK/PD) models for oxytocin&#xD;
      action at peripheral sites and at central sites as they relate to sensory transmission and&#xD;
      pain. This is the last of 4 studies to accomplish generation, validation, and application of&#xD;
      a PK/PD model for oxytocin in the periphery. Its goal is to apply the PK/PD model generated&#xD;
      in previous protocols and Validate a pharmacodynamic model of oxytocin for peripheral&#xD;
      analgesic effects to a more complex sensory stimulus that stimulates nerve fibers which&#xD;
      result in pain from a heat stimulus and those which reduce pain from vibration, similar to&#xD;
      brushing or rubbing an area of pain. The investigators do this because oxytocin in animals&#xD;
      affects these nerve fibers in the periphery in different ways - it increases the activity of&#xD;
      the vibration/rubbing sensitive fibers and decreases the activity of the pain fibers. As&#xD;
      such, The investigators expect that the effect of oxytocin on pain from this mixed stimulus&#xD;
      of heat and vibration will be much more pronounced than that seen with the purely painful&#xD;
      stimulus used in previous studies in this series.&#xD;
&#xD;
      This is a double-blind, crossover study in which oxytocin or placebo is infused. In this&#xD;
      study healthy people are recruited for a 2 day double-blind, crossover study. They will come&#xD;
      to the Clinical Research Unit and one intravenous catheter (IV) inserted in the forearm for&#xD;
      oxytocin or placebo infusion. Participants will be given a steady rate intravenous infusion&#xD;
      of oxytocin at a targeted dose or placebo for 30 minutes. At 5, 15, and 30 minutes after&#xD;
      starting the infusion, pain report to the 47°Celsius, 30-second stimulus alone or with ½ VT&#xD;
      vibration (randomized order) will be obtained. Participants will return at least 24 hours&#xD;
      later and receive the opposite infusion and testing.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">January 2024</start_date>
  <completion_date type="Anticipated">September 2024</completion_date>
  <primary_completion_date type="Anticipated">September 2024</primary_completion_date>
  <phase>Phase 2</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>
    <intervention_model_description>Cross over model: each participant will be randomized to receive oxytocin and placebo in a random order</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    <masking_description>Participant, outcomes assessor and investigator will be blinded to the randomization order. Research pharmacist will prepare each infusion.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Heat pain with vibration</measure>
    <time_frame>Baseline before infusion</time_frame>
    <description>Pain at the end of 30 sec of heating the skin to 47 degrees C with simultaneous vibration will be determined. Pain will be measured using a verbal Pain Scale 0-10. 0 is equivalent to NO PAIN and 10 is equivalent to WORST PAIN IMAGINABLE.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Heat pain with vibration</measure>
    <time_frame>5 minutes post infusion initiation</time_frame>
    <description>Pain at the end of 30 sec of heating the skin to 47 degrees C with simultaneous vibration will be determined. Pain will be measured using a verbal Pain Scale 0-10. 0 is equivalent to NO PAIN and 10 is equivalent to WORST PAIN IMAGINABLE.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Heat pain with vibration</measure>
    <time_frame>15 minutes post infusion initiation</time_frame>
    <description>Pain at the end of 30 sec of heating the skin to 47 degrees C with simultaneous vibration will be determined. Pain will be measured using a verbal Pain Scale 0-10. 0 is equivalent to NO PAIN and 10 is equivalent to WORST PAIN IMAGINABLE.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Heat pain with vibration</measure>
    <time_frame>30 minutes post infusion initiation</time_frame>
    <description>Pain at the end of 30 sec of heating the skin to 47 degrees C with simultaneous vibration will be determined. Pain will be measured using a verbal Pain Scale 0-10. 0 is equivalent to NO PAIN and 10 is equivalent to WORST PAIN IMAGINABLE.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Heat pain without vibration</measure>
    <time_frame>Baseline</time_frame>
    <description>Pain at the end of 30 sec of heating the skin to 47 degrees C will be determined. Pain will be measured using a verbal Pain Scale 0-10. 0 is equivalent to NO PAIN and 10 is equivalent to WORST PAIN IMAGINABLE.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heat pain without vibration</measure>
    <time_frame>5 minutes post infusion initiation</time_frame>
    <description>Pain at the end of 30 sec of heating the skin to 47 degrees C will be determined. Pain will be measured using a verbal Pain Scale 0-10. 0 is equivalent to NO PAIN and 10 is equivalent to WORST PAIN IMAGINABLE.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heat pain without vibration</measure>
    <time_frame>15 minutes post infusion initiation</time_frame>
    <description>Pain at the end of 30 sec of heating the skin to 47 degrees C will be determined. Pain will be measured using a verbal Pain Scale 0-10. 0 is equivalent to NO PAIN and 10 is equivalent to WORST PAIN IMAGINABLE.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heat pain without vibration</measure>
    <time_frame>30 minutes post infusion initiation</time_frame>
    <description>Pain at the end of 30 sec of heating the skin to 47 degrees C will be determined. Pain will be measured using a verbal Pain Scale 0-10. 0 is equivalent to NO PAIN and 10 is equivalent to WORST PAIN IMAGINABLE.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Pain, Chronic</condition>
  <arm_group>
    <arm_group_label>Oxytocin First, then Placebo</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Oxytocin administered intravenously for the first half of the study and then will receive intravenous placebo for the second half.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo, Then Oxytocin</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Placebo administered intravenously for the first half of the study and then will receive intravenous oxytocin for the second half.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxytocin</intervention_name>
    <description>Oxytocin administered intravenously</description>
    <arm_group_label>Oxytocin First, then Placebo</arm_group_label>
    <arm_group_label>Placebo, Then Oxytocin</arm_group_label>
    <other_name>Pitocin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo administered intravenously</description>
    <arm_group_label>Oxytocin First, then Placebo</arm_group_label>
    <arm_group_label>Placebo, Then Oxytocin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female &gt; 18 and &lt; 75 years of age, Body Mass Index (BMI) &lt;40.&#xD;
&#xD;
          2. Generally in good health as determined by the Principal Investigator based on prior&#xD;
             medical history, American Society of Anesthesiologists physical status 1 or 2.&#xD;
&#xD;
          3. For healthy volunteers, normal blood pressure (systolic 90-140 mmHg; diastolic 50-90&#xD;
             mmHg) resting heart rate 45-100 beats per minute) without medication.&#xD;
&#xD;
          4. Female subjects of child-bearing potential and those &lt; 1 year post-menopausal, must be&#xD;
             practicing highly effective methods of birth control such as hormonal methods (e.g.,&#xD;
             combined oral, implantable, injectable, or transdermal contraceptives), double barrier&#xD;
             methods (e.g., condoms, sponge, diaphragm, or vaginal ring plus spermicidal jellies or&#xD;
             cream), or total abstinence from heterosexual intercourse for a minimum of 1 full&#xD;
             cycle before study drug administration.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Hypersensitivity, allergy, or significant reaction to any ingredient of Pitocin®&#xD;
&#xD;
          2. Any disease, diagnosis, or condition (medical or surgical) that, in the opinion of the&#xD;
             Principal Investigator, would place the subject at increased risk (active gynecologic&#xD;
             disease in which increased tone would be detrimental e.g., uterine fibroids with&#xD;
             ongoing bleeding), compromise the subject's compliance with study procedures, or&#xD;
             compromise the quality of the data&#xD;
&#xD;
          3. Women who are pregnant (positive result for serum pregnancy test at screening visit),&#xD;
             women who are currently nursing or lactating, women that have been pregnant within 2&#xD;
             years&#xD;
&#xD;
          4. Subjects with neuropathy, chronic pain, diabetes mellitus, or taking benzodiazepines&#xD;
             or pain medications on a daily basis.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>James C Eisenach, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Wake Forest University Health Sciences</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Regina Curry, RN</last_name>
    <phone>336-716-4294</phone>
    <email>RECURRY@WAKEHEALTH.EDU</email>
  </overall_contact>
  <location>
    <facility>
      <name>Wake Forest Baptist Health</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
    <contact>
      <last_name>Regina Curry, RN</last_name>
      <phone>336-716-4294</phone>
      <email>RECURRY@WAKEHEALTH.EDU</email>
    </contact>
    <investigator>
      <last_name>James C Eisenach, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>June 11, 2020</study_first_submitted>
  <study_first_submitted_qc>June 11, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>May 2, 2023</last_update_submitted>
  <last_update_submitted_qc>May 2, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 6, 2023</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>Chronic Pain</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Oxytocin</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/NCT04433741
org study id: IRB00066443
nct id: NCT04433741
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This is a study of participants that will receive an intravenous (IV) infusion of oxytocin
      (naturally occurring hormone that is made in the brain).

      In this study healthy volunteers are recruited. Each study participant will have an IV
      catheter placed. After placement of the IV catheter oxytocin will be given by IV infusion of
      oxytocin or placebo (inactive solution). The investigators will perform some tests to
      evaluate how oxytocin changes perceptions on the skin. The investigators will study a painful
      perception by placing a probe on the skin and heating it to 116.6 degrees Fahrenheit for 30
      seconds and a vibratory stimulus will be applied to the forearm with vibration begun at a 1
      kHz frequency and decreased at a rate of 25 Hz/sec until the subject first perceives the
      vibration. Each study participant will score any pain that is experienced on a 0 to 10 scale
      and will report when the vibration is detected. Each participant will receive oxytocin and
      placebo in a random order and will be blinded to group they are receiving.
The investigators aim to create pharmacokinetic/pharmacodynamic (PK/PD) models for oxytocin
      action at peripheral sites and at central sites as they relate to sensory transmission and
      pain. This is the last of 4 studies to accomplish generation, validation, and application of
      a PK/PD model for oxytocin in the periphery. Its goal is to apply the PK/PD model generated
      in previous protocols and Validate a pharmacodynamic model of oxytocin for peripheral
      analgesic effects to a more complex sensory stimulus that stimulates nerve fibers which
      result in pain from a heat stimulus and those which reduce pain from vibration, similar to
      brushing or rubbing an area of pain. The investigators do this because oxytocin in animals
      affects these nerve fibers in the periphery in different ways - it increases the activity of
      the vibration/rubbing sensitive fibers and decreases the activity of the pain fibers. As
      such, The investigators expect that the effect of oxytocin on pain from this mixed stimulus
      of heat and vibration will be much more pronounced than that seen with the purely painful
      stimulus used in previous studies in this series.

      This is a double-blind, crossover study in which oxytocin or placebo is infused. In this
      study healthy people are recruited for a 2 day double-blind, crossover study. They will come
      to the Clinical Research Unit and one intravenous catheter (IV) inserted in the forearm for
      oxytocin or placebo infusion. Participants will be given a steady rate intravenous infusion
      of oxytocin at a targeted dose or placebo for 30 minutes. At 5, 15, and 30 minutes after
      starting the infusion, pain report to the 47°Celsius, 30-second stimulus alone or with ½ VT
      vibration (randomized order) will be obtained. Participants will return at least 24 hours
      later and receive the opposite infusion and testing.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Cross over model: each participant will be randomized to receive oxytocin and placebo in a random order
primary purpose: Basic Science
masking: Triple (Participant, Investigator, Outcomes Assessor)
masking description: Participant, outcomes assessor and investigator will be blinded to the randomization order. Research pharmacist will prepare each infusion.
measure: Heat pain with vibration
time frame: Baseline before infusion
description: Pain at the end of 30 sec of heating the skin to 47 degrees C with simultaneous vibration will be determined. Pain will be measured using a verbal Pain Scale 0-10. 0 is equivalent to NO PAIN and 10 is equivalent to WORST PAIN IMAGINABLE.
measure: Heat pain with vibration
time frame: 5 minutes post infusion initiation
description: Pain at the end of 30 sec of heating the skin to 47 degrees C with simultaneous vibration will be determined. Pain will be measured using a verbal Pain Scale 0-10. 0 is equivalent to NO PAIN and 10 is equivalent to WORST PAIN IMAGINABLE.
measure: Heat pain with vibration
time frame: 15 minutes post infusion initiation
description: Pain at the end of 30 sec of heating the skin to 47 degrees C with simultaneous vibration will be determined. Pain will be measured using a verbal Pain Scale 0-10. 0 is equivalent to NO PAIN and 10 is equivalent to WORST PAIN IMAGINABLE.
measure: Heat pain with vibration
time frame: 30 minutes post infusion initiation
description: Pain at the end of 30 sec of heating the skin to 47 degrees C with simultaneous vibration will be determined. Pain will be measured using a verbal Pain Scale 0-10. 0 is equivalent to NO PAIN and 10 is equivalent to WORST PAIN IMAGINABLE.
measure: Heat pain without vibration
time frame: Baseline
description: Pain at the end of 30 sec of heating the skin to 47 degrees C will be determined. Pain will be measured using a verbal Pain Scale 0-10. 0 is equivalent to NO PAIN and 10 is equivalent to WORST PAIN IMAGINABLE.
measure: Heat pain without vibration
time frame: 5 minutes post infusion initiation
description: Pain at the end of 30 sec of heating the skin to 47 degrees C will be determined. Pain will be measured using a verbal Pain Scale 0-10. 0 is equivalent to NO PAIN and 10 is equivalent to WORST PAIN IMAGINABLE.
measure: Heat pain without vibration
time frame: 15 minutes post infusion initiation
description: Pain at the end of 30 sec of heating the skin to 47 degrees C will be determined. Pain will be measured using a verbal Pain Scale 0-10. 0 is equivalent to NO PAIN and 10 is equivalent to WORST PAIN IMAGINABLE.
measure: Heat pain without vibration
time frame: 30 minutes post infusion initiation
description: Pain at the end of 30 sec of heating the skin to 47 degrees C will be determined. Pain will be measured using a verbal Pain Scale 0-10. 0 is equivalent to NO PAIN and 10 is equivalent to WORST PAIN IMAGINABLE.
arm group label: Oxytocin First, then Placebo
arm group type: Other
description: Oxytocin administered intravenously for the first half of the study and then will receive intravenous placebo for the second half.
arm group label: Placebo, Then Oxytocin
arm group type: Other
description: Placebo administered intravenously for the first half of the study and then will receive intravenous oxytocin for the second half.
intervention type: Drug
intervention name: Oxytocin
description: Oxytocin administered intravenously
arm group label: Oxytocin First, then Placebo
arm group label: Placebo, Then Oxytocin
other name: Pitocin
intervention type: Drug
intervention name: Placebo
description: Placebo administered intravenously
arm group label: Oxytocin First, then Placebo
arm group label: Placebo, Then Oxytocin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: James C Eisenach, MD
role: Principal Investigator
affiliation: Wake Forest University Health Sciences
last name: Regina Curry, RN
phone: 336-716-4294
email: RECURRY@WAKEHEALTH.EDU
facility: 
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Chronic Pain
mesh term: Oxytocin
sharing ipd: No