<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/NCT04435704</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00066138</org_study_id>
    <nct_id>NCT04435704</nct_id>
  </id_info>
  <brief_title>Validate a Pharmacodynamic Model of Oxytocin for Peripheral Analgesic Effects</brief_title>
  <official_title>Validate a Pharmacodynamic Model of Oxytocin for Peripheral Analgesic Effects</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>
      The goal of this study is to validate the pharmacodynamic model for pain relief from oxytocin&#xD;
      at a peripheral site by intravenous infusion targeted at different levels of the drug.&#xD;
&#xD;
      In this study healthy volunteers and people with knee arthritis so severe that they may need&#xD;
      joint replacement are recruited for a one day study. Each study participant will have an&#xD;
      intravenous(IV) catheter placed. After placement of the IV catheter oxytocin will be given by&#xD;
      IV infusion in varying amounts. The study team will perform some tests to evaluate how&#xD;
      oxytocin changes perceptions on the skin. The study team will study a painful perception by&#xD;
      placing a probe on the skin and heating it to 113 degrees Fahrenheit for 5 minutes. Each&#xD;
      study participant will score any pain that is experienced on a 0 to 10 scale.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an unblinded Pharmacokinetic/Pharmacodynamic (PK/PD) study in which oxytocin is&#xD;
      infused in increasing steps to different levels up and down in a set manner and the PD effect&#xD;
      of pain relief from each level of oxytocin determined. All study participants will receive&#xD;
      the same treatment and will not be blinded to the experimental plan, although particpants&#xD;
      will not be informed when oxytocin levels are changing.&#xD;
&#xD;
      In this study healthy people or those with knee arthritis so severe that they may need joint&#xD;
      replacement are recruited for a one day study. Participants will come to the Clinical&#xD;
      Research Unit (CRU) and one intravenous catheter (IV) will be inserted in the forearm for&#xD;
      oxytocin infusion. In this study, the oxytocin rate will be changed every 15 minutes for 7&#xD;
      times. Oxytocin will be infused by IV route and 5-min heat pain tests obtained, but instead&#xD;
      of giving oxytocin at a constant rate, the rate will be adjusted every 15 minutes to aim to&#xD;
      get the right amount at the effect site to reduce pain by 10% of the maximum, then 30%, then&#xD;
      70%, then 90%, then back down to 70%, 30%, and 10%. At the end of each of these 7 15-min&#xD;
      infusions participants will be tested for pain with heat and the study team will compare how&#xD;
      effective the calculations for the effect site are to control the amount of pain relief&#xD;
      obtained at each level.&#xD;
&#xD;
      This information will be analyzed by another group at Stanford University in the PK/PD Core&#xD;
      part of this application. Mathematics will be used to calculate how quickly oxytocin moves&#xD;
      from the blood to where it reduces pain (Part 1) and to test the accuracy of these&#xD;
      calculations (Part 2).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">June 2024</start_date>
  <completion_date type="Anticipated">January 2026</completion_date>
  <primary_completion_date type="Anticipated">January 2026</primary_completion_date>
  <phase>Phase 2</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>
    <intervention_model_description>Oxytocin will be administered by intravenous infusion at increasing and decreasing rates</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Verbal pain after heating the skin to 45 degrees Celsius</measure>
    <time_frame>Baseline at time of infusion</time_frame>
    <description>Prior to the initiation of the oxytocin infusion, the skin will be heated to 45 degrees Celsius for 5 minutes and pain 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>Verbal pain after heating the skin to 45 degrees Celsius</measure>
    <time_frame>9 minutes after baseline</time_frame>
    <description>10% dose escalation. The skin will be heated to 45 degrees Celsius for 5 minutes and pain 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>Verbal pain after heating the skin to 45 degrees Celsius</measure>
    <time_frame>24 minutes after baseline</time_frame>
    <description>30% dose escalation. The skin will be heated to 45 degrees Celsius for 5 minutes and pain 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>Verbal pain after heating the skin to 45 degrees Celsius</measure>
    <time_frame>54 minutes after baseline</time_frame>
    <description>70% dose escalation. The skin will be heated to 45 degrees Celsius for 5 minutes and pain 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>Verbal pain after heating the skin to 45 degrees Celsius</measure>
    <time_frame>69 minutes after baseline</time_frame>
    <description>90% dose escalation. The skin will be heated to 45 degrees Celsius for 5 minutes and pain 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>Verbal pain after heating the skin to 45 degrees Celsius</measure>
    <time_frame>84 minutes after baseline</time_frame>
    <description>70% dose de-escalation. The skin will be heated to 45 degrees Celsius for 5 minutes and pain 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>Verbal pain after heating the skin to 45 degrees Celsius</measure>
    <time_frame>99 minutes after baseline</time_frame>
    <description>30% dose de-escalation. The skin will be heated to 45 degrees Celsius for 5 minutes and pain 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>Verbal pain after heating the skin to 45 degrees Celsius</measure>
    <time_frame>114 minutes after baseline</time_frame>
    <description>10% dose de-escalation. The skin will be heated to 45 degrees Celsius for 5 minutes and pain 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>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">26</enrollment>
  <condition>Osteoarthritis, Knee</condition>
  <arm_group>
    <arm_group_label>Oxytocin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oxytocin will be administered at increasing and decreasing rates</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxytocin</intervention_name>
    <description>Intravenous Oxytocin</description>
    <arm_group_label>Oxytocin</arm_group_label>
    <other_name>Pitocin</other_name>
  </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, 2, or 3.&#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. For knee&#xD;
             arthritis subjects, normal blood pressure or, for those with hypertension, pressure&#xD;
             controlled with anti-hypertensives and with a resting heart rate 45-100 beats per&#xD;
             minute.&#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 4, 2020</study_first_submitted>
  <study_first_submitted_qc>June 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 17, 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>Osteoarthritis, Knee</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/NCT04435704
org study id: IRB00066138
nct id: NCT04435704
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The goal of this study is to validate the pharmacodynamic model for pain relief from oxytocin
      at a peripheral site by intravenous infusion targeted at different levels of the drug.

      In this study healthy volunteers and people with knee arthritis so severe that they may need
      joint replacement are recruited for a one day study. Each study participant will have an
      intravenous(IV) catheter placed. After placement of the IV catheter oxytocin will be given by
      IV infusion in varying amounts. The study team will perform some tests to evaluate how
      oxytocin changes perceptions on the skin. The study team will study a painful perception by
      placing a probe on the skin and heating it to 113 degrees Fahrenheit for 5 minutes. Each
      study participant will score any pain that is experienced on a 0 to 10 scale.
This is an unblinded Pharmacokinetic/Pharmacodynamic (PK/PD) study in which oxytocin is
      infused in increasing steps to different levels up and down in a set manner and the PD effect
      of pain relief from each level of oxytocin determined. All study participants will receive
      the same treatment and will not be blinded to the experimental plan, although particpants
      will not be informed when oxytocin levels are changing.

      In this study healthy people or those with knee arthritis so severe that they may need joint
      replacement are recruited for a one day study. Participants will come to the Clinical
      Research Unit (CRU) and one intravenous catheter (IV) will be inserted in the forearm for
      oxytocin infusion. In this study, the oxytocin rate will be changed every 15 minutes for 7
      times. Oxytocin will be infused by IV route and 5-min heat pain tests obtained, but instead
      of giving oxytocin at a constant rate, the rate will be adjusted every 15 minutes to aim to
      get the right amount at the effect site to reduce pain by 10% of the maximum, then 30%, then
      70%, then 90%, then back down to 70%, 30%, and 10%. At the end of each of these 7 15-min
      infusions participants will be tested for pain with heat and the study team will compare how
      effective the calculations for the effect site are to control the amount of pain relief
      obtained at each level.

      This information will be analyzed by another group at Stanford University in the PK/PD Core
      part of this application. Mathematics will be used to calculate how quickly oxytocin moves
      from the blood to where it reduces pain (Part 1) and to test the accuracy of these
      calculations (Part 2).
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Oxytocin will be administered by intravenous infusion at increasing and decreasing rates
primary purpose: Basic Science
masking: None (Open Label)
measure: Verbal pain after heating the skin to 45 degrees Celsius
time frame: Baseline at time of infusion
description: Prior to the initiation of the oxytocin infusion, the skin will be heated to 45 degrees Celsius for 5 minutes and pain 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: Verbal pain after heating the skin to 45 degrees Celsius
time frame: 9 minutes after baseline
description: 10% dose escalation. The skin will be heated to 45 degrees Celsius for 5 minutes and pain 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: Verbal pain after heating the skin to 45 degrees Celsius
time frame: 24 minutes after baseline
description: 30% dose escalation. The skin will be heated to 45 degrees Celsius for 5 minutes and pain 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: Verbal pain after heating the skin to 45 degrees Celsius
time frame: 54 minutes after baseline
description: 70% dose escalation. The skin will be heated to 45 degrees Celsius for 5 minutes and pain 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: Verbal pain after heating the skin to 45 degrees Celsius
time frame: 69 minutes after baseline
description: 90% dose escalation. The skin will be heated to 45 degrees Celsius for 5 minutes and pain 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: Verbal pain after heating the skin to 45 degrees Celsius
time frame: 84 minutes after baseline
description: 70% dose de-escalation. The skin will be heated to 45 degrees Celsius for 5 minutes and pain 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: Verbal pain after heating the skin to 45 degrees Celsius
time frame: 99 minutes after baseline
description: 30% dose de-escalation. The skin will be heated to 45 degrees Celsius for 5 minutes and pain 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: Verbal pain after heating the skin to 45 degrees Celsius
time frame: 114 minutes after baseline
description: 10% dose de-escalation. The skin will be heated to 45 degrees Celsius for 5 minutes and pain 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
arm group type: Experimental
description: Oxytocin will be administered at increasing and decreasing rates
intervention type: Drug
intervention name: Oxytocin
description: Intravenous Oxytocin
arm group label: Oxytocin
other name: Pitocin
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: Osteoarthritis, Knee
mesh term: Oxytocin
sharing ipd: No