<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/NCT04427709</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00066475</org_study_id>
    <nct_id>NCT04427709</nct_id>
  </id_info>
  <brief_title>Generate and Test the Reliability of a PD Model of OXT on Pupillary Hippus as a Measure of CNS Activity</brief_title>
  <official_title>Generate and Test the Reliability of a Pharmacodynamic Model of Oxytocin on Pupillary Hippus as a Measure of Central Nervous System Activity</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 purpose of this research is to evaluate the effects of oxytocin (naturally occurring&#xD;
      hormone) given by an intramuscular (IM; into the muscle) injection, has on your&#xD;
      parasympathetic nervous system. The parasympathetic nervous system is the part of the&#xD;
      involuntary nervous system that is sometimes called the &quot;rest and digest&quot; system; the&#xD;
      parasympathetic system conserves energy as it slightly slows the heart rate, increases&#xD;
      intestinal and gland activity, and relaxes sphincter muscles in the gastrointestinal tract.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single site study at Wake Forest School of Medicine. Healthy volunteers and&#xD;
      patients with advanced knee arthritis being seen in the Orthopedic Clinic in consultation for&#xD;
      potential total knee arthroplasty will be recruited after their doctor visit if the decision&#xD;
      is made not to perform surgery at this time.&#xD;
&#xD;
      Study participants will come to the Pain Clinical Research Unit on 2 occasions. On these&#xD;
      visits, they will receive an intramuscular (i.m.) injection of placebo or oxytocin, 25&#xD;
      micrograms (μg) (Pitocin®), obtained from the research pharmacy. The order in this cross-over&#xD;
      study will be randomized and double blind, and the studies separated by at least 48 hours.&#xD;
      Every 2.5 minutes beginning 20 minutes before injection and until 180 minutes after injection&#xD;
      oscillation in pupil diameter at low frequency (hippus) will be obtained using an infrared&#xD;
      pupilometer, in which they focus on a central point of gaze for 20 seconds. Hippus, a measure&#xD;
      of parasympathetic output to the pupil and affected by central actions of oxytocin as&#xD;
      described in preliminary data, will be calculated as the magnitude of power in the 0-0.25&#xD;
      Hertz (Hz) bin of the spectral analysis of pupil diameter, after removing blink and saccade&#xD;
      artifacts. After 180 minutes the study participant will be discharged from the Pain Clinical&#xD;
      Research Unit.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 30, 2020</start_date>
  <completion_date type="Anticipated">January 2025</completion_date>
  <primary_completion_date type="Anticipated">January 2025</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>Randomized, double blind, crossover study. Each participant will receive Oxytocin 25 micrograms and placebo via intramuscular injection</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    <masking_description>Randomization will be maintained by the research pharmacist and by an independent individual not affiliated with the data collection or outcome evaluation</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Fluctuation in Pupil Diameter (Hippus) -Pre drug administration</measure>
    <time_frame>Baseline before study drug administration</time_frame>
    <description>Magnitude of power at the dominant frequency in the Fourier transform of pupil diameter.&#xD;
One measure of coefficient of variation at each time period. It is calculated by the amount of variability in a window of time.&#xD;
Every 2.5 minutes beginning 20 minutes before the intramuscular injection of placebo or oxytocin, 25 micrograms.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Fluctuation in Pupil Diameter (Hippus) -Post drug administration</measure>
    <time_frame>up to 180 minutes after study drug administration</time_frame>
    <description>Magnitude of power at the dominant frequency in the Fourier transform of pupil diameter.&#xD;
One measure of coefficient of variation at each time period. It is calculated by the amount of variability in a window of time.&#xD;
Every 2.5 minutes for 180 after intramuscular injection of placebo or oxytocin, 25 micrograms.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">38</enrollment>
  <condition>Chronic Pain</condition>
  <condition>Osteoarthritis, Knee</condition>
  <arm_group>
    <arm_group_label>Oxytocin First, then Placebo</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Subjects in this arm will receive Intramuscular injection of Oxytocin (Pitocin®) first then placebo injection.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo, Then Oxytocin</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Subjects in this arm will receive Intramuscular placebo injection first then oxytocin injection</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxytocin</intervention_name>
    <description>Intramuscular injection of Oxytocin (Pitocin®)</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>Intramuscular placebo injection</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, 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;
&#xD;
          5. Subjects with eye pathology, eye surgery, or taking topical eye medications, or any&#xD;
             disease process that would cause motor tremors or excessive eye movements.&#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>
    <status>Recruiting</status>
    <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 9, 2020</study_first_submitted>
  <study_first_submitted_qc>June 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 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>
    <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/NCT04427709
org study id: IRB00066475
nct id: NCT04427709
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The purpose of this research is to evaluate the effects of oxytocin (naturally occurring
      hormone) given by an intramuscular (IM; into the muscle) injection, has on your
      parasympathetic nervous system. The parasympathetic nervous system is the part of the
      involuntary nervous system that is sometimes called the "rest and digest" system; the
      parasympathetic system conserves energy as it slightly slows the heart rate, increases
      intestinal and gland activity, and relaxes sphincter muscles in the gastrointestinal tract.
This is a single site study at Wake Forest School of Medicine. Healthy volunteers and
      patients with advanced knee arthritis being seen in the Orthopedic Clinic in consultation for
      potential total knee arthroplasty will be recruited after their doctor visit if the decision
      is made not to perform surgery at this time.

      Study participants will come to the Pain Clinical Research Unit on 2 occasions. On these
      visits, they will receive an intramuscular (i.m.) injection of placebo or oxytocin, 25
      micrograms (μg) (Pitocin®), obtained from the research pharmacy. The order in this cross-over
      study will be randomized and double blind, and the studies separated by at least 48 hours.
      Every 2.5 minutes beginning 20 minutes before injection and until 180 minutes after injection
      oscillation in pupil diameter at low frequency (hippus) will be obtained using an infrared
      pupilometer, in which they focus on a central point of gaze for 20 seconds. Hippus, a measure
      of parasympathetic output to the pupil and affected by central actions of oxytocin as
      described in preliminary data, will be calculated as the magnitude of power in the 0-0.25
      Hertz (Hz) bin of the spectral analysis of pupil diameter, after removing blink and saccade
      artifacts. After 180 minutes the study participant will be discharged from the Pain Clinical
      Research Unit.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Randomized, double blind, crossover study. Each participant will receive Oxytocin 25 micrograms and placebo via intramuscular injection
primary purpose: Basic Science
masking: Triple (Participant, Investigator, Outcomes Assessor)
masking description: Randomization will be maintained by the research pharmacist and by an independent individual not affiliated with the data collection or outcome evaluation
measure: Fluctuation in Pupil Diameter (Hippus) -Pre drug administration
time frame: Baseline before study drug administration
description: Magnitude of power at the dominant frequency in the Fourier transform of pupil diameter.
One measure of coefficient of variation at each time period. It is calculated by the amount of variability in a window of time.
Every 2.5 minutes beginning 20 minutes before the intramuscular injection of placebo or oxytocin, 25 micrograms.
measure: Fluctuation in Pupil Diameter (Hippus) -Post drug administration
time frame: up to 180 minutes after study drug administration
description: Magnitude of power at the dominant frequency in the Fourier transform of pupil diameter.
One measure of coefficient of variation at each time period. It is calculated by the amount of variability in a window of time.
Every 2.5 minutes for 180 after intramuscular injection of placebo or oxytocin, 25 micrograms.
arm group label: Oxytocin First, then Placebo
arm group type: Other
description: Subjects in this arm will receive Intramuscular injection of Oxytocin (Pitocin®) first then placebo injection.
arm group label: Placebo, Then Oxytocin
arm group type: Other
description: Subjects in this arm will receive Intramuscular placebo injection first then oxytocin injection
intervention type: Drug
intervention name: Oxytocin
description: Intramuscular injection of Oxytocin (Pitocin®)
arm group label: Oxytocin First, then Placebo
arm group label: Placebo, Then Oxytocin
other name: Pitocin
intervention type: Drug
intervention name: Placebo
description: Intramuscular placebo injection
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: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Osteoarthritis, Knee
mesh term: Chronic Pain
mesh term: Oxytocin
sharing ipd: No