<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/NCT02223429</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00044782</org_study_id>
    <secondary_id>R21HD078778</secondary_id>
    <nct_id>NCT02223429</nct_id>
  </id_info>
  <brief_title>Neurobiological Bases of Paternal Nurturance</brief_title>
  <official_title>Biological Bases of Individual Variation in Paternal Nurturance</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>James K. Rilling, PhD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Emory University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The overall goal of this project is to identify the genetic, hormonal, and neurobiological&#xD;
      influences on paternal nurturing behavior and to determine if fathers' neural responses to&#xD;
      infants can be modulated by neuropeptides known to play a role in parenting in experimental&#xD;
      animal models.&#xD;
&#xD;
      The aim is to determine if pharmacological manipulation of central oxytocin (OT) and&#xD;
      vasopressin (AVP) levels influences the neural response to viewing pictures of one's own&#xD;
      infant or to hearing cry stimuli. In a double-blind procedure, fathers with 1-3 year old&#xD;
      children will be scanned on two separate occasions; once under the influence of OT/AVP and&#xD;
      once under the influence of placebo. Fathers will be randomized to either OT or AVP, and&#xD;
      order of administration of drug and placebo will counterbalanced across subjects. Fathers&#xD;
      will be scanned while viewing pictures of their own and an unknown child and while listening&#xD;
      to unknown infant cry stimuli.&#xD;
&#xD;
      The investigators hypothesize:&#xD;
&#xD;
        -  OT will augment the ventral tegmental area (VTA), ventral striatum and medial&#xD;
           orbitofrontal cortex (mOFC) response to viewing pictures of one's own child, and will&#xD;
           augment the primary auditory cortex (AI) response of fathers to infant cries.&#xD;
&#xD;
        -  AVP will augment the lateral septum response to viewing own child pictures.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      30 fathers of children aged 1-3 will participate in two functional imaging sequence (fMRI)&#xD;
      sessions, once under the influence of OT/AVP, and once under the influence of placebo.&#xD;
      Fathers will be restricted to men who are living with their biological child and an adult&#xD;
      partner (male or female) that they are in a committed relationship with. All fathers will&#xD;
      receive two fMRI scans on two different occasions, separated by 2-10 days. 15 fathers will be&#xD;
      randomized to intranasal OT, the other 15 will be randomized to intranasal AVP. Within each&#xD;
      drug group, the order of administration of drug and placebo will counterbalanced across&#xD;
      subjects, such that 15 will receive OT/AVP first, and 15 will receive OT/AVP second. During&#xD;
      the fMRI scans, fathers will view pictures of their own and unknown children, as well as&#xD;
      unknown adults. Afterwards, while still in the scanner, they will listen to infant cry and&#xD;
      control stimuli. After exiting the scanner, fathers will again listen to the cry stimuli and&#xD;
      will rate their emotional reaction to the cry stimuli on the following dimensions using a 7&#xD;
      point likert scale: irritated, sympathetic, alarmed, angry, upset, compassionate, distressed,&#xD;
      annoyed, and tender.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">February 2016</completion_date>
  <primary_completion_date type="Actual">February 2016</primary_completion_date>
  <phase>N/A</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>Basic Science</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean Percent Signal Change in Ventral Tegmental Area (VTA)</measure>
    <time_frame>Baseline, Visit 2 (Up to 10 days)</time_frame>
    <description>The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI). Changes will be assessed in the OT group only per protocol.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean Percent Signal Change in Right Ventral Striatum</measure>
    <time_frame>Baseline, Visit 2 (Up to 10 days)</time_frame>
    <description>The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI). Changes will be assessed in the OT group only per protocol.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean Percent Signal Change in Right Medial Orbitofrontal Cortex</measure>
    <time_frame>Baseline, Visit 2 (Up to 10 days)</time_frame>
    <description>The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI). Changes will be assessed in the OT group only per protocol.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean Percent Signal Change in Caudate Nucleus</measure>
    <time_frame>Baseline, Visit 2 (Up to 10 days)</time_frame>
    <description>The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean Percent Signal Change in the Visual Cortex</measure>
    <time_frame>Baseline, Visit 2 (Up to 10 days)</time_frame>
    <description>The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean Percent Signal Change in the Anterior Cingulate Cortex</measure>
    <time_frame>Baseline, Visit 2 (Up to 10 days)</time_frame>
    <description>The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Plasma Levels of Vasopressin (AVP)</measure>
    <time_frame>Baseline, Visit 2 (Up to 10 days)</time_frame>
    <description>Peripheral levels of AVP will be assessed via assay of plasma collected.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Plasma Levels of Oxytocin (OT)</measure>
    <time_frame>Baseline, Visit 2 (Up to 10 days)</time_frame>
    <description>Peripheral levels of OT will be assessed via assay of plasma collected.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in Cry Rating Scores Between OT and Placebo</measure>
    <time_frame>Baseline, Visit 2 (Up to 10 days)</time_frame>
    <description>The effect of the drug will be assessed by analyzing the differences between ratings of infant cries under OT and placebo treatment on a 7-point likert scale. Sixteen adjectives will be used to describe two different cries. Participants will rate each cry from 1-7 where one represents &quot;not at all&quot; and 7 represents &quot;extremely&quot;. Difference is defined as OT minus placebo scores.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in Cry Rating Scores Between AVP and Placebo</measure>
    <time_frame>Baseline, Visit 2 (Up to 10 days)</time_frame>
    <description>The effect of the drug will be assessed by analyzing the differences between ratings of infant cries under AVP and placebo treatment on a 7-point likert scale. Sixteen adjectives will be used to describe two different cries. Participants will rate each cry from 1-7 where one represents &quot;not at all&quot; and 7 represents &quot;extremely&quot;. Difference is defined as AVP minus placebo scores.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Percent Signal Change in Primary Auditory Cortex</measure>
    <time_frame>Baseline, Visit 2 (Up to 10 days)</time_frame>
    <description>The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI). Changes will be assessed in the OT group only per protocol.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Percent Signal Change in Right Lateral Septum</measure>
    <time_frame>Baseline, Visit 2 (Up to 10 days)</time_frame>
    <description>The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between AVP treatment and placebo treatments (AVP-PL) from functional magnetic resonance imaging (fMRI). Changes will be assessed in the AVP group only per protocol.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">35</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>OT + placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The OT + placebo group will self-administer no more than 1 ml solution of oxytocin or placebo in each nostril; five (5) sprays per each nostril, for a total of ten (10) sprays. The order of administration of drug and placebo will counterbalanced across subjects, such that half will receive OT first, and half will receive OT second.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AVP + placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The AVP + placebo group will self-administer no more than 1 ml solution of vasopressin or placebo in each nostril; five (5) sprays per each nostril, for a total of ten (10) sprays. The order of administration of drug and placebo will counterbalanced across subjects, such that half will receive AVP first, and half will receive AVP second.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxytocin</intervention_name>
    <description>1 ml solution in each nostril; five (5) sprays per each nostril, for a total of ten (10) sprays</description>
    <arm_group_label>OT + placebo</arm_group_label>
    <other_name>Pitocin</other_name>
    <other_name>Syntocinon</other_name>
    <other_name>OT</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vasopressin</intervention_name>
    <description>1 ml solution in each nostril; five (5) sprays per each nostril, for a total of ten (10) sprays</description>
    <arm_group_label>AVP + placebo</arm_group_label>
    <other_name>Argipressin</other_name>
    <other_name>Arginine vasopressin (AVP)</other_name>
    <other_name>Antidiuretic hormone (ADH)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>1 ml solution in each nostril; five (5) sprays per each nostril, for a total of ten (10) sprays</description>
    <arm_group_label>AVP + placebo</arm_group_label>
    <arm_group_label>OT + placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  above 18&#xD;
&#xD;
          -  biological fathers of 1-3 year old infants who are currently cohabitating with the&#xD;
             child's mother&#xD;
&#xD;
          -  normal or corrected-to-normal vision of 20/40&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  current or past history of mental illness&#xD;
&#xD;
          -  active medical or neurological disorder&#xD;
&#xD;
          -  current or past history of alcohol or drug dependence&#xD;
&#xD;
          -  claustrophobic (at the discretion of the PI with subject consultation)&#xD;
&#xD;
          -  history of seizures or other neurological disorder&#xD;
&#xD;
          -  history of hypertension, cardiovascular disease, nephritis, diabetes or other&#xD;
             endocrine diseases or malignancy&#xD;
&#xD;
          -  ferrous metal in any part of the body&#xD;
&#xD;
          -  history of asthma or migraine headaches (can be included at the discretion of the&#xD;
             study physician or nurse practitioner if episodes are infrequent and no active&#xD;
             problems at time of study, not medicated)&#xD;
&#xD;
          -  history of head trauma or psychiatric illness, as well as those who are receiving or&#xD;
             have received over the past year, medication with known psychoactive effects (included&#xD;
             at the discretion of the PI as these are exclusion criteria due to data quality&#xD;
             concerns and not safety concerns; head trauma should be minimal enough deemed by the&#xD;
             PI)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>James K Rilling, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emory University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Emory University Hospital</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30307</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University 1462 Clifton Rd</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://anthropology.emory.edu/home/people/faculty/rilling.html</url>
    <description>Related Info</description>
  </link>
  <reference>
    <citation>Hamann S, Herman RA, Nolan CL, Wallen K. Men and women differ in amygdala response to visual sexual stimuli. Nat Neurosci. 2004 Apr;7(4):411-6. doi: 10.1038/nn1208. Epub 2004 Mar 7.</citation>
    <PMID>15004563</PMID>
  </reference>
  <verification_date>April 2017</verification_date>
  <study_first_submitted>August 20, 2014</study_first_submitted>
  <study_first_submitted_qc>August 20, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 22, 2014</study_first_posted>
  <results_first_submitted>February 28, 2017</results_first_submitted>
  <results_first_submitted_qc>April 27, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">June 5, 2017</results_first_posted>
  <last_update_submitted>April 27, 2017</last_update_submitted>
  <last_update_submitted_qc>April 27, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">June 5, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Emory University</investigator_affiliation>
    <investigator_full_name>James K. Rilling, PhD</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Paternal nurturance</keyword>
  <keyword>Oxytocin</keyword>
  <keyword>Vasopressin</keyword>
  <keyword>fMRI</keyword>
  <keyword>Neurobiology</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vasopressins</mesh_term>
    <mesh_term>Arginine Vasopressin</mesh_term>
    <mesh_term>Oxytocin</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Enrollment took place from 9/29/2014 through 2/3/2016.</recruitment_details>
      <pre_assignment_details>Of the 35 participants consented for participation, 32 began the study. Three participants were lost to follow up after signing the consent form.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>OT First, Followed by Placebo</title>
          <description>Participants were randomized to receive no more than 1 ml solution of self-administered oxytocin spray in each nostril followed by no more than 1 ml solution of self-administered placebo spray in each nostril. Time between interventions was 2-10 days.</description>
        </group>
        <group group_id="P2">
          <title>Placebo First, Followed by OT</title>
          <description>Participants were randomized to receive no more than 1 ml solution of self-administered placebo spray in each nostril followed by no more than 1 ml solution of self-administered oxytocin spray in each nostril. Time between interventions was 2-10 days.</description>
        </group>
        <group group_id="P3">
          <title>AVP First, Followed by Placebo</title>
          <description>Participants were randomized to receive no more than 1 ml solution of self-administered vasopressin spray in each nostril followed by no more than 1 ml solution of self-administered placebo spray in each nostril. Time between interventions was 2-10 days.</description>
        </group>
        <group group_id="P4">
          <title>Placebo First, Followed by AVP</title>
          <description>Participants were randomized to receive no more than 1 ml solution of self-administered placebo spray in each nostril followed by no more than 1 ml solution of self-administered vasopressin spray in each nostril. Time between interventions was 2-10 days.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="8"/>
                <participants group_id="P3" count="8"/>
                <participants group_id="P4" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="8"/>
                <participants group_id="P3" count="8"/>
                <participants group_id="P4" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Only participants who completed the study were included in the baseline analysis. Among the 32 subjects who started the study, one participant did not complete MRI scanning and was not included in any data analysis.</population>
      <group_list>
        <group group_id="B1">
          <title>OT First, Followed by Placebo</title>
          <description>Participants were randomized to receive no more than 1 ml solution of self-administered oxytocin spray in each nostril followed by no more than 1 ml solution of self-administered placebo spray in each nostril. Time between interventions was 2-10 days.</description>
        </group>
        <group group_id="B2">
          <title>Placebo First, Followed by OT</title>
          <description>Participants were randomized to receive no more than 1 ml solution of self-administered placebo spray in each nostril followed by no more than 1 ml solution of self-administered oxytocin spray in each nostril. Time between interventions was 2-10 days.</description>
        </group>
        <group group_id="B3">
          <title>AVP First, Followed by Placebo</title>
          <description>Participants were randomized to receive no more than 1 ml solution of self-administered vasopressin spray in each nostril followed by no more than 1 ml solution of self-administered placebo spray in each nostril. Time between interventions was 2-10 days.</description>
        </group>
        <group group_id="B4">
          <title>Placebo First, Followed by AVP</title>
          <description>Participants were randomized to receive no more than 1 ml solution of self-administered placebo spray in each nostril followed by no more than 1 ml solution of self-administered vasopressin spray in each nostril. Time between interventions was 2-10 days.</description>
        </group>
        <group group_id="B5">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="7"/>
            <count group_id="B2" value="8"/>
            <count group_id="B3" value="8"/>
            <count group_id="B4" value="8"/>
            <count group_id="B5" value="31"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="33.14" spread="4.14"/>
                    <measurement group_id="B2" value="31.88" spread="4.61"/>
                    <measurement group_id="B3" value="32.25" spread="5.75"/>
                    <measurement group_id="B4" value="34" spread="4.75"/>
                    <measurement group_id="B5" value="32.81" spread="4.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="8"/>
                    <measurement group_id="B5" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="8"/>
                    <measurement group_id="B5" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Mean Percent Signal Change in Ventral Tegmental Area (VTA)</title>
        <description>The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI). Changes will be assessed in the OT group only per protocol.</description>
        <time_frame>Baseline, Visit 2 (Up to 10 days)</time_frame>
        <population>The analysis was completed per protocol for the OT + placebo groups only.</population>
        <group_list>
          <group group_id="O1">
            <title>Oxytocin</title>
            <description>Participants were randomized to receive no more than 1 ml solution of self-administered oxytocin spray in each nostril followed by no more than 1 ml solution of self-administered placebo spray in each nostril. Time between interventions was 2-10 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants were randomized to receive no more than 1 ml solution of self-administered placebo spray in each nostril followed by no more than 1 ml solution of self-administered oxytocin spray in each nostril. Time between interventions was 2-10 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Percent Signal Change in Ventral Tegmental Area (VTA)</title>
          <description>The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI). Changes will be assessed in the OT group only per protocol.</description>
          <population>The analysis was completed per protocol for the OT + placebo groups only.</population>
          <units>Percent signal change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.54" spread="1.24"/>
                    <measurement group_id="O2" value="0.27" spread="1.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Mean Percent Signal Change in Right Ventral Striatum</title>
        <description>The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI). Changes will be assessed in the OT group only per protocol.</description>
        <time_frame>Baseline, Visit 2 (Up to 10 days)</time_frame>
        <population>The analysis was completed per protocol for the OT + placebo groups only.</population>
        <group_list>
          <group group_id="O1">
            <title>Oxytocin</title>
            <description>Participants were randomized to receive no more than 1 ml solution of self-administered oxytocin spray in each nostril followed by no more than 1 ml solution of self-administered placebo spray in each nostril. Time between interventions was 2-10 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants were randomized to receive no more than 1 ml solution of self-administered placebo spray in each nostril followed by no more than 1 ml solution of self-administered oxytocin spray in each nostril. Time between interventions was 2-10 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Percent Signal Change in Right Ventral Striatum</title>
          <description>The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI). Changes will be assessed in the OT group only per protocol.</description>
          <population>The analysis was completed per protocol for the OT + placebo groups only.</population>
          <units>Percent signal change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.28" spread="1.59"/>
                    <measurement group_id="O2" value="-0.81" spread="1.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Mean Percent Signal Change in Right Medial Orbitofrontal Cortex</title>
        <description>The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI). Changes will be assessed in the OT group only per protocol.</description>
        <time_frame>Baseline, Visit 2 (Up to 10 days)</time_frame>
        <population>The analysis was completed per protocol for the OT + placebo groups only.</population>
        <group_list>
          <group group_id="O1">
            <title>Oxytocin</title>
            <description>Participants were randomized to receive no more than 1 ml solution of self-administered oxytocin spray in each nostril followed by no more than 1 ml solution of self-administered placebo spray in each nostril. Time between interventions was 2-10 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants were randomized to receive no more than 1 ml solution of self-administered placebo spray in each nostril followed by no more than 1 ml solution of self-administered oxytocin spray in each nostril. Time between interventions was 2-10 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Percent Signal Change in Right Medial Orbitofrontal Cortex</title>
          <description>The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI). Changes will be assessed in the OT group only per protocol.</description>
          <population>The analysis was completed per protocol for the OT + placebo groups only.</population>
          <units>Percent signal change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.22" spread="0.64"/>
                    <measurement group_id="O2" value="-0.53" spread="0.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Mean Percent Signal Change in Caudate Nucleus</title>
        <description>The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI).</description>
        <time_frame>Baseline, Visit 2 (Up to 10 days)</time_frame>
        <population>The analysis was completed per protocol for the OT + placebo groups only.</population>
        <group_list>
          <group group_id="O1">
            <title>Oxytocin</title>
            <description>Participants were randomized to receive no more than 1 ml solution of self-administered oxytocin spray in each nostril followed by no more than 1 ml solution of self-administered placebo spray in each nostril. Time between interventions was 2-10 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants were randomized to receive no more than 1 ml solution of self-administered placebo spray in each nostril followed by no more than 1 ml solution of self-administered oxytocin spray in each nostril. Time between interventions was 2-10 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Percent Signal Change in Caudate Nucleus</title>
          <description>The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI).</description>
          <population>The analysis was completed per protocol for the OT + placebo groups only.</population>
          <units>Percent signal change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.85" spread="0.92"/>
                    <measurement group_id="O2" value="-0.27" spread="0.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Mean Percent Signal Change in the Visual Cortex</title>
        <description>The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI).</description>
        <time_frame>Baseline, Visit 2 (Up to 10 days)</time_frame>
        <population>The analysis was completed per protocol for the OT + placebo groups only.</population>
        <group_list>
          <group group_id="O1">
            <title>Oxytocin</title>
            <description>Participants were randomized to receive no more than 1 ml solution of self-administered oxytocin spray in each nostril followed by no more than 1 ml solution of self-administered placebo spray in each nostril. Time between interventions was 2-10 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants were randomized to receive no more than 1 ml solution of self-administered placebo spray in each nostril followed by no more than 1 ml solution of self-administered oxytocin spray in each nostril. Time between interventions was 2-10 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Percent Signal Change in the Visual Cortex</title>
          <description>The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI).</description>
          <population>The analysis was completed per protocol for the OT + placebo groups only.</population>
          <units>Percent signal change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.83" spread="1.18"/>
                    <measurement group_id="O2" value="0.10" spread="1.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Mean Percent Signal Change in the Anterior Cingulate Cortex</title>
        <description>The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI).</description>
        <time_frame>Baseline, Visit 2 (Up to 10 days)</time_frame>
        <population>Analysis was conducted in the OT+placebo groups only.</population>
        <group_list>
          <group group_id="O1">
            <title>Oxytocin</title>
            <description>Participants were randomized to receive no more than 1 ml solution of self-administered oxytocin spray in each nostril followed by no more than 1 ml solution of self-administered placebo spray in each nostril. Time between interventions was 2-10 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants were randomized to receive no more than 1 ml solution of self-administered placebo spray in each nostril followed by no more than 1 ml solution of self-administered oxytocin spray in each nostril. Time between interventions was 2-10 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Percent Signal Change in the Anterior Cingulate Cortex</title>
          <description>The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI).</description>
          <population>Analysis was conducted in the OT+placebo groups only.</population>
          <units>Percent signal change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.27" spread="0.60"/>
                    <measurement group_id="O2" value="-0.39" spread="0.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Plasma Levels of Vasopressin (AVP)</title>
        <description>Peripheral levels of AVP will be assessed via assay of plasma collected.</description>
        <time_frame>Baseline, Visit 2 (Up to 10 days)</time_frame>
        <population>Zero participants were analyzed as AVP samples were not assayed.</population>
        <group_list>
          <group group_id="O1">
            <title>AVP + Placebo</title>
            <description>The AVP + placebo group self-administered no more than 1 ml solution of vasopressin or placebo in each nostril; five (5) sprays per each nostril, for a total of ten (10) sprays. The order of administration of drug and placebo was counterbalanced across subjects, such that half received AVP first, and half received AVP second.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Plasma Levels of Vasopressin (AVP)</title>
          <description>Peripheral levels of AVP will be assessed via assay of plasma collected.</description>
          <population>Zero participants were analyzed as AVP samples were not assayed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Plasma Levels of Oxytocin (OT)</title>
        <description>Peripheral levels of OT will be assessed via assay of plasma collected.</description>
        <time_frame>Baseline, Visit 2 (Up to 10 days)</time_frame>
        <population>Zero participants were analyzed as samples were not assayed.</population>
        <group_list>
          <group group_id="O1">
            <title>OT + Placebo Group</title>
            <description>The OT + placebo group self-administered no more than 1 ml solution of oxytocin or placebo in each nostril; five (5) sprays per each nostril, for a total of ten (10) sprays. The order of administration of drug and placebo was counterbalanced across subjects, such that half received OT first, and half received OT second.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Plasma Levels of Oxytocin (OT)</title>
          <description>Peripheral levels of OT will be assessed via assay of plasma collected.</description>
          <population>Zero participants were analyzed as samples were not assayed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Difference in Cry Rating Scores Between OT and Placebo</title>
        <description>The effect of the drug will be assessed by analyzing the differences between ratings of infant cries under OT and placebo treatment on a 7-point likert scale. Sixteen adjectives will be used to describe two different cries. Participants will rate each cry from 1-7 where one represents &quot;not at all&quot; and 7 represents &quot;extremely&quot;. Difference is defined as OT minus placebo scores.</description>
        <time_frame>Baseline, Visit 2 (Up to 10 days)</time_frame>
        <population>Of the 15 participants who were administered oxytocin in combination with placebo at any time point during the study, data were analyzed for 14 participants. One participant was excluded from the analysis due to missing data.</population>
        <group_list>
          <group group_id="O1">
            <title>Oxytocin</title>
            <description>All participants who were administered oxytocin at any time point during the study and have completed the cry rating scale.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>All participants who were administered placebo at any time point during the study and have completed the cry rating scale.</description>
          </group>
        </group_list>
        <measure>
          <title>Difference in Cry Rating Scores Between OT and Placebo</title>
          <description>The effect of the drug will be assessed by analyzing the differences between ratings of infant cries under OT and placebo treatment on a 7-point likert scale. Sixteen adjectives will be used to describe two different cries. Participants will rate each cry from 1-7 where one represents &quot;not at all&quot; and 7 represents &quot;extremely&quot;. Difference is defined as OT minus placebo scores.</description>
          <population>Of the 15 participants who were administered oxytocin in combination with placebo at any time point during the study, data were analyzed for 14 participants. One participant was excluded from the analysis due to missing data.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cry 1 Grating</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.71" spread="1.90"/>
                    <measurement group_id="O2" value="4.64" spread="1.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 1 Urgent</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.29" spread="1.94"/>
                    <measurement group_id="O2" value="4.86" spread="1.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 1 Piercing</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.29" spread="1.86"/>
                    <measurement group_id="O2" value="4.36" spread="1.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 1 Aversive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.57" spread="1.74"/>
                    <measurement group_id="O2" value="3.36" spread="1.45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 1 Compelling</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.57" spread="1.79"/>
                    <measurement group_id="O2" value="5.00" spread="1.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 1 Manipulative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.86" spread="1.92"/>
                    <measurement group_id="O2" value="2.29" spread="1.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 1 Spoiled</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.14" spread="1.10"/>
                    <measurement group_id="O2" value="2.07" spread=".92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 1 Irritated</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.07" spread="1.86"/>
                    <measurement group_id="O2" value="3.29" spread="1.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 1 Sympathetic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.71" spread="1.50"/>
                    <measurement group_id="O2" value="4.43" spread="1.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 1 Alarmed</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.21" spread="2.00"/>
                    <measurement group_id="O2" value="4.07" spread="2.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 1 Angry</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.43" spread="1.83"/>
                    <measurement group_id="O2" value="2.57" spread="1.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 1 Upset</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.07" spread="1.90"/>
                    <measurement group_id="O2" value="3.29" spread="2.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 1 Compassionate</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.86" spread="2.07"/>
                    <measurement group_id="O2" value="5.14" spread="1.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 1 Distressed</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.57" spread="2.24"/>
                    <measurement group_id="O2" value="3.64" spread="1.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 1 Annoyed</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.43" spread="1.65"/>
                    <measurement group_id="O2" value="2.43" spread="1.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 1 Tender</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.79" spread="1.63"/>
                    <measurement group_id="O2" value="3.64" spread="1.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Grating</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.43" spread="2.17"/>
                    <measurement group_id="O2" value="3.79" spread="1.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Urgent</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.93" spread="1.54"/>
                    <measurement group_id="O2" value="4.43" spread="2.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Piercing</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.71" spread="2.23"/>
                    <measurement group_id="O2" value="4.00" spread="2.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Aversive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.50" spread="1.83"/>
                    <measurement group_id="O2" value="4.07" spread="1.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Compelling</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.21" spread="1.37"/>
                    <measurement group_id="O2" value="5.14" spread="1.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Manipulative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.43" spread="2.03"/>
                    <measurement group_id="O2" value="2.36" spread="1.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Spoiled</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.00" spread="1.41"/>
                    <measurement group_id="O2" value="2.00" spread="1.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Irritated</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.21" spread="1.53"/>
                    <measurement group_id="O2" value="2.36" spread="1.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Sypmathetic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.86" spread="1.17"/>
                    <measurement group_id="O2" value="5.64" spread="1.45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Alarmed</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.36" spread="2.34"/>
                    <measurement group_id="O2" value="4.57" spread="2.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Angry</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.79" spread="1.05"/>
                    <measurement group_id="O2" value="1.79" spread=".98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Upset</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.86" spread="1.56"/>
                    <measurement group_id="O2" value="2.57" spread="1.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Compassionate</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.71" spread="1.49"/>
                    <measurement group_id="O2" value="5.43" spread="1.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Distressed</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.36" spread="2.17"/>
                    <measurement group_id="O2" value="3.86" spread="2.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Annoyed</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.00" spread="1.30"/>
                    <measurement group_id="O2" value="1.93" spread="1.44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Tender</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.50" spread="1.22"/>
                    <measurement group_id="O2" value="4.79" spread="1.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Difference in Cry Rating Scores Between AVP and Placebo</title>
        <description>The effect of the drug will be assessed by analyzing the differences between ratings of infant cries under AVP and placebo treatment on a 7-point likert scale. Sixteen adjectives will be used to describe two different cries. Participants will rate each cry from 1-7 where one represents &quot;not at all&quot; and 7 represents &quot;extremely&quot;. Difference is defined as AVP minus placebo scores.</description>
        <time_frame>Baseline, Visit 2 (Up to 10 days)</time_frame>
        <population>Analysis was completed according to protocol for all participants who were administered AVP in combination with placebo at any time point during the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Vasopressin (AVP)</title>
            <description>All participants who were administered AVP at any time point during the study and have completed the cry rating scale.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>All participants who were administered placebo at any time point during the study and have completed the cry rating scale.</description>
          </group>
        </group_list>
        <measure>
          <title>Difference in Cry Rating Scores Between AVP and Placebo</title>
          <description>The effect of the drug will be assessed by analyzing the differences between ratings of infant cries under AVP and placebo treatment on a 7-point likert scale. Sixteen adjectives will be used to describe two different cries. Participants will rate each cry from 1-7 where one represents &quot;not at all&quot; and 7 represents &quot;extremely&quot;. Difference is defined as AVP minus placebo scores.</description>
          <population>Analysis was completed according to protocol for all participants who were administered AVP in combination with placebo at any time point during the study.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cry 1 Grating</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.69" spread="1.45"/>
                    <measurement group_id="O2" value="4.06" spread="1.611"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 1 Urgent</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.44" spread="1.09"/>
                    <measurement group_id="O2" value="5.31" spread="1.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 1 Piercing</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.81" spread="1.47"/>
                    <measurement group_id="O2" value="4.19" spread="1.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 1 Aversive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.94" spread="1.48"/>
                    <measurement group_id="O2" value="3.81" spread="1.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 1 Compelling</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.56" spread="1.32"/>
                    <measurement group_id="O2" value="5.00" spread="1.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 1 Manipulative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.06" spread="1.48"/>
                    <measurement group_id="O2" value="2.69" spread="1.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 1 Spoiled</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.44" spread="1.03"/>
                    <measurement group_id="O2" value="1.94" spread="1.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 1 Irritated</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.44" spread="1.82"/>
                    <measurement group_id="O2" value="3.44" spread="1.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 1 Sympathetic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.06" spread="1.81"/>
                    <measurement group_id="O2" value="4.38" spread="2.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 1 Alarmed</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.88" spread="1.46"/>
                    <measurement group_id="O2" value="4.38" spread="1.41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 1 Angry</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.94" spread="1.44"/>
                    <measurement group_id="O2" value="1.81" spread="1.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 1 Upset</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.00" spread="1.55"/>
                    <measurement group_id="O2" value="2.63" spread="1.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 1 Compassionate</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.88" spread="1.71"/>
                    <measurement group_id="O2" value="4.94" spread="1.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 1 Distressed</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.31" spread="1.35"/>
                    <measurement group_id="O2" value="3.31" spread="1.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 1 Annoyed</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.50" spread="1.67"/>
                    <measurement group_id="O2" value="2.25" spread="1.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 1 Tender</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.00" spread="1.51"/>
                    <measurement group_id="O2" value="4.19" spread="1.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Grating</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.25" spread="1.69"/>
                    <measurement group_id="O2" value="3.38" spread="1.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Urgent</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.13" spread="1.26"/>
                    <measurement group_id="O2" value="5.25" spread="0.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Piercing</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.13" spread="1.10"/>
                    <measurement group_id="O2" value="3.56" spread="1.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Aversive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.44" spread="1.55"/>
                    <measurement group_id="O2" value="3.44" spread="1.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Compelling</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.50" spread="1.63"/>
                    <measurement group_id="O2" value="5.00" spread="0.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Manipulative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.63" spread="2.06"/>
                    <measurement group_id="O2" value="2.38" spread="1.46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Spoiled</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.19" spread="1.33"/>
                    <measurement group_id="O2" value="2.31" spread="1.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Irritated</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.13" spread="1.50"/>
                    <measurement group_id="O2" value="2.63" spread="1.46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Sypmathetic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.88" spread="1.75"/>
                    <measurement group_id="O2" value="4.94" spread="1.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Alarmed</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.31" spread="1.74"/>
                    <measurement group_id="O2" value="4.25" spread="1.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Angry</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.13" spread="1.63"/>
                    <measurement group_id="O2" value="2.00" spread="1.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Upset</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.19" spread="1.91"/>
                    <measurement group_id="O2" value="2.88" spread="1.59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Compassionate</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.88" spread="1.75"/>
                    <measurement group_id="O2" value="4.75" spread="1.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Distressed</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.06" spread="1.77"/>
                    <measurement group_id="O2" value="3.06" spread="1.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Annoyed</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.19" spread="1.68"/>
                    <measurement group_id="O2" value="1.88" spread="1.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cry 2 Tender</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.44" spread="1.10"/>
                    <measurement group_id="O2" value="4.50" spread="1.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Percent Signal Change in Primary Auditory Cortex</title>
        <description>The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI). Changes will be assessed in the OT group only per protocol.</description>
        <time_frame>Baseline, Visit 2 (Up to 10 days)</time_frame>
        <population>The analysis was completed per protocol for the OT + placebo group only.</population>
        <group_list>
          <group group_id="O1">
            <title>Oxytocin</title>
            <description>Participants were randomized to receive no more than 1 ml solution of self-administered oxytocin spray in each nostril followed by no more than 1 ml solution of self-administered placebo spray in each nostril. Time between interventions was 2-10 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants were randomized to receive no more than 1 ml solution of self-administered placebo spray in each nostril followed by no more than 1 ml solution of self-administered oxytocin spray in each nostril. Time between interventions was 2-10 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Percent Signal Change in Primary Auditory Cortex</title>
          <description>The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI). Changes will be assessed in the OT group only per protocol.</description>
          <population>The analysis was completed per protocol for the OT + placebo group only.</population>
          <units>Percent signal change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.10" spread="0.15"/>
                    <measurement group_id="O2" value="0.10" spread="0.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Percent Signal Change in Right Lateral Septum</title>
        <description>The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between AVP treatment and placebo treatments (AVP-PL) from functional magnetic resonance imaging (fMRI). Changes will be assessed in the AVP group only per protocol.</description>
        <time_frame>Baseline, Visit 2 (Up to 10 days)</time_frame>
        <population>The analysis was conducted in the AVP groups only per protocol. One person from each order of administration were excluded from the analysis due to motion issues in their imaging data.</population>
        <group_list>
          <group group_id="O1">
            <title>Vasopressin (AVP)</title>
            <description>Participants were randomized to receive no more than 1 ml solution of self-administered vasopressin spray in each nostril followed by no more than 1 ml solution of self-administered placebo spray in each nostril. Time between interventions was 2-10 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants were randomized to receive no more than 1 ml solution of self-administered placebo spray in each nostril followed by no more than 1 ml solution of self-administered vasopressin spray in each nostril. Time between interventions was 2-10 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Percent Signal Change in Right Lateral Septum</title>
          <description>The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between AVP treatment and placebo treatments (AVP-PL) from functional magnetic resonance imaging (fMRI). Changes will be assessed in the AVP group only per protocol.</description>
          <population>The analysis was conducted in the AVP groups only per protocol. One person from each order of administration were excluded from the analysis due to motion issues in their imaging data.</population>
          <units>Percent signal change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.19" spread="0.43"/>
                    <measurement group_id="O2" value="0.36" spread="0.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected throughout the duration of the study (2 years).</time_frame>
      <group_list>
        <group group_id="E1">
          <title>OT Treatment</title>
          <description>The OT group self-administered no more than 1 ml solution of oxytocin in each nostril; five (5) sprays per each nostril, for a total of ten (10) sprays.&#xD;
This group also went through the Placebo of OT treatment.</description>
        </group>
        <group group_id="E2">
          <title>AVP Treatment</title>
          <description>The AVP group self-administered no more than 1 ml solution of vasopressin in each nostril; five (5) sprays per each nostril, for a total of ten (10) sprays.&#xD;
This group also went through the Placebo of AVP treatment.</description>
        </group>
        <group group_id="E3">
          <title>Placebo of OT</title>
          <description>The placebo of OT group self-administered no more than 1 ml solution of placebo of OT in each nostril; five (5) sprays per each nostril, for a total of ten (10) sprays.&#xD;
This group also went through the OT treatment.</description>
        </group>
        <group group_id="E4">
          <title>Placebo of AVP</title>
          <description>The placebo of AVP group self-administered no more than 1 ml solution of placebo of AVP in each nostril; five (5) sprays per each nostril, for a total of ten (10) sprays.&#xD;
This group also went through the AVP treatment.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache prior to Drug Administration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Product Issues</title>
            <event_list>
              <event>
                <sub_title>Nasal Spray Strength Intolerance</sub_title>
                <description>Participants reported that the vasopressin nasal spray was too strong. The brand was subsequently changed.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Claustrophobia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>High Blood Pressure prior to Drug Administration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Plasma levels of vasopressin (AVP) and peripheral levels of oxytocin (OT) were not assayed due to lack of funding.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. James Rilling</name_or_title>
      <organization>Emory University</organization>
      <phone>404-727-3062</phone>
      <email>jrillin@emory.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02223429
org study id: IRB00044782
secondary id: R21HD078778
nct id: NCT02223429
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated device: No
The overall goal of this project is to identify the genetic, hormonal, and neurobiological
      influences on paternal nurturing behavior and to determine if fathers' neural responses to
      infants can be modulated by neuropeptides known to play a role in parenting in experimental
      animal models.

      The aim is to determine if pharmacological manipulation of central oxytocin (OT) and
      vasopressin (AVP) levels influences the neural response to viewing pictures of one's own
      infant or to hearing cry stimuli. In a double-blind procedure, fathers with 1-3 year old
      children will be scanned on two separate occasions; once under the influence of OT/AVP and
      once under the influence of placebo. Fathers will be randomized to either OT or AVP, and
      order of administration of drug and placebo will counterbalanced across subjects. Fathers
      will be scanned while viewing pictures of their own and an unknown child and while listening
      to unknown infant cry stimuli.

      The investigators hypothesize:

        -  OT will augment the ventral tegmental area (VTA), ventral striatum and medial
           orbitofrontal cortex (mOFC) response to viewing pictures of one's own child, and will
           augment the primary auditory cortex (AI) response of fathers to infant cries.

        -  AVP will augment the lateral septum response to viewing own child pictures.
30 fathers of children aged 1-3 will participate in two functional imaging sequence (fMRI)
      sessions, once under the influence of OT/AVP, and once under the influence of placebo.
      Fathers will be restricted to men who are living with their biological child and an adult
      partner (male or female) that they are in a committed relationship with. All fathers will
      receive two fMRI scans on two different occasions, separated by 2-10 days. 15 fathers will be
      randomized to intranasal OT, the other 15 will be randomized to intranasal AVP. Within each
      drug group, the order of administration of drug and placebo will counterbalanced across
      subjects, such that 15 will receive OT/AVP first, and 15 will receive OT/AVP second. During
      the fMRI scans, fathers will view pictures of their own and unknown children, as well as
      unknown adults. Afterwards, while still in the scanner, they will listen to infant cry and
      control stimuli. After exiting the scanner, fathers will again listen to the cry stimuli and
      will rate their emotional reaction to the cry stimuli on the following dimensions using a 7
      point likert scale: irritated, sympathetic, alarmed, angry, upset, compassionate, distressed,
      annoyed, and tender.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Triple (Participant, Care Provider, Investigator)
measure: Mean Percent Signal Change in Ventral Tegmental Area (VTA)
time frame: Baseline, Visit 2 (Up to 10 days)
description: The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI). Changes will be assessed in the OT group only per protocol.
measure: Mean Percent Signal Change in Right Ventral Striatum
time frame: Baseline, Visit 2 (Up to 10 days)
description: The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI). Changes will be assessed in the OT group only per protocol.
measure: Mean Percent Signal Change in Right Medial Orbitofrontal Cortex
time frame: Baseline, Visit 2 (Up to 10 days)
description: The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI). Changes will be assessed in the OT group only per protocol.
measure: Mean Percent Signal Change in Caudate Nucleus
time frame: Baseline, Visit 2 (Up to 10 days)
description: The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI).
measure: Mean Percent Signal Change in the Visual Cortex
time frame: Baseline, Visit 2 (Up to 10 days)
description: The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI).
measure: Mean Percent Signal Change in the Anterior Cingulate Cortex
time frame: Baseline, Visit 2 (Up to 10 days)
description: The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI).
measure: Change in Plasma Levels of Vasopressin (AVP)
time frame: Baseline, Visit 2 (Up to 10 days)
description: Peripheral levels of AVP will be assessed via assay of plasma collected.
measure: Change in Plasma Levels of Oxytocin (OT)
time frame: Baseline, Visit 2 (Up to 10 days)
description: Peripheral levels of OT will be assessed via assay of plasma collected.
measure: Difference in Cry Rating Scores Between OT and Placebo
time frame: Baseline, Visit 2 (Up to 10 days)
description: The effect of the drug will be assessed by analyzing the differences between ratings of infant cries under OT and placebo treatment on a 7-point likert scale. Sixteen adjectives will be used to describe two different cries. Participants will rate each cry from 1-7 where one represents "not at all" and 7 represents "extremely". Difference is defined as OT minus placebo scores.
measure: Difference in Cry Rating Scores Between AVP and Placebo
time frame: Baseline, Visit 2 (Up to 10 days)
description: The effect of the drug will be assessed by analyzing the differences between ratings of infant cries under AVP and placebo treatment on a 7-point likert scale. Sixteen adjectives will be used to describe two different cries. Participants will rate each cry from 1-7 where one represents "not at all" and 7 represents "extremely". Difference is defined as AVP minus placebo scores.
measure: Mean Percent Signal Change in Primary Auditory Cortex
time frame: Baseline, Visit 2 (Up to 10 days)
description: The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI). Changes will be assessed in the OT group only per protocol.
measure: Mean Percent Signal Change in Right Lateral Septum
time frame: Baseline, Visit 2 (Up to 10 days)
description: The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between AVP treatment and placebo treatments (AVP-PL) from functional magnetic resonance imaging (fMRI). Changes will be assessed in the AVP group only per protocol.
arm group label: OT + placebo
arm group type: Experimental
description: The OT + placebo group will self-administer no more than 1 ml solution of oxytocin or placebo in each nostril; five (5) sprays per each nostril, for a total of ten (10) sprays. The order of administration of drug and placebo will counterbalanced across subjects, such that half will receive OT first, and half will receive OT second.
arm group label: AVP + placebo
arm group type: Experimental
description: The AVP + placebo group will self-administer no more than 1 ml solution of vasopressin or placebo in each nostril; five (5) sprays per each nostril, for a total of ten (10) sprays. The order of administration of drug and placebo will counterbalanced across subjects, such that half will receive AVP first, and half will receive AVP second.
intervention type: Drug
intervention name: Oxytocin
description: 1 ml solution in each nostril; five (5) sprays per each nostril, for a total of ten (10) sprays
arm group label: OT + placebo
other name: Pitocin
other name: Syntocinon
other name: OT
intervention type: Drug
intervention name: Vasopressin
description: 1 ml solution in each nostril; five (5) sprays per each nostril, for a total of ten (10) sprays
arm group label: AVP + placebo
other name: Argipressin
other name: Arginine vasopressin (AVP)
other name: Antidiuretic hormone (ADH)
intervention type: Drug
intervention name: Placebo
description: 1 ml solution in each nostril; five (5) sprays per each nostril, for a total of ten (10) sprays
arm group label: AVP + placebo
arm group label: OT + placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: James K Rilling, Ph.D.
role: Principal Investigator
affiliation: Emory University
facility: 
facility: 
country: United States
url: http://anthropology.emory.edu/home/people/faculty/rilling.html
description: Related Info
citation: Hamann S, Herman RA, Nolan CL, Wallen K. Men and women differ in amygdala response to visual sexual stimuli. Nat Neurosci. 2004 Apr;7(4):411-6. doi: 10.1038/nn1208. Epub 2004 Mar 7.
PMID: 15004563
responsible party type: Sponsor-Investigator
investigator affiliation: Emory University
investigator full name: James K. Rilling, PhD
investigator title: Associate Professor
mesh term: Vasopressins
mesh term: Arginine Vasopressin
mesh term: Oxytocin
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Plasma levels of vasopressin (AVP) and peripheral levels of oxytocin (OT) were not assayed due to lack of funding.
point of contact: 