<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/NCT03016598</url>
  </required_header>
  <id_info>
    <org_study_id>NURA-014-16S</org_study_id>
    <secondary_id>1IK2CX001495-01</secondary_id>
    <nct_id>NCT03016598</nct_id>
  </id_info>
  <brief_title>Stimulant Oxytocin Study</brief_title>
  <acronym>SOS</acronym>
  <official_title>6-week Trial of Oxytocin for Co-occurring Cocaine and Opioid Use Disorders</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>VA Office of Research and Development</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>VA Office of Research and Development</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will investigate the effects of intranasal administration of oxytocin, a social&#xD;
      neuropeptide, on reducing stimulant use, enhancing therapeutic engagement, and susceptibility&#xD;
      to stress-induced relapse in Veterans with stimulant use disorders and enrolled in opioid&#xD;
      replacement therapy (ORT) program for co-occurring opioid use disorder (OUD).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      High rates of substance use disorders (SUDs) in Veterans compared to the general population&#xD;
      are heavily influenced by psychosocial factors - such as difficulty reintegrating into&#xD;
      civilian life due to avoidance of vital support systems - leading to disproportionately&#xD;
      elevated unmet addiction treatment needs. Although the gold standard for treatment for most&#xD;
      SUDs involves pharmacological interventions, there are currently no effective pharmacological&#xD;
      interventions approved by the Federal Drug Administration for stimulant users, who have the&#xD;
      most difficulty adhering to treatment programs and the most susceptibility to stress-induced&#xD;
      relapse of any SUD. Administering oxytocin, a mammalian neuropeptide, intranasally to healthy&#xD;
      controls facilitates the stress-buffering properties of social support. Oxytocin may also&#xD;
      have an independent role in mitigating the symptoms of SUDs. For example, in animal models of&#xD;
      addiction, oxytocin administration directly reduces tolerance, withdrawal effects,&#xD;
      self-administration, and stress-induced reinstatement of drug seeking for a range of&#xD;
      addictive substances. A more integrated understanding of oxytocin's distinct effects on the&#xD;
      behavior and psychology of 1) addiction, 2) sociality, and 3) stress reactivity could be the&#xD;
      key to defining oxytocin's role in SUD treatment. This study proposes to translate promising&#xD;
      preclinical and early proof-of-concept clinical results related to the anti-addiction,&#xD;
      pro-social, and stress-tempering properties of oxytocin administration in Veterans with&#xD;
      moderate-severe stimulant use disorders enrolled in a opioid replacement therapy (ORT)&#xD;
      program for co-occurring opioid use disorder (OUD) at the San Francisco VA Medical Center&#xD;
      (SFVAMC). The investigators' primary outcome is Aim 1) reduction in stimulant use, as&#xD;
      measured by stimulant positive urine drug screen. Secondarily, the investigators will focus&#xD;
      on Aim 2) improving psychosocial treatment engagement (social support) and Aim 3) mitigating&#xD;
      social stress-related relapse, targeting two important barriers to stimulant use disorder&#xD;
      recovery likely to respond to oxytocin administration.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 26, 2018</start_date>
  <completion_date type="Actual">February 14, 2020</completion_date>
  <primary_completion_date type="Actual">February 14, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Stimulant Positive Drug Screen</measure>
    <time_frame>Baseline, Visits 1-7, up to 7 weeks</time_frame>
    <description>Aim 1: To evaluate the effectiveness of intranasal oxytocin on reducing stimulant use.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Working Alliance Inventory (WAI)</measure>
    <time_frame>Visits 1 and 7, Up to 7 weeks</time_frame>
    <description>Aim 2: To evaluate the effectiveness of intranasal oxytocin on improving psychosocial treatment engagement (social support) as measured by the Working Alliance Inventory, an inventory of therapeutic alliance. The Working Alliance Inventory is a 36 question inventory. Each item is scored from 1-7, minimum = 1 and maximum = 7. Minimum total score = 36 to maximum total score = 252. Higher scores represent higher satisfaction.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart Rate in Response to Trier Social Stress Test (TSST).</measure>
    <time_frame>Visits 1 and 7, up to 7 weeks</time_frame>
    <description>Aim 3: To evaluate the effectiveness of intranasal oxytocin on reducing stress-related psycho-physiological measures in response to the Trier Social Stress Test (TSST).&#xD;
The Trier Social Stress Test is a series of tasks which predictably induce stress in participants. First, physiological states are measured at baseline. Then participants are told they must prepare a 5 minute speech for a panel of researchers, which they then present. Participants are then asked verbal arithmetic questions. Finally, this is followed by a period of 5 minute rest referred to as the 'cooldown' period.&#xD;
Heart rate was assessed at different time points during the TSST. These time point are as follows: baseline, during speech preparation, during speech presentation, during arithmetic problems, and during the cooldown period. Higher scores indicate higher stress levels.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Respiratory Rate in Response to Trier Social Stress Test (TSST).</measure>
    <time_frame>Visits 1 and 7, up to 7 weeks</time_frame>
    <description>Aim 3: To evaluate the effectiveness of intranasal oxytocin on reducing stress-related psycho-physiological measures in response to the Trier Social Stress Test (TSST).&#xD;
The Trier Social Stress Test is a series of tasks which predictably induce stress in participants. First, physiological states are measured at baseline. Then participants are told they must prepare a 5 minute speech for a panel of researchers, which they then present. Participants are then asked verbal arithmetic questions. Finally, this is followed by a period of 5 minute rest referred to as the 'cooldown' period.&#xD;
Respiratory rate was assessed at different time points during the TSST. These time point are as follows: baseline, during speech preparation, during speech presentation, during arithmetic problems, and during the cooldown period. Higher scores indicate higher stress levels.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Respiratory Sinus Arrythmia (RSA) in Response to Trier Social Stress Test (TSST).</measure>
    <time_frame>Visits 1 and 7, up to 7 weeks</time_frame>
    <description>Aim 3: To evaluate the effectiveness of intranasal oxytocin on reducing stress-related psycho-physiological measures in response to the Trier Social Stress Test (TSST).&#xD;
The Trier Social Stress Test is a series of tasks which predictably induce stress in participants. First, physiological states are measured at baseline. Then participants are told they must prepare a 5 minute speech for a panel of researchers, which they then present. Participants are then asked verbal arithmetic questions. Finally, this is followed by a period of 5 minute rest referred to as the 'cooldown' period.&#xD;
Respiratory sinus arrythmia (RSA) was assessed at different time points during the TSST. These time point are as follows: baseline, during speech preparation, during speech presentation, during arithmetic problems, and during the cooldown period. Higher scores indicate higher stress levels.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Root Mean Square of Successive Differences (RMSSD) of Heart Rate Variability in Response to Trier Social Stress Test (TSST).</measure>
    <time_frame>Visits 1 and 7, up to 7 weeks</time_frame>
    <description>Aim 3: To evaluate the effectiveness of intranasal oxytocin on reducing stress-related psycho-physiological measures in response to the Trier Social Stress Test (TSST).&#xD;
The Trier Social Stress Test is a series of tasks which predictably induce stress in participants. First, physiological states are measured at baseline. Then participants are told they must prepare a 5 minute speech for a panel of researchers, which they then present. Participants are then asked verbal arithmetic questions. Finally, this is followed by a period of 5 minute rest referred to as the 'cooldown' period.&#xD;
The root mean square of successive differences (RMSSD) were assessed at different time points during the TSST. These time point are as follows: baseline, during speech preparation, during speech presentation, during arithmetic problems, and during the cooldown period. Higher scores indicate higher stress levels. Calculated by measuring each successive time difference between heartbeats in ms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Self-reported Stimulant Craving</measure>
    <time_frame>Visits 1 and 7, Up to 7 weeks</time_frame>
    <description>Aim 4: To evaluate the effectiveness of intranasal oxytocin on reducing stimulant craving in response the Trier Social Stress Test (TSST).&#xD;
The Cocaine Craving Questionnaire (CCQ) (brief) was modified to include all stimulants and administered. The CCQ is a 10-item questionnaire, with each item ranking on a scale of 1-7. 1 indicates 'Strongly Disagree' and 7 indicates 'Strongly Agree'. Higher scores indicate higher rates of craving. The CCQ was administered at three distinct time points: before the TSST, immediately after the TSST and 20 minutes post-TSST.&#xD;
The Trier Social Stress Test is a series of tasks which predictably induce stress in participants. First, physiological states are measured at baseline. Then participants are told they must prepare a 5 minute speech for a panel of researchers, which they then present. Participants are then asked verbal arithmetic questions. Finally, this is followed by a period of 5 minute rest referred to as the 'cooldown' period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Individual and Group Therapy Attendance Rates</measure>
    <time_frame>Visits 1-7, Up to 7 weeks</time_frame>
    <description>Aim 5: To evaluate the effectiveness of intranasal oxytocin on improving psychosocial treatment engagement (social support) as measured by individual and group therapy attendance rates.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cortisol Levels in Response to Trier Social Stress Test (TSST).</measure>
    <time_frame>Visits 1 and 7, up to 7 weeks</time_frame>
    <description>Aim 6: To evaluate the effectiveness of intranasal oxytocin on reducing stress biomarkers in response to the TSST.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dehydroepiandrosterone (DHEA) Levels in Response to Trier Social Stress Test (TSST)</measure>
    <time_frame>Visits 1 and 7, up to 7 weeks</time_frame>
    <description>Aim 6: To evaluate the effectiveness of intranasal oxytocin on reducing stress biomarkers in response to the TSST.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Self-reported Stress/Anxiety</measure>
    <time_frame>Visits 1 and 7, Up to 7 weeks</time_frame>
    <description>Aim 7: To evaluate the effectiveness of intranasal oxytocin on reducing self-reported stress/anxiety levels in response to the TSST. The scale used to measure anxiety was the State-Trait Anxiety Inventory (STAI-6). This scale consists of 40 questions, all of which are rated on a 4-point likert scale. 1 indicates 'Almost Never' while 4 indicates 'Almost Always'. The minimum score is 0, indicating no anxiety, and maximum score is 63, indicating severe anxiety.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">42</enrollment>
  <condition>Stimulant Use &amp; Co-occuring Opioid Use Disorders</condition>
  <arm_group>
    <arm_group_label>Oxytocin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients in methadone maintenance treatment (MMT) programs are required to come in every day for their methadone. Additionally they are required to come in weekly for psycho- educational/therapy groups, biweekly random urine screenings, and monthly individual therapy sessions. The investigators will piggy-back off this existing structure and randomize Veterans with stimulant use disorders and receiving MMT for co-occurring opioid use disorder (OUD) to receive either oxytocin or placebo, to be administered twice daily for six weeks while in the MMT program.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients in MMT programs are required to come in every day for their methadone. Additionally they are required to come in weekly for psycho- educational/therapy groups, biweekly random urine screenings, and monthly individual therapy sessions. The investigators will piggy-back off this existing structure and randomize Veterans with stimulant use disorders and receiving MMT for co-occurring OUD to receive either oxytocin or placebo, to be administered twice daily for six weeks while in the MMT program.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intranasal oxytocin</intervention_name>
    <description>Each Veteran with a stimulant use disorder, receiving MMT for OUD will receive a oxytocin nasal spray 40 International Units (IU) to be self administered twice daily over 6 weeks while in the MMT program. The veteran will come in for a total of 7 weekly visits. At baseline and during the last visit the veteran will complete at Trier Social Stress Test (TSST), and psychophysiological and biomarkers of stress will be collected. At every weekly visit a urine sample and self-reported drug use will be collected and therapy attendance will be recorded.</description>
    <arm_group_label>Oxytocin</arm_group_label>
    <other_name>Syntocinon</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intranasal placebo</intervention_name>
    <description>Each Veteran with a stimulant use disorder, receiving MMT for OUD will receive a placebo nasal spray 40IU to be self administered twice daily over 6 weeks while in the MMT program. The veteran will come in for a total of 7 weekly visits. At baseline and during the last visit the veteran will complete at Trier Social Stress Test (TSST), and psychophysiological and biomarkers of stress will be collected. At every weekly visit a urine sample and self-reported drug use will be collected and therapy attendance will be recorded.</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Saline placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. At least 18 years old&#xD;
&#xD;
          2. Enrolled as a patient who at the SFVAMC Opioid Treatment Program or the Oakland&#xD;
             Behavioral Health Clinic Opioid Treatment Program&#xD;
&#xD;
          3. Stable dose of opioid replacement therapy for at least 2 consecutive weeks&#xD;
&#xD;
          4. Veteran&#xD;
&#xD;
          5. One documented urine toxicology screen positive for stimulants in the past 12 months.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Severe neuropsychological disorder&#xD;
&#xD;
          2. Suicidal or homicidal ideation within the past 90 days or a suicide attempt in the&#xD;
             past 6 months&#xD;
&#xD;
          3. Hemodialysis, unless participant can produce urine samples weekly&#xD;
&#xD;
          4. Sensitivity to methylparaben or propylparaben&#xD;
&#xD;
          5. Positive urine pregnancy test or women of childbearing age not practicing effective&#xD;
             means of non-hormonal birth control&#xD;
&#xD;
          6. Chronic nasal obstruction, discharge, or bleeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christopher Stauffer, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>San Francisco VA Medical Center, San Francisco, CA</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>VA Northern California Health Care System, Mather, CA</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95655</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>San Francisco VA Medical Center, San Francisco, CA</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94121</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Portland Health Care System, Portland, OR</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.chrisstauffermd.com/</url>
    <description>Social Neuroscience &amp; Psychotherapy Lab</description>
  </link>
  <reference>
    <citation>Stauffer CS, Woolley JD. Can we bottle psychosocial treatments for addiction? The role of oxytocin. J Clin Psychiatry. 2014 Sep;75(9):1028-9. doi: 10.4088/JCP.14ac09437. No abstract available.</citation>
    <PMID>25295428</PMID>
  </reference>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>January 4, 2017</study_first_submitted>
  <study_first_submitted_qc>January 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 10, 2017</study_first_posted>
  <results_first_submitted>February 18, 2021</results_first_submitted>
  <results_first_submitted_qc>June 8, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">June 10, 2021</results_first_posted>
  <last_update_submitted>June 8, 2021</last_update_submitted>
  <last_update_submitted_qc>June 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 10, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>oxytocin</keyword>
  <keyword>substance-related disorders</keyword>
  <keyword>Opioid Replacement Therapy</keyword>
  <keyword>Psychophysiology</keyword>
  <keyword>Stress Biomarkers</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Opioid-Related Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Oxytocin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 18, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/98/NCT03016598/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 2, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/98/NCT03016598/SAP_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>August 8, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/98/NCT03016598/ICF_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>84 individuals assessed for eligibility, of which 38 were excluded. 28 of the 38 excluded were ineligible - 6 were lost to follow up and 4 were uninterested. The remaining 46 participants completed baseline assessment, of which 4 were excluded - 2 being ineligible, 1 being lost to follow up and the final being uninterested. Left remaining were 42 enrolled participants.</recruitment_details>
      <pre_assignment_details>42 individuals were enrolled, 2 of which were excluded due to being lost to follow up before being assigned to an arm.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Oxytocin</title>
          <description>Patients in MMT programs are required to come in every day for their methadone. Additionally they are required to come in weekly for psycho- educational/therapy groups, biweekly random urine screenings, and monthly individual therapy sessions. The investigators will piggy-back off this existing structure and randomize Veterans with stimulant use disorders and receiving MMT for co-occurring OUD to receive either oxytocin or placebo, to be administered twice daily for six weeks while in the MMT program.&#xD;
Intranasal oxytocin: Each Veteran with a stimulant use disorder, receiving MMT for OUD will receive a oxytocin nasal spray 40IU to be self administered twice daily over 6 weeks while in the MMT program. The veteran will come in for a total of 7 weekly visits. At baseline and during the last visit the veteran will complete at Trier Social Stress Test (TSST), and psychophysiological and biomarkers of stress will be collected. At every weekly visit a urine sample and self-reported drug use will be collected and therapy attendance will be recorded.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Patients in MMT programs are required to come in every day for their methadone. Additionally they are required to come in weekly for psycho- educational/therapy groups, biweekly random urine screenings, and monthly individual therapy sessions. The investigators will piggy-back off this existing structure and randomize Veterans with stimulant use disorders and receiving MMT for co-occurring OUD to receive either oxytocin or placebo, to be administered twice daily for six weeks while in the MMT program.&#xD;
Intranasal placebo: Each Veteran with a stimulant use disorder, receiving MMT for OUD will receive a placebo nasal spray 40IU to be self administered twice daily over 6 weeks while in the MMT program. The veteran will come in for a total of 7 weekly visits. At baseline and during the last visit the veteran will complete at Trier Social Stress Test (TSST), and psychophysiological and biomarkers of stress will be collected. At every weekly visit a urine sample and self-reported drug use will be collected and therapy attendance will be recorded.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Oxytocin</title>
          <description>Oxytocin, to be administered intranasally twice daily for six weeks. TSST will be conducted prior to study drug administration and after the 6-week course.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo, to be administered intranasally twice daily for six weeks. TSST will be conducted prior to study drug administration and after the 6-week course.</description>
        </group>
        <group group_id="B3">
          <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="18"/>
            <count group_id="B2" value="22"/>
            <count group_id="B3" value="40"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="53.94444" spread="11.35767"/>
                    <measurement group_id="B2" value="63.13636" spread="7.265676"/>
                    <measurement group_id="B3" value="59" spread="10.30061"/>
                  </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_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Stimulant Positive Drug Screen</title>
        <description>Aim 1: To evaluate the effectiveness of intranasal oxytocin on reducing stimulant use.</description>
        <time_frame>Baseline, Visits 1-7, up to 7 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oxytocin</title>
            <description>Oxytocin, to be administered intranasally twice daily for six weeks. TSST will be conducted prior to study drug administration and after the 6-week course.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo, to be administered intranasally twice daily for six weeks. TSST will be conducted prior to study drug administration and after the 6-week course.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Stimulant Positive Drug Screen</title>
          <description>Aim 1: To evaluate the effectiveness of intranasal oxytocin on reducing stimulant use.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Stimulant Positive: Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stimulant Positive: Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stimulant Postive: Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stimulant Positive: Week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stimulant Positive: Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stimulant Positive: Week 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stimulant Positive: Week 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stimulant Positive: Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Working Alliance Inventory (WAI)</title>
        <description>Aim 2: To evaluate the effectiveness of intranasal oxytocin on improving psychosocial treatment engagement (social support) as measured by the Working Alliance Inventory, an inventory of therapeutic alliance. The Working Alliance Inventory is a 36 question inventory. Each item is scored from 1-7, minimum = 1 and maximum = 7. Minimum total score = 36 to maximum total score = 252. Higher scores represent higher satisfaction.</description>
        <time_frame>Visits 1 and 7, Up to 7 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oxytocin</title>
            <description>Oxytocin, to be administered intranasally twice daily for six weeks. TSST will be conducted prior to study drug administration and after the 6-week course.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo, to be administered intranasally twice daily for six weeks. TSST will be conducted prior to study drug administration and after the 6-week course.</description>
          </group>
        </group_list>
        <measure>
          <title>Working Alliance Inventory (WAI)</title>
          <description>Aim 2: To evaluate the effectiveness of intranasal oxytocin on improving psychosocial treatment engagement (social support) as measured by the Working Alliance Inventory, an inventory of therapeutic alliance. The Working Alliance Inventory is a 36 question inventory. Each item is scored from 1-7, minimum = 1 and maximum = 7. Minimum total score = 36 to maximum total score = 252. Higher scores represent higher satisfaction.</description>
          <units>score 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="18"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>WAI Week 1: Self-Report</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.5972" spread="0.8816"/>
                    <measurement group_id="O2" value="3.8182" spread="0.8107"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>WAI Week 7: Self-Report</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.4676" spread="0.785"/>
                    <measurement group_id="O2" value="3.5208" spread="1.0516"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>WAI Week 1:Therapist</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.088" spread="0.7048"/>
                    <measurement group_id="O2" value="3.754" spread="0.7370"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>WAI Week 7: Therapist</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.1450" spread="0.7334"/>
                    <measurement group_id="O2" value="3.7486" spread="0.8308"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Heart Rate in Response to Trier Social Stress Test (TSST).</title>
        <description>Aim 3: To evaluate the effectiveness of intranasal oxytocin on reducing stress-related psycho-physiological measures in response to the Trier Social Stress Test (TSST).&#xD;
The Trier Social Stress Test is a series of tasks which predictably induce stress in participants. First, physiological states are measured at baseline. Then participants are told they must prepare a 5 minute speech for a panel of researchers, which they then present. Participants are then asked verbal arithmetic questions. Finally, this is followed by a period of 5 minute rest referred to as the 'cooldown' period.&#xD;
Heart rate was assessed at different time points during the TSST. These time point are as follows: baseline, during speech preparation, during speech presentation, during arithmetic problems, and during the cooldown period. Higher scores indicate higher stress levels.</description>
        <time_frame>Visits 1 and 7, up to 7 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oxytocin</title>
            <description>Oxytocin, to be administered intranasally twice daily for six weeks. TSST will be conducted prior to study drug administration and after the 6-week course.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo, to be administered intranasally twice daily for six weeks. TSST will be conducted prior to study drug administration and after the 6-week course.</description>
          </group>
        </group_list>
        <measure>
          <title>Heart Rate in Response to Trier Social Stress Test (TSST).</title>
          <description>Aim 3: To evaluate the effectiveness of intranasal oxytocin on reducing stress-related psycho-physiological measures in response to the Trier Social Stress Test (TSST).&#xD;
The Trier Social Stress Test is a series of tasks which predictably induce stress in participants. First, physiological states are measured at baseline. Then participants are told they must prepare a 5 minute speech for a panel of researchers, which they then present. Participants are then asked verbal arithmetic questions. Finally, this is followed by a period of 5 minute rest referred to as the 'cooldown' period.&#xD;
Heart rate was assessed at different time points during the TSST. These time point are as follows: baseline, during speech preparation, during speech presentation, during arithmetic problems, and during the cooldown period. Higher scores indicate higher stress levels.</description>
          <units>Beats/minute</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Heart Rate Baseline: Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="77.252" spread="8.34820"/>
                    <measurement group_id="O2" value="68.1912" spread="13.9445"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Heart Rate During Speech Prep: Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="77.5306" spread="11.1108"/>
                    <measurement group_id="O2" value="69.8634" spread="13.2503"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Heart Rate During Speech: Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="85.3146" spread="12.1203"/>
                    <measurement group_id="O2" value="79.4769" spread="15.1165"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Heart Rate During Arithmetic: Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="85.1227" spread="10.65619"/>
                    <measurement group_id="O2" value="77.8194" spread="15.6546"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Heart Rate Cooldown: Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="72.0023" spread="18.7152"/>
                    <measurement group_id="O2" value="68.8551" spread="12.1091"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Heart Rate Baseline: Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="76.116" spread="8.7493"/>
                    <measurement group_id="O2" value="72.6821" spread="11.9550"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Heart Rate During Speech Prep: Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="74.9320" spread="8.4512"/>
                    <measurement group_id="O2" value="69.9714" spread="12.1507"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Heart Rate During Speech: Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="81.8189" spread="8.1597"/>
                    <measurement group_id="O2" value="79.2512" spread="14.2214"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Heart Rate During Arithmetic: Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="82.6265" spread="8.4639"/>
                    <measurement group_id="O2" value="82.8517" spread="18.0291"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Heart Rate Cooldown: Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="74.9591" spread="9.8852"/>
                    <measurement group_id="O2" value="68.8543" spread="11.8623"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Respiratory Rate in Response to Trier Social Stress Test (TSST).</title>
        <description>Aim 3: To evaluate the effectiveness of intranasal oxytocin on reducing stress-related psycho-physiological measures in response to the Trier Social Stress Test (TSST).&#xD;
The Trier Social Stress Test is a series of tasks which predictably induce stress in participants. First, physiological states are measured at baseline. Then participants are told they must prepare a 5 minute speech for a panel of researchers, which they then present. Participants are then asked verbal arithmetic questions. Finally, this is followed by a period of 5 minute rest referred to as the 'cooldown' period.&#xD;
Respiratory rate was assessed at different time points during the TSST. These time point are as follows: baseline, during speech preparation, during speech presentation, during arithmetic problems, and during the cooldown period. Higher scores indicate higher stress levels.</description>
        <time_frame>Visits 1 and 7, up to 7 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oxytocin</title>
            <description>Oxytocin, to be administered intranasally twice daily for six weeks. TSST will be conducted prior to study drug administration and after the 6-week course.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo, to be administered intranasally twice daily for six weeks. TSST will be conducted prior to study drug administration and after the 6-week course.</description>
          </group>
        </group_list>
        <measure>
          <title>Respiratory Rate in Response to Trier Social Stress Test (TSST).</title>
          <description>Aim 3: To evaluate the effectiveness of intranasal oxytocin on reducing stress-related psycho-physiological measures in response to the Trier Social Stress Test (TSST).&#xD;
The Trier Social Stress Test is a series of tasks which predictably induce stress in participants. First, physiological states are measured at baseline. Then participants are told they must prepare a 5 minute speech for a panel of researchers, which they then present. Participants are then asked verbal arithmetic questions. Finally, this is followed by a period of 5 minute rest referred to as the 'cooldown' period.&#xD;
Respiratory rate was assessed at different time points during the TSST. These time point are as follows: baseline, during speech preparation, during speech presentation, during arithmetic problems, and during the cooldown period. Higher scores indicate higher stress levels.</description>
          <units>Breaths/minute</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Respiratory Rate Baseline: Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.9117" spread="1.5119"/>
                    <measurement group_id="O2" value="11.2000" spread="2.9642"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory Rate During Speech Prep: Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.0512" spread="3.3724"/>
                    <measurement group_id="O2" value="12.292" spread="2.9966"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory Rate During Speech: Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.4533" spread="2.976"/>
                    <measurement group_id="O2" value="12.3352" spread="2.9521"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory Rate During Arithmetic: Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.56" spread="1.7841"/>
                    <measurement group_id="O2" value="11.7565" spread="3.5337"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory Rate Cooldown: Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.6278" spread="3.0036"/>
                    <measurement group_id="O2" value="10.5266" spread="2.1028"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory Rate Baseline: Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.6779" spread="3.795"/>
                    <measurement group_id="O2" value="11.4583" spread="2.3595"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory Rate During Speech Prep: Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.6251" spread="1.8414"/>
                    <measurement group_id="O2" value="12.7914" spread="3.7546"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory Rate During Speech: Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.6675" spread="3.0857"/>
                    <measurement group_id="O2" value="11.5526" spread="3.304"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory Rate During Arithmetic: Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.4215" spread="1.9839"/>
                    <measurement group_id="O2" value="12.4459" spread="2.4201"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory Rate Cooldown: Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.9913" spread="2.6662"/>
                    <measurement group_id="O2" value="10.3816" spread="2.9001"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Respiratory Sinus Arrythmia (RSA) in Response to Trier Social Stress Test (TSST).</title>
        <description>Aim 3: To evaluate the effectiveness of intranasal oxytocin on reducing stress-related psycho-physiological measures in response to the Trier Social Stress Test (TSST).&#xD;
The Trier Social Stress Test is a series of tasks which predictably induce stress in participants. First, physiological states are measured at baseline. Then participants are told they must prepare a 5 minute speech for a panel of researchers, which they then present. Participants are then asked verbal arithmetic questions. Finally, this is followed by a period of 5 minute rest referred to as the 'cooldown' period.&#xD;
Respiratory sinus arrythmia (RSA) was assessed at different time points during the TSST. These time point are as follows: baseline, during speech preparation, during speech presentation, during arithmetic problems, and during the cooldown period. Higher scores indicate higher stress levels.</description>
        <time_frame>Visits 1 and 7, up to 7 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oxytocin</title>
            <description>Oxytocin, to be administered intranasally twice daily for six weeks. TSST will be conducted prior to study drug administration and after the 6-week course.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo, to be administered intranasally twice daily for six weeks. TSST will be conducted prior to study drug administration and after the 6-week course.</description>
          </group>
        </group_list>
        <measure>
          <title>Respiratory Sinus Arrythmia (RSA) in Response to Trier Social Stress Test (TSST).</title>
          <description>Aim 3: To evaluate the effectiveness of intranasal oxytocin on reducing stress-related psycho-physiological measures in response to the Trier Social Stress Test (TSST).&#xD;
The Trier Social Stress Test is a series of tasks which predictably induce stress in participants. First, physiological states are measured at baseline. Then participants are told they must prepare a 5 minute speech for a panel of researchers, which they then present. Participants are then asked verbal arithmetic questions. Finally, this is followed by a period of 5 minute rest referred to as the 'cooldown' period.&#xD;
Respiratory sinus arrythmia (RSA) was assessed at different time points during the TSST. These time point are as follows: baseline, during speech preparation, during speech presentation, during arithmetic problems, and during the cooldown period. Higher scores indicate higher stress levels.</description>
          <units>milliseconds squared</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Respiratory Sinus Arrythmia During Baseline: Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.2435" spread="1.2701"/>
                    <measurement group_id="O2" value="4.9543" spread="1.8461"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory Sinus Arrythmia During Speech Prep: Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.6264" spread="1.2903"/>
                    <measurement group_id="O2" value="4.7393" spread="1.5292"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory Sinus Arrythmia During Speech: Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.5542" spread="1.2285"/>
                    <measurement group_id="O2" value="3.8212" spread="1.3293"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory Sinus Arrythmia During Arithmetic: Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.5364" spread="1.1521"/>
                    <measurement group_id="O2" value="3.7893" spread="1.1818"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory Sinus Arrythmia During Cooldown: Week1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.3466" spread="1.0783"/>
                    <measurement group_id="O2" value="4.4933" spread="1.3137"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory Sinus Arrythmia During Baseline: Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.1866" spread="1.1912"/>
                    <measurement group_id="O2" value="4.053" spread="1.7715"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory Sinus Arrythmia During Speech Prep: Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.0099" spread="1.3911"/>
                    <measurement group_id="O2" value="4.2972" spread="1.6850"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory Sinus Arrythmia During Speech: Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.6254" spread="1.3660"/>
                    <measurement group_id="O2" value="3.5998" spread="1.523"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory Sinus Arrythmia During Arithmetic: Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.4825" spread="1.3147"/>
                    <measurement group_id="O2" value="3.5267" spread="1.3283"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory Sinus Arrythmia During Cooldown: Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.9752" spread="1.4793"/>
                    <measurement group_id="O2" value="4.1651" spread="1.5196"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Root Mean Square of Successive Differences (RMSSD) of Heart Rate Variability in Response to Trier Social Stress Test (TSST).</title>
        <description>Aim 3: To evaluate the effectiveness of intranasal oxytocin on reducing stress-related psycho-physiological measures in response to the Trier Social Stress Test (TSST).&#xD;
The Trier Social Stress Test is a series of tasks which predictably induce stress in participants. First, physiological states are measured at baseline. Then participants are told they must prepare a 5 minute speech for a panel of researchers, which they then present. Participants are then asked verbal arithmetic questions. Finally, this is followed by a period of 5 minute rest referred to as the 'cooldown' period.&#xD;
The root mean square of successive differences (RMSSD) were assessed at different time points during the TSST. These time point are as follows: baseline, during speech preparation, during speech presentation, during arithmetic problems, and during the cooldown period. Higher scores indicate higher stress levels. Calculated by measuring each successive time difference between heartbeats in ms.</description>
        <time_frame>Visits 1 and 7, up to 7 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oxytocin</title>
            <description>Oxytocin, to be administered intranasally twice daily for six weeks. TSST will be conducted prior to study drug administration and after the 6-week course.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo, to be administered intranasally twice daily for six weeks. TSST will be conducted prior to study drug administration and after the 6-week course.</description>
          </group>
        </group_list>
        <measure>
          <title>Root Mean Square of Successive Differences (RMSSD) of Heart Rate Variability in Response to Trier Social Stress Test (TSST).</title>
          <description>Aim 3: To evaluate the effectiveness of intranasal oxytocin on reducing stress-related psycho-physiological measures in response to the Trier Social Stress Test (TSST).&#xD;
The Trier Social Stress Test is a series of tasks which predictably induce stress in participants. First, physiological states are measured at baseline. Then participants are told they must prepare a 5 minute speech for a panel of researchers, which they then present. Participants are then asked verbal arithmetic questions. Finally, this is followed by a period of 5 minute rest referred to as the 'cooldown' period.&#xD;
The root mean square of successive differences (RMSSD) were assessed at different time points during the TSST. These time point are as follows: baseline, during speech preparation, during speech presentation, during arithmetic problems, and during the cooldown period. Higher scores indicate higher stress levels. Calculated by measuring each successive time difference between heartbeats in ms.</description>
          <units>milliseconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>RMSSD During Baseline: Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.8196" spread="41.5701"/>
                    <measurement group_id="O2" value="48.865" spread="48.2147"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>RMSSD During Speech Prep: Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.5447" spread="38.5287"/>
                    <measurement group_id="O2" value="37.7607" spread="44.6989"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>RMSSD During Speech: Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.5526" spread="44.3238"/>
                    <measurement group_id="O2" value="20.9388" spread="21.2336"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>RMSSD During Arithmetic: Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.113" spread="39.3470"/>
                    <measurement group_id="O2" value="21.1729" spread="18.4126"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>RMSSD During Cooldown: Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.7325" spread="53.4858"/>
                    <measurement group_id="O2" value="34.5220" spread="43.9497"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>RMSSD During Baseline Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.7941" spread="9.0513"/>
                    <measurement group_id="O2" value="26.3299" spread="30.7912"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>RMSSD During Speech Prep: Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.0198" spread="9.2258"/>
                    <measurement group_id="O2" value="28.1708" spread="31.7601"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>RMSSD During Speech: Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.9299" spread="7.5432"/>
                    <measurement group_id="O2" value="22.1121" spread="30.6961"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>RMSSD During Arithmetic: Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.3174" spread="6.5779"/>
                    <measurement group_id="O2" value="21.2057" spread="32.3207"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>RMSSD During Cooldown: Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.9728" spread="13.0228"/>
                    <measurement group_id="O2" value="24.6587" spread="20.8481"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Self-reported Stimulant Craving</title>
        <description>Aim 4: To evaluate the effectiveness of intranasal oxytocin on reducing stimulant craving in response the Trier Social Stress Test (TSST).&#xD;
The Cocaine Craving Questionnaire (CCQ) (brief) was modified to include all stimulants and administered. The CCQ is a 10-item questionnaire, with each item ranking on a scale of 1-7. 1 indicates 'Strongly Disagree' and 7 indicates 'Strongly Agree'. Higher scores indicate higher rates of craving. The CCQ was administered at three distinct time points: before the TSST, immediately after the TSST and 20 minutes post-TSST.&#xD;
The Trier Social Stress Test is a series of tasks which predictably induce stress in participants. First, physiological states are measured at baseline. Then participants are told they must prepare a 5 minute speech for a panel of researchers, which they then present. Participants are then asked verbal arithmetic questions. Finally, this is followed by a period of 5 minute rest referred to as the 'cooldown' period.</description>
        <time_frame>Visits 1 and 7, Up to 7 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oxytocin</title>
            <description>Oxytocin, to be administered intranasally twice daily for six weeks. TSST will be conducted prior to study drug administration and after the 6-week course.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo, to be administered intranasally twice daily for six weeks. TSST will be conducted prior to study drug administration and after the 6-week course.</description>
          </group>
        </group_list>
        <measure>
          <title>Self-reported Stimulant Craving</title>
          <description>Aim 4: To evaluate the effectiveness of intranasal oxytocin on reducing stimulant craving in response the Trier Social Stress Test (TSST).&#xD;
The Cocaine Craving Questionnaire (CCQ) (brief) was modified to include all stimulants and administered. The CCQ is a 10-item questionnaire, with each item ranking on a scale of 1-7. 1 indicates 'Strongly Disagree' and 7 indicates 'Strongly Agree'. Higher scores indicate higher rates of craving. The CCQ was administered at three distinct time points: before the TSST, immediately after the TSST and 20 minutes post-TSST.&#xD;
The Trier Social Stress Test is a series of tasks which predictably induce stress in participants. First, physiological states are measured at baseline. Then participants are told they must prepare a 5 minute speech for a panel of researchers, which they then present. Participants are then asked verbal arithmetic questions. Finally, this is followed by a period of 5 minute rest referred to as the 'cooldown' period.</description>
          <units>score 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="18"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pre_Trier: Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.1667" spread="1.1827"/>
                    <measurement group_id="O2" value="1.82727" spread="1.1707"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Imm_Post_Trier: Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.4389" spread="1.7446"/>
                    <measurement group_id="O2" value="2.35" spread="1.6964"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>20m_Post_Trier: Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.3056" spread="1.4941"/>
                    <measurement group_id="O2" value="1.8955" spread="1.2688"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre_Trier: Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.7167" spread="1.0755"/>
                    <measurement group_id="O2" value="1.42" spread="0.7135"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Imm_Post_Trier: Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.6833" spread="0.8535"/>
                    <measurement group_id="O2" value="1.48" spread="0.818"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>20m_Post_Trier: Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.7167" spread="1.058"/>
                    <measurement group_id="O2" value="1.67" spread="1.0255"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Individual and Group Therapy Attendance Rates</title>
        <description>Aim 5: To evaluate the effectiveness of intranasal oxytocin on improving psychosocial treatment engagement (social support) as measured by individual and group therapy attendance rates.</description>
        <time_frame>Visits 1-7, Up to 7 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oxytocin</title>
            <description>Oxytocin, to be administered intranasally twice daily for six weeks. TSST will be conducted prior to study drug administration and after the 6-week course.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo, to be administered intranasally twice daily for six weeks. TSST will be conducted prior to study drug administration and after the 6-week course.</description>
          </group>
        </group_list>
        <measure>
          <title>Individual and Group Therapy Attendance Rates</title>
          <description>Aim 5: To evaluate the effectiveness of intranasal oxytocin on improving psychosocial treatment engagement (social support) as measured by individual and group therapy attendance rates.</description>
          <units>proportion of OTP visits attended</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Attendance Proportion: Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.9352" spread="0.1416"/>
                    <measurement group_id="O2" value="0.8406" spread="0.3047"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Attendance Proportion: Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.9333" spread="0.1183"/>
                    <measurement group_id="O2" value="0.8485" spread="0.2951"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Attendance Proportion: Week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.9241" spread="0.1652"/>
                    <measurement group_id="O2" value="0.8429" spread="0.3022"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Attendance Proportion: Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.9260" spread="0.1828"/>
                    <measurement group_id="O2" value="0.7857" spread="0.3580"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Attendance Proportion: Week 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8704" spread="0.2181"/>
                    <measurement group_id="O2" value="0.7476" spread="0.3572"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Attendance Proportion: Week 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.9444" spread="0.1560"/>
                    <measurement group_id="O2" value="0.7483" spread="0.3915"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Attendance Proportion: Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1" spread="0"/>
                    <measurement group_id="O2" value="0.75" spread="0.4443"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cortisol Levels in Response to Trier Social Stress Test (TSST).</title>
        <description>Aim 6: To evaluate the effectiveness of intranasal oxytocin on reducing stress biomarkers in response to the TSST.</description>
        <time_frame>Visits 1 and 7, up to 7 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oxytocin</title>
            <description>Oxytocin, to be administered intranasally twice daily for six weeks. TSST will be conducted prior to study drug administration and after the 6-week course.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo, to be administered intranasally twice daily for six weeks. TSST will be conducted prior to study drug administration and after the 6-week course.</description>
          </group>
        </group_list>
        <measure>
          <title>Cortisol Levels in Response to Trier Social Stress Test (TSST).</title>
          <description>Aim 6: To evaluate the effectiveness of intranasal oxytocin on reducing stress biomarkers in response to the TSST.</description>
          <units>(ug/dL)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Initial Cortisol Levels (ug/dL) Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.331" spread="0.263"/>
                    <measurement group_id="O2" value="0.319" spread="0.335"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-Trier Cortisol Levels (ug/dL) Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.283" spread="0.213"/>
                    <measurement group_id="O2" value="0.193" spread="0.163"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Immediately Post-Trier Cortisol Levels (ug/dL) Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.286" spread="0.221"/>
                    <measurement group_id="O2" value="0.242" spread="0.286"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>20Minutes Post-Trier Cortisol Levels (ug/dL) Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.29" spread="0.184"/>
                    <measurement group_id="O2" value="0.211" spread="0.245"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Initial Cortisol Levels (ug/dL) Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.206" spread="0.155"/>
                    <measurement group_id="O2" value="0.259" spread="0.154"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-Trier Cortisol Levels (ug/dL) Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.156" spread="0.093"/>
                    <measurement group_id="O2" value="0.197" spread="0.115"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Immediately Post-Trier Cortisol Levels (ug/dL) Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.167" spread="0.112"/>
                    <measurement group_id="O2" value="0.184" spread="0.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>20 Minutes Post-Trier Cortisol Levels (ug/dL) Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.175" spread="0.130"/>
                    <measurement group_id="O2" value="0.168" spread="0.073"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Dehydroepiandrosterone (DHEA) Levels in Response to Trier Social Stress Test (TSST)</title>
        <description>Aim 6: To evaluate the effectiveness of intranasal oxytocin on reducing stress biomarkers in response to the TSST.</description>
        <time_frame>Visits 1 and 7, up to 7 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oxytocin</title>
            <description>Oxytocin, to be administered intranasally twice daily for six weeks. TSST will be conducted prior to study drug administration and after the 6-week course.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo, to be administered intranasally twice daily for six weeks. TSST will be conducted prior to study drug administration and after the 6-week course.</description>
          </group>
        </group_list>
        <measure>
          <title>Dehydroepiandrosterone (DHEA) Levels in Response to Trier Social Stress Test (TSST)</title>
          <description>Aim 6: To evaluate the effectiveness of intranasal oxytocin on reducing stress biomarkers in response to the TSST.</description>
          <units>(pg/mL)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Initial DHEA Levels (pg/mL) Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="86.230" spread="52.999"/>
                    <measurement group_id="O2" value="62.695" spread="67.462"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-Trier DHEA Levels (pg/mL) Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="90.313" spread="80.944"/>
                    <measurement group_id="O2" value="52.32" spread="55.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Immediately Post-Trier DHEA Levels (pg/mL) Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.468" spread="76.830"/>
                    <measurement group_id="O2" value="63.471" spread="57.251"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>20 Minutes Post-Trier DHEA Levels (pg/mL) Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="81.742" spread="68.051"/>
                    <measurement group_id="O2" value="54.816" spread="52.980"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Initial DHEA Levels(pg/mL) Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="87.674" spread="78.363"/>
                    <measurement group_id="O2" value="61.581" spread="77.382"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-Trier DHEA Levels (pg/mL) Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="75.221" spread="80.167"/>
                    <measurement group_id="O2" value="54.324" spread="57.183"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Immediately Post-Trier DHEA Levels (pg/mL) Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="84.230" spread="72.875"/>
                    <measurement group_id="O2" value="69.291" spread="108.134"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>20 Minutes Post-Trier DHEA Levels (pg/mL) Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="82.009" spread="86.669"/>
                    <measurement group_id="O2" value="66.736" spread="103.362"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Self-reported Stress/Anxiety</title>
        <description>Aim 7: To evaluate the effectiveness of intranasal oxytocin on reducing self-reported stress/anxiety levels in response to the TSST. The scale used to measure anxiety was the State-Trait Anxiety Inventory (STAI-6). This scale consists of 40 questions, all of which are rated on a 4-point likert scale. 1 indicates 'Almost Never' while 4 indicates 'Almost Always'. The minimum score is 0, indicating no anxiety, and maximum score is 63, indicating severe anxiety.</description>
        <time_frame>Visits 1 and 7, Up to 7 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oxytocin</title>
            <description>Oxytocin, to be administered intranasally twice daily for six weeks. TSST will be conducted prior to study drug administration and after the 6-week course.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo, to be administered intranasally twice daily for six weeks. TSST will be conducted prior to study drug administration and after the 6-week course.</description>
          </group>
        </group_list>
        <measure>
          <title>Self-reported Stress/Anxiety</title>
          <description>Aim 7: To evaluate the effectiveness of intranasal oxytocin on reducing self-reported stress/anxiety levels in response to the TSST. The scale used to measure anxiety was the State-Trait Anxiety Inventory (STAI-6). This scale consists of 40 questions, all of which are rated on a 4-point likert scale. 1 indicates 'Almost Never' while 4 indicates 'Almost Always'. The minimum score is 0, indicating no anxiety, and maximum score is 63, indicating severe anxiety.</description>
          <units>score 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="18"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pre_Trier: Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="34.815" spread="13.778"/>
                    <measurement group_id="O2" value="32.2727" spread="11.0978"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Imm_Post_Trier: Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.4815" spread="15.529"/>
                    <measurement group_id="O2" value="46.0606" spread="19.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>20m_Post_Trier: Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.8519" spread="14.4834"/>
                    <measurement group_id="O2" value="36.97" spread="14.5809"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre_Trier: Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.185" spread="12.379"/>
                    <measurement group_id="O2" value="29.17" spread="11.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Imm_Post_Trier: Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.222" spread="15.966"/>
                    <measurement group_id="O2" value="36.5" spread="11.7217"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>20m_Post_Trier: Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.741" spread="11.871"/>
                    <measurement group_id="O2" value="31" spread="11.726"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>18 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Oxytocin</title>
          <description>Oxytocin, to be administered intranasally twice daily for six weeks. TSST will be conducted prior to study drug administration and after the 6-week course.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo, to be administered intranasally twice daily for six weeks. TSST will be conducted prior to study drug administration and after the 6-week course.</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="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
              </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="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <description>Participant (Subject Identifier (ID)# 730) was admitted to the San Francisco Veteran Affairs (SFVA) ER for constipation on 3/30/2019 and 4/10/2019. He was discharged on the same day for both events.</description>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Hallucination</sub_title>
                <description>Participant (Subject ID# 731) reported dream-like hallucination that subsided after 2 seconds. Participant reported methamphetamine use prior to hallucination, and the event did not result in participant injury.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Stinging sensation</sub_title>
                <description>Participant (Subject ID# 730) reported a stinging sensation and was examined by study physician, who did not observe irritation. Participant said sensation subsided, and remarked. 'It must've been a zit'.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="22"/>
              </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>
    <point_of_contact>
      <name_or_title>Delaney.McKechnie@va.gov</name_or_title>
      <organization>Portland VA</organization>
      <phone>360-696-4061 ext 32017</phone>
      <email>Delaney.McKechnie@va.gov</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/NCT03016598
org study id: NURA-014-16S
secondary id: 1IK2CX001495-01
nct id: NCT03016598
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This study will investigate the effects of intranasal administration of oxytocin, a social
      neuropeptide, on reducing stimulant use, enhancing therapeutic engagement, and susceptibility
      to stress-induced relapse in Veterans with stimulant use disorders and enrolled in opioid
      replacement therapy (ORT) program for co-occurring opioid use disorder (OUD).
High rates of substance use disorders (SUDs) in Veterans compared to the general population
      are heavily influenced by psychosocial factors - such as difficulty reintegrating into
      civilian life due to avoidance of vital support systems - leading to disproportionately
      elevated unmet addiction treatment needs. Although the gold standard for treatment for most
      SUDs involves pharmacological interventions, there are currently no effective pharmacological
      interventions approved by the Federal Drug Administration for stimulant users, who have the
      most difficulty adhering to treatment programs and the most susceptibility to stress-induced
      relapse of any SUD. Administering oxytocin, a mammalian neuropeptide, intranasally to healthy
      controls facilitates the stress-buffering properties of social support. Oxytocin may also
      have an independent role in mitigating the symptoms of SUDs. For example, in animal models of
      addiction, oxytocin administration directly reduces tolerance, withdrawal effects,
      self-administration, and stress-induced reinstatement of drug seeking for a range of
      addictive substances. A more integrated understanding of oxytocin's distinct effects on the
      behavior and psychology of 1) addiction, 2) sociality, and 3) stress reactivity could be the
      key to defining oxytocin's role in SUD treatment. This study proposes to translate promising
      preclinical and early proof-of-concept clinical results related to the anti-addiction,
      pro-social, and stress-tempering properties of oxytocin administration in Veterans with
      moderate-severe stimulant use disorders enrolled in a opioid replacement therapy (ORT)
      program for co-occurring opioid use disorder (OUD) at the San Francisco VA Medical Center
      (SFVAMC). The investigators' primary outcome is Aim 1) reduction in stimulant use, as
      measured by stimulant positive urine drug screen. Secondarily, the investigators will focus
      on Aim 2) improving psychosocial treatment engagement (social support) and Aim 3) mitigating
      social stress-related relapse, targeting two important barriers to stimulant use disorder
      recovery likely to respond to oxytocin administration.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of Participants With Stimulant Positive Drug Screen
time frame: Baseline, Visits 1-7, up to 7 weeks
description: Aim 1: To evaluate the effectiveness of intranasal oxytocin on reducing stimulant use.
measure: Working Alliance Inventory (WAI)
time frame: Visits 1 and 7, Up to 7 weeks
description: Aim 2: To evaluate the effectiveness of intranasal oxytocin on improving psychosocial treatment engagement (social support) as measured by the Working Alliance Inventory, an inventory of therapeutic alliance. The Working Alliance Inventory is a 36 question inventory. Each item is scored from 1-7, minimum = 1 and maximum = 7. Minimum total score = 36 to maximum total score = 252. Higher scores represent higher satisfaction.
measure: Heart Rate in Response to Trier Social Stress Test (TSST).
time frame: Visits 1 and 7, up to 7 weeks
description: Aim 3: To evaluate the effectiveness of intranasal oxytocin on reducing stress-related psycho-physiological measures in response to the Trier Social Stress Test (TSST).
The Trier Social Stress Test is a series of tasks which predictably induce stress in participants. First, physiological states are measured at baseline. Then participants are told they must prepare a 5 minute speech for a panel of researchers, which they then present. Participants are then asked verbal arithmetic questions. Finally, this is followed by a period of 5 minute rest referred to as the 'cooldown' period.
Heart rate was assessed at different time points during the TSST. These time point are as follows: baseline, during speech preparation, during speech presentation, during arithmetic problems, and during the cooldown period. Higher scores indicate higher stress levels.
measure: Respiratory Rate in Response to Trier Social Stress Test (TSST).
time frame: Visits 1 and 7, up to 7 weeks
description: Aim 3: To evaluate the effectiveness of intranasal oxytocin on reducing stress-related psycho-physiological measures in response to the Trier Social Stress Test (TSST).
The Trier Social Stress Test is a series of tasks which predictably induce stress in participants. First, physiological states are measured at baseline. Then participants are told they must prepare a 5 minute speech for a panel of researchers, which they then present. Participants are then asked verbal arithmetic questions. Finally, this is followed by a period of 5 minute rest referred to as the 'cooldown' period.
Respiratory rate was assessed at different time points during the TSST. These time point are as follows: baseline, during speech preparation, during speech presentation, during arithmetic problems, and during the cooldown period. Higher scores indicate higher stress levels.
measure: Respiratory Sinus Arrythmia (RSA) in Response to Trier Social Stress Test (TSST).
time frame: Visits 1 and 7, up to 7 weeks
description: Aim 3: To evaluate the effectiveness of intranasal oxytocin on reducing stress-related psycho-physiological measures in response to the Trier Social Stress Test (TSST).
The Trier Social Stress Test is a series of tasks which predictably induce stress in participants. First, physiological states are measured at baseline. Then participants are told they must prepare a 5 minute speech for a panel of researchers, which they then present. Participants are then asked verbal arithmetic questions. Finally, this is followed by a period of 5 minute rest referred to as the 'cooldown' period.
Respiratory sinus arrythmia (RSA) was assessed at different time points during the TSST. These time point are as follows: baseline, during speech preparation, during speech presentation, during arithmetic problems, and during the cooldown period. Higher scores indicate higher stress levels.
measure: Root Mean Square of Successive Differences (RMSSD) of Heart Rate Variability in Response to Trier Social Stress Test (TSST).
time frame: Visits 1 and 7, up to 7 weeks
description: Aim 3: To evaluate the effectiveness of intranasal oxytocin on reducing stress-related psycho-physiological measures in response to the Trier Social Stress Test (TSST).
The Trier Social Stress Test is a series of tasks which predictably induce stress in participants. First, physiological states are measured at baseline. Then participants are told they must prepare a 5 minute speech for a panel of researchers, which they then present. Participants are then asked verbal arithmetic questions. Finally, this is followed by a period of 5 minute rest referred to as the 'cooldown' period.
The root mean square of successive differences (RMSSD) were assessed at different time points during the TSST. These time point are as follows: baseline, during speech preparation, during speech presentation, during arithmetic problems, and during the cooldown period. Higher scores indicate higher stress levels. Calculated by measuring each successive time difference between heartbeats in ms.
measure: Self-reported Stimulant Craving
time frame: Visits 1 and 7, Up to 7 weeks
description: Aim 4: To evaluate the effectiveness of intranasal oxytocin on reducing stimulant craving in response the Trier Social Stress Test (TSST).
The Cocaine Craving Questionnaire (CCQ) (brief) was modified to include all stimulants and administered. The CCQ is a 10-item questionnaire, with each item ranking on a scale of 1-7. 1 indicates 'Strongly Disagree' and 7 indicates 'Strongly Agree'. Higher scores indicate higher rates of craving. The CCQ was administered at three distinct time points: before the TSST, immediately after the TSST and 20 minutes post-TSST.
The Trier Social Stress Test is a series of tasks which predictably induce stress in participants. First, physiological states are measured at baseline. Then participants are told they must prepare a 5 minute speech for a panel of researchers, which they then present. Participants are then asked verbal arithmetic questions. Finally, this is followed by a period of 5 minute rest referred to as the 'cooldown' period.
measure: Individual and Group Therapy Attendance Rates
time frame: Visits 1-7, Up to 7 weeks
description: Aim 5: To evaluate the effectiveness of intranasal oxytocin on improving psychosocial treatment engagement (social support) as measured by individual and group therapy attendance rates.
measure: Cortisol Levels in Response to Trier Social Stress Test (TSST).
time frame: Visits 1 and 7, up to 7 weeks
description: Aim 6: To evaluate the effectiveness of intranasal oxytocin on reducing stress biomarkers in response to the TSST.
measure: Dehydroepiandrosterone (DHEA) Levels in Response to Trier Social Stress Test (TSST)
time frame: Visits 1 and 7, up to 7 weeks
description: Aim 6: To evaluate the effectiveness of intranasal oxytocin on reducing stress biomarkers in response to the TSST.
measure: Self-reported Stress/Anxiety
time frame: Visits 1 and 7, Up to 7 weeks
description: Aim 7: To evaluate the effectiveness of intranasal oxytocin on reducing self-reported stress/anxiety levels in response to the TSST. The scale used to measure anxiety was the State-Trait Anxiety Inventory (STAI-6). This scale consists of 40 questions, all of which are rated on a 4-point likert scale. 1 indicates 'Almost Never' while 4 indicates 'Almost Always'. The minimum score is 0, indicating no anxiety, and maximum score is 63, indicating severe anxiety.
arm group label: Oxytocin
arm group type: Experimental
description: Patients in methadone maintenance treatment (MMT) programs are required to come in every day for their methadone. Additionally they are required to come in weekly for psycho- educational/therapy groups, biweekly random urine screenings, and monthly individual therapy sessions. The investigators will piggy-back off this existing structure and randomize Veterans with stimulant use disorders and receiving MMT for co-occurring opioid use disorder (OUD) to receive either oxytocin or placebo, to be administered twice daily for six weeks while in the MMT program.
arm group label: Placebo
arm group type: Placebo Comparator
description: Patients in MMT programs are required to come in every day for their methadone. Additionally they are required to come in weekly for psycho- educational/therapy groups, biweekly random urine screenings, and monthly individual therapy sessions. The investigators will piggy-back off this existing structure and randomize Veterans with stimulant use disorders and receiving MMT for co-occurring OUD to receive either oxytocin or placebo, to be administered twice daily for six weeks while in the MMT program.
intervention type: Drug
intervention name: Intranasal oxytocin
description: Each Veteran with a stimulant use disorder, receiving MMT for OUD will receive a oxytocin nasal spray 40 International Units (IU) to be self administered twice daily over 6 weeks while in the MMT program. The veteran will come in for a total of 7 weekly visits. At baseline and during the last visit the veteran will complete at Trier Social Stress Test (TSST), and psychophysiological and biomarkers of stress will be collected. At every weekly visit a urine sample and self-reported drug use will be collected and therapy attendance will be recorded.
arm group label: Oxytocin
other name: Syntocinon
intervention type: Drug
intervention name: Intranasal placebo
description: Each Veteran with a stimulant use disorder, receiving MMT for OUD will receive a placebo nasal spray 40IU to be self administered twice daily over 6 weeks while in the MMT program. The veteran will come in for a total of 7 weekly visits. At baseline and during the last visit the veteran will complete at Trier Social Stress Test (TSST), and psychophysiological and biomarkers of stress will be collected. At every weekly visit a urine sample and self-reported drug use will be collected and therapy attendance will be recorded.
arm group label: Placebo
other name: Saline placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Christopher Stauffer, MD
role: Principal Investigator
affiliation: San Francisco VA Medical Center, San Francisco, CA
facility: 
facility: 
facility: 
country: United States
url: https://www.chrisstauffermd.com/
description: Social Neuroscience & Psychotherapy Lab
citation: Stauffer CS, Woolley JD. Can we bottle psychosocial treatments for addiction? The role of oxytocin. J Clin Psychiatry. 2014 Sep;75(9):1028-9. doi: 10.4088/JCP.14ac09437. No abstract available.
PMID: 25295428
responsible party type: Sponsor
mesh term: Opioid-Related Disorders
mesh term: Oxytocin
sharing ipd: No
provided document: 
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 