<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/NCT02251912</url>
  </required_header>
  <id_info>
    <org_study_id>12-1862b</org_study_id>
    <secondary_id>1R21AA021927-01A1</secondary_id>
    <nct_id>NCT02251912</nct_id>
  </id_info>
  <brief_title>Oxytocin Treatment of Alcohol Dependence</brief_title>
  <acronym>OTETOH-3</acronym>
  <official_title>Oxytocin Treatment of Alcohol Dependence: A Randomized, Placebo-Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of North Carolina, Chapel Hill</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Alcohol Abuse and Alcoholism (NIAAA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of North Carolina, Chapel Hill</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Purpose: Test whether oxytocin treatment decreases drinking in people who have been consuming&#xD;
      alcohol heavily for long periods and are physically and psychologically dependent on alcohol.&#xD;
&#xD;
      Participants: 50 adults with alcohol dependence&#xD;
&#xD;
      Procedures (methods): Oxytocin or placebo will be administered three times a day for the&#xD;
      first 2 days followed by twice daily intranasal doses for the rest of the 12 weeks. Before,&#xD;
      during and at the end of the trial, each subject will undergo evaluations including&#xD;
      breathalyzer readings, rating withdrawal symptoms, interviews about amount of alcohol&#xD;
      consumed since last clinic visit, subject self-ratings of anxiety, alcohol craving and, at&#xD;
      some visits, laboratory measures (blood and urine) to monitor safety and alcohol/drug use.&#xD;
      Following the active phase of the trial, subjects will be followed up at 4 weeks and 12 weeks&#xD;
      to evaluate for post-medication safety and efficacy&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this research study is to learn whether oxytocin treatment decreases drinking&#xD;
      and alcohol craving in people who have been consuming alcohol heavily for long periods and&#xD;
      are unable to stop drinking on their own. Oxytocin is made naturally and is released in parts&#xD;
      of the brain where it acts like a chemical signal from one cell to another. Oxytocin is&#xD;
      approved by the Food and Drug Administration for stimulating labor in pregnant women but is&#xD;
      not approved as a treatment to decrease alcohol drinking.&#xD;
&#xD;
      People who drink large amounts of alcohol every day or many days per week for weeks or months&#xD;
      undergo chemical changes in their brains. They continue to drink frequently and heavily&#xD;
      because, even though they may know drinking is not good for their health, they experience&#xD;
      unpleasant symptoms if they stop or decrease drinking. Those symptoms can include increased&#xD;
      anxiety, difficulty sleeping, difficulty tolerating stress, mild to moderate withdrawal&#xD;
      symptoms such as tremors, nausea, feeling sweaty and/or headaches, and cravings to drink.&#xD;
      Studies found that giving oxytocin to alcohol-addicted animals reduced symptoms when they&#xD;
      were put into alcohol withdrawal. A pilot study conducted at UNC found that twice daily&#xD;
      intranasal doses of oxytocin decreased withdrawal symptoms in heavy drinkers who were&#xD;
      admitted to a hospital for medical detoxification to come off alcohol.&#xD;
&#xD;
      This study will test whether daily intranasal oxytocin treatment for 12 weeks will decrease&#xD;
      how much subjects drink as well as craving for alcohol and anxiety.&#xD;
&#xD;
      Prospective subjects must have been drinking large amounts of alcohol for a sustained period&#xD;
      to qualify for this study and want help to stop or cut back on their drinking. Subjects will&#xD;
      self-administer oxytocin or placebo in this study in an intranasal spray. The placebo spray&#xD;
      contains all of the ingredients of the oxytocin spray EXCEPT oxytocin. Subjects' assignment&#xD;
      to oxytocin or placebo treatment will be random (like a flip of a coin).&#xD;
&#xD;
      Subjects must sign a consent form to take part in this study. Their participation in the&#xD;
      study will last up to 14-15 weeks. Prospective subjects will be recruited from the community&#xD;
      through advertisements (radio, social media, mass emails, etc). Those who respond to&#xD;
      advertisements will undergo initial screening over the phone. Prospective subjects who appear&#xD;
      to meet study criteria based on the phone screen will give informed consent and undergo more&#xD;
      detailed evaluation during a screening clinic visit. If they are found to meet study&#xD;
      criteria, they will shortly thereafter attend another clinic visit (randomization clinic&#xD;
      visit) during which they will be randomized to oxytocin or placebo treatment and take their&#xD;
      first test dose under study personnel supervision. They will then take home the bottle&#xD;
      contained the intranasal study medication to which they have been randomized and&#xD;
      self-administer intranasal test doses at home for the remainder of the 12-week test treatment&#xD;
      period. New intranasal spray bottles will be exchanged for old every 2 weeks. Subjects will&#xD;
      attend 8 additional clinic visits over a 12 week period after the randomization clinic visit.&#xD;
      Each clinic visit will last 1-2 hours.&#xD;
&#xD;
      Procedures during screening clinic visits will include: 1) a Breathalyzer test (a reading of&#xD;
      zero is necessary for subjects to give informed consent); 2) vital sign measures and a CIWA&#xD;
      (Clinical Institute Withdrawal Assessment for Alcohol) scale score (subjects must not be in&#xD;
      significant withdrawal when they give informed consent and undergo screening evaluations); 3)&#xD;
      urine collection to test for addictive substances and pregnancy; 4) completion of the Time&#xD;
      Line Follow Back (TLFB) interview to determine how many standard drinks have been consumed&#xD;
      during the previous 90 days; 5) interview using the Structured Clinical Interview for DSM-IV&#xD;
      (SCID). Alcohol use module to confirm subjects meet DSM-IV TR criteria for alcohol&#xD;
      dependence; 6) completion of the MINI International Neuropsychiatic Interview (MINI)&#xD;
      diagnostic sections on substance use disorders, psychotic disorders, bipolar disorder, and&#xD;
      eating disorders; 7) subject completion of the Penn Alcohol Craving Scale (PACS); 8) subject&#xD;
      completion of the Spielberger State-Trait Anxiety Inventory (SSTAI); 9) physical examination&#xD;
      by a study doctor; 10) blood collection for laboratory tests.&#xD;
&#xD;
      During the randomization clinic visit, subjects who screen into the study will be randomly&#xD;
      assigned (like the flip of a coin) to receive either oxytocin or placebo intranasal spray.&#xD;
      Members of the researcher staff will instruct subjects in how to self-administer intranasal&#xD;
      spray doses from a spray bottle. Subjects will then take their first intranasal test dose&#xD;
      during a clinic visit scheduled shortly after this screening visit. Subjects will take an&#xD;
      intranasal spray bottle home with them after this visit and continue to self-administer&#xD;
      intranasal test doses three time each day (at approximately breakfast, lunch and dinner time)&#xD;
      for two days and thereafter will take intranasal test doses twice each day (at approximately&#xD;
      breakfast and dinner time). Each dose will be 10 sprays into their nose (5 per nostril&#xD;
      alternating between nostrils).&#xD;
&#xD;
      Procedures during subsequent outpatient clinic visits will include: 1) a Breathalyzer&#xD;
      reading; 2) vital signs and a CIWA score; 3) a TLFB interview; 4) PACS self-rating; 5) State&#xD;
      portion of the SSTAI (SSAI) self-rating; 6) at the week 4, 8, and 12 clinic visits, blood and&#xD;
      urine collection for laboratory tests, pregnancy tests and addictive drug screens.&#xD;
&#xD;
      During the randomization clinic visit and each subsequent clinic visit, subjects'&#xD;
      Breathalyzer reading must be less than .04 g/dL for study procedures to be done. If&#xD;
      Breathalyzer readings are higher, the visit will be rescheduled. Also, during each of these&#xD;
      clinic visits, a Medical Management session (special talk therapy for alcohol dependence)&#xD;
      will be conducted with the study doctor before patients are discharged.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 2015</start_date>
  <completion_date type="Actual">September 2016</completion_date>
  <primary_completion_date type="Actual">September 2016</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of Heavy Drinking Days</measure>
    <time_frame>12 weeks</time_frame>
    <description>Mean proportion of days per week, over the 12-week trial, when subjects drank heavily (5 or more standard drinks for men, 4 or more standard drinks for women).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean Weekly Drinks Per Drinking Day</measure>
    <time_frame>12 weeks</time_frame>
    <description>The mean number of standard drinks (the amount of alcohol in a standard drink is roughly equivalent to the amount of alcohol in a 12 ounce beer) consumed by subjects on days when they drank alcoholic beverages each week averaged over the 12-week trial.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Alcohol Craving</measure>
    <time_frame>12 weeks</time_frame>
    <description>Mean weekly Penn Alcohol Craving Scale (PACS) scores.The PACS is a five-item self-administered instrument for assessing craving, frequency, intensity, and duration of thoughts about drinking as well as the ability to resist drinking. Scores range from: Minimum: 0 Maximum: 30 Lower scores are associated with better outcomes.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">22</enrollment>
  <condition>Alcohol Dependence</condition>
  <arm_group>
    <arm_group_label>Active</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intranasal oxytocin doses 2-3 times/day for 12 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Intranasal placebo doses 2-3 times/day for 12 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intranasal Oxytocin</intervention_name>
    <description>10 insufflations (40IU of oxytocin total) given 3 initially then 2 times daily for 12 weeks</description>
    <arm_group_label>Active</arm_group_label>
    <other_name>Syntocinon spray</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>10 insufflations (same solution as active treatment minus oxytocin) given 3 initially and then 2 times daily for 12 weeks</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Meeting criteria for DSM-IV-TR alcohol dependence.&#xD;
&#xD;
          -  Consumption of at least 35 standard drinks/week for men or 28 standard drinks/week for&#xD;
             women for at least 4 consecutive weeks prior to enrollment into the study.&#xD;
&#xD;
          -  Women who are able to conceive children and who are sexually active must be on an&#xD;
             effective form of birth control such as oral contraceptives, IUDs or the use of&#xD;
             condoms with spermicide.&#xD;
&#xD;
          -  Competency to give valid informed consent as indicated by a) a Breathalyzer reading at&#xD;
             the time the consent form is signed showing an estimated blood alcohol level (BAL) of&#xD;
             zero; b) ability to understand the written informed consent form demonstrated by&#xD;
             correctly answering questions about the contents of the form after reading the consent&#xD;
             form without help (this will also determine whether prospective subjects can read and&#xD;
             understand the study questionnaires).&#xD;
&#xD;
          -  Ability to get to appointments either through personal or public transportation.&#xD;
&#xD;
          -  Ages 18-65.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of alcohol withdrawal-related seizures, delirium tremens or hallucinations.&#xD;
&#xD;
          -  Clinically significant medical disease that might interfere with the evaluation of the&#xD;
             study medication or present a safety concern (e.g., renal insufficiency, cirrhosis,&#xD;
             unstable hypertension, unstable diabetes mellitus, seizure disorder).&#xD;
&#xD;
          -  History of psychotic disorder or admission for mania, meeting criteria for an eating&#xD;
             disorder in the last 2 years, current moderate or severe major depression, current&#xD;
             suicidal ideation.&#xD;
&#xD;
          -  Currently meeting DSM-IV TR criteria for dependence on addictive substances other than&#xD;
             alcohol except for nicotine or caffeine. Substance abuse disorders are not&#xD;
             exclusionary.&#xD;
&#xD;
          -  Consumption during the week prior to enrollment or plans to consume during the 12-week&#xD;
             trial of benzodiazepines, barbiturates, anticonvulsants or stimulants.&#xD;
&#xD;
          -  AST or ALT &gt; 5 times ULN, bilirubin &gt; 1.5 X ULN, sodium &lt; 132 or &gt; 150 mMol/L,&#xD;
             potassium &lt; 3.2 or &gt; 5.3 mMol/L.&#xD;
&#xD;
          -  Women who are pregnant or breastfeeding.&#xD;
&#xD;
          -  Currently participating in or intent to participate in an additional alcohol treatment&#xD;
             program during the study period other than Alcoholics Anonymous.&#xD;
&#xD;
          -  Court-mandated participation in alcohol treatment or pending incarceration.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Cort A Pedersen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of North Carolina, Chapel Hill</affiliation>
  </overall_official>
  <overall_official>
    <last_name>James C Garbutt, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of North Carolina, Chapel Hill</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of North Carolina at Chapel Hill</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>September 25, 2014</study_first_submitted>
  <study_first_submitted_qc>September 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 29, 2014</study_first_posted>
  <results_first_submitted>May 23, 2017</results_first_submitted>
  <results_first_submitted_qc>July 14, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">August 15, 2017</results_first_posted>
  <last_update_submitted>July 14, 2017</last_update_submitted>
  <last_update_submitted_qc>July 14, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 15, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Alcohol dependence</keyword>
  <keyword>Alcohol</keyword>
  <keyword>Oxytocin</keyword>
  <keyword>Intranasal administration</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alcoholism</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>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Active</title>
          <description>Intranasal oxytocin doses 2-3 times/day for 12 weeks&#xD;
Intranasal Oxytocin: 10 insufflations (40IU of oxytocin total) given 3 initially then 2 times daily for 12 weeks</description>
        </group>
        <group group_id="P2">
          <title>Control</title>
          <description>Intranasal placebo doses 2-3 times/day for 12 weeks&#xD;
Placebo: 10 insufflations (same solution as active treatment minus oxytocin) given 3 initially and then 2 times daily for 12 weeks</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</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>Active</title>
          <description>Intranasal oxytocin doses 2-3 times/day for 12 weeks&#xD;
Intranasal Oxytocin: 10 insufflations (40IU of oxytocin total) given 3 initially then 2 times daily for 12 weeks</description>
        </group>
        <group group_id="B2">
          <title>Control</title>
          <description>Intranasal placebo doses 2-3 times/day for 12 weeks&#xD;
Placebo: 10 insufflations (same solution as active treatment minus oxytocin) given 3 initially and then 2 times daily for 12 weeks</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="12"/>
            <count group_id="B2" value="10"/>
            <count group_id="B3" value="22"/>
          </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="12"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 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_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="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="13"/>
                  </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="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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>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>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Proportion of Heavy Drinking Days</title>
        <description>Mean proportion of days per week, over the 12-week trial, when subjects drank heavily (5 or more standard drinks for men, 4 or more standard drinks for women).</description>
        <time_frame>12 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Active</title>
            <description>Intranasal oxytocin doses 2-3 times/day for 12 weeks&#xD;
Intranasal Oxytocin: 10 insufflations (40IU of oxytocin total) given 3 initially then 2 times daily for 12 weeks</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Intranasal placebo doses 2-3 times/day for 12 weeks&#xD;
Placebo: 10 insufflations (same solution as active treatment minus oxytocin) given 3 initially and then 2 times daily for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Heavy Drinking Days</title>
          <description>Mean proportion of days per week, over the 12-week trial, when subjects drank heavily (5 or more standard drinks for men, 4 or more standard drinks for women).</description>
          <units>proportion of days per week</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.3072" spread="0.094"/>
                    <measurement group_id="O2" value="0.5914" spread="0.1024"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Mean Weekly Drinks Per Drinking Day</title>
        <description>The mean number of standard drinks (the amount of alcohol in a standard drink is roughly equivalent to the amount of alcohol in a 12 ounce beer) consumed by subjects on days when they drank alcoholic beverages each week averaged over the 12-week trial.</description>
        <time_frame>12 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Active</title>
            <description>Intranasal oxytocin doses 2-3 times/day for 12 weeks&#xD;
Intranasal Oxytocin: 10 insufflations (40IU of oxytocin total) given 3 initially then 2 times daily for 12 weeks</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Intranasal placebo doses 2-3 times/day for 12 weeks&#xD;
Placebo: 10 insufflations (same solution as active treatment minus oxytocin) given 3 initially and then 2 times daily for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Weekly Drinks Per Drinking Day</title>
          <description>The mean number of standard drinks (the amount of alcohol in a standard drink is roughly equivalent to the amount of alcohol in a 12 ounce beer) consumed by subjects on days when they drank alcoholic beverages each week averaged over the 12-week trial.</description>
          <units>number of drinks per drinking day</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.8929" spread="0.5868"/>
                    <measurement group_id="O2" value="7.5621" spread="0.6108"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Alcohol Craving</title>
        <description>Mean weekly Penn Alcohol Craving Scale (PACS) scores.The PACS is a five-item self-administered instrument for assessing craving, frequency, intensity, and duration of thoughts about drinking as well as the ability to resist drinking. Scores range from: Minimum: 0 Maximum: 30 Lower scores are associated with better outcomes.</description>
        <time_frame>12 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Active</title>
            <description>Intranasal oxytocin doses 2-3 times/day for 12 weeks&#xD;
Intranasal Oxytocin: 10 insufflations (40IU of oxytocin total) given 3 initially then 2 times daily for 12 weeks</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Intranasal placebo doses 2-3 times/day for 12 weeks&#xD;
Placebo: 10 insufflations (same solution as active treatment minus oxytocin) given 3 initially and then 2 times daily for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Alcohol Craving</title>
          <description>Mean weekly Penn Alcohol Craving Scale (PACS) scores.The PACS is a five-item self-administered instrument for assessing craving, frequency, intensity, and duration of thoughts about drinking as well as the ability to resist drinking. Scores range from: Minimum: 0 Maximum: 30 Lower scores are associated with better outcomes.</description>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.8481" spread="2.1254"/>
                    <measurement group_id="O2" value="12.6685" spread="2.3122"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Active</title>
          <description>Intranasal oxytocin doses 2-3 times/day for 12 weeks&#xD;
Intranasal Oxytocin: 10 insufflations (40IU of oxytocin total) given 3 initially then 2 times daily for 12 weeks</description>
        </group>
        <group group_id="E2">
          <title>Control</title>
          <description>Intranasal placebo doses 2-3 times/day for 12 weeks&#xD;
Placebo: 10 insufflations (same solution as active treatment minus oxytocin) given 3 initially and then 2 times daily for 12 weeks</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="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-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="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>sore throat</sub_title>
                <description>backflow of intranasal spray down the throat was reported to cause soreness in the pharyngeal area</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>nosebleed</sub_title>
                <description>a nosebleed associated with repeated intranasal administration of test substance that did not recur after subject stopped intranasal doses</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </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>Dr. Cort Pedersen</name_or_title>
      <organization>University of North Carolina at Chapel Hill</organization>
      <phone>919-923-3284</phone>
      <email>cort_pedersen@med.unc.edu</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02251912
org study id: 12-1862b
secondary id: 1R21AA021927-01A1
nct id: NCT02251912
lead sponsor: 
collaborator: 
has dmc: No
Purpose: Test whether oxytocin treatment decreases drinking in people who have been consuming
      alcohol heavily for long periods and are physically and psychologically dependent on alcohol.

      Participants: 50 adults with alcohol dependence

      Procedures (methods): Oxytocin or placebo will be administered three times a day for the
      first 2 days followed by twice daily intranasal doses for the rest of the 12 weeks. Before,
      during and at the end of the trial, each subject will undergo evaluations including
      breathalyzer readings, rating withdrawal symptoms, interviews about amount of alcohol
      consumed since last clinic visit, subject self-ratings of anxiety, alcohol craving and, at
      some visits, laboratory measures (blood and urine) to monitor safety and alcohol/drug use.
      Following the active phase of the trial, subjects will be followed up at 4 weeks and 12 weeks
      to evaluate for post-medication safety and efficacy
The purpose of this research study is to learn whether oxytocin treatment decreases drinking
      and alcohol craving in people who have been consuming alcohol heavily for long periods and
      are unable to stop drinking on their own. Oxytocin is made naturally and is released in parts
      of the brain where it acts like a chemical signal from one cell to another. Oxytocin is
      approved by the Food and Drug Administration for stimulating labor in pregnant women but is
      not approved as a treatment to decrease alcohol drinking.

      People who drink large amounts of alcohol every day or many days per week for weeks or months
      undergo chemical changes in their brains. They continue to drink frequently and heavily
      because, even though they may know drinking is not good for their health, they experience
      unpleasant symptoms if they stop or decrease drinking. Those symptoms can include increased
      anxiety, difficulty sleeping, difficulty tolerating stress, mild to moderate withdrawal
      symptoms such as tremors, nausea, feeling sweaty and/or headaches, and cravings to drink.
      Studies found that giving oxytocin to alcohol-addicted animals reduced symptoms when they
      were put into alcohol withdrawal. A pilot study conducted at UNC found that twice daily
      intranasal doses of oxytocin decreased withdrawal symptoms in heavy drinkers who were
      admitted to a hospital for medical detoxification to come off alcohol.

      This study will test whether daily intranasal oxytocin treatment for 12 weeks will decrease
      how much subjects drink as well as craving for alcohol and anxiety.

      Prospective subjects must have been drinking large amounts of alcohol for a sustained period
      to qualify for this study and want help to stop or cut back on their drinking. Subjects will
      self-administer oxytocin or placebo in this study in an intranasal spray. The placebo spray
      contains all of the ingredients of the oxytocin spray EXCEPT oxytocin. Subjects' assignment
      to oxytocin or placebo treatment will be random (like a flip of a coin).

      Subjects must sign a consent form to take part in this study. Their participation in the
      study will last up to 14-15 weeks. Prospective subjects will be recruited from the community
      through advertisements (radio, social media, mass emails, etc). Those who respond to
      advertisements will undergo initial screening over the phone. Prospective subjects who appear
      to meet study criteria based on the phone screen will give informed consent and undergo more
      detailed evaluation during a screening clinic visit. If they are found to meet study
      criteria, they will shortly thereafter attend another clinic visit (randomization clinic
      visit) during which they will be randomized to oxytocin or placebo treatment and take their
      first test dose under study personnel supervision. They will then take home the bottle
      contained the intranasal study medication to which they have been randomized and
      self-administer intranasal test doses at home for the remainder of the 12-week test treatment
      period. New intranasal spray bottles will be exchanged for old every 2 weeks. Subjects will
      attend 8 additional clinic visits over a 12 week period after the randomization clinic visit.
      Each clinic visit will last 1-2 hours.

      Procedures during screening clinic visits will include: 1) a Breathalyzer test (a reading of
      zero is necessary for subjects to give informed consent); 2) vital sign measures and a CIWA
      (Clinical Institute Withdrawal Assessment for Alcohol) scale score (subjects must not be in
      significant withdrawal when they give informed consent and undergo screening evaluations); 3)
      urine collection to test for addictive substances and pregnancy; 4) completion of the Time
      Line Follow Back (TLFB) interview to determine how many standard drinks have been consumed
      during the previous 90 days; 5) interview using the Structured Clinical Interview for DSM-IV
      (SCID). Alcohol use module to confirm subjects meet DSM-IV TR criteria for alcohol
      dependence; 6) completion of the MINI International Neuropsychiatic Interview (MINI)
      diagnostic sections on substance use disorders, psychotic disorders, bipolar disorder, and
      eating disorders; 7) subject completion of the Penn Alcohol Craving Scale (PACS); 8) subject
      completion of the Spielberger State-Trait Anxiety Inventory (SSTAI); 9) physical examination
      by a study doctor; 10) blood collection for laboratory tests.

      During the randomization clinic visit, subjects who screen into the study will be randomly
      assigned (like the flip of a coin) to receive either oxytocin or placebo intranasal spray.
      Members of the researcher staff will instruct subjects in how to self-administer intranasal
      spray doses from a spray bottle. Subjects will then take their first intranasal test dose
      during a clinic visit scheduled shortly after this screening visit. Subjects will take an
      intranasal spray bottle home with them after this visit and continue to self-administer
      intranasal test doses three time each day (at approximately breakfast, lunch and dinner time)
      for two days and thereafter will take intranasal test doses twice each day (at approximately
      breakfast and dinner time). Each dose will be 10 sprays into their nose (5 per nostril
      alternating between nostrils).

      Procedures during subsequent outpatient clinic visits will include: 1) a Breathalyzer
      reading; 2) vital signs and a CIWA score; 3) a TLFB interview; 4) PACS self-rating; 5) State
      portion of the SSTAI (SSAI) self-rating; 6) at the week 4, 8, and 12 clinic visits, blood and
      urine collection for laboratory tests, pregnancy tests and addictive drug screens.

      During the randomization clinic visit and each subsequent clinic visit, subjects'
      Breathalyzer reading must be less than .04 g/dL for study procedures to be done. If
      Breathalyzer readings are higher, the visit will be rescheduled. Also, during each of these
      clinic visits, a Medical Management session (special talk therapy for alcohol dependence)
      will be conducted with the study doctor before patients are discharged.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Proportion of Heavy Drinking Days
time frame: 12 weeks
description: Mean proportion of days per week, over the 12-week trial, when subjects drank heavily (5 or more standard drinks for men, 4 or more standard drinks for women).
measure: Mean Weekly Drinks Per Drinking Day
time frame: 12 weeks
description: The mean number of standard drinks (the amount of alcohol in a standard drink is roughly equivalent to the amount of alcohol in a 12 ounce beer) consumed by subjects on days when they drank alcoholic beverages each week averaged over the 12-week trial.
measure: Alcohol Craving
time frame: 12 weeks
description: Mean weekly Penn Alcohol Craving Scale (PACS) scores.The PACS is a five-item self-administered instrument for assessing craving, frequency, intensity, and duration of thoughts about drinking as well as the ability to resist drinking. Scores range from: Minimum: 0 Maximum: 30 Lower scores are associated with better outcomes.
arm group label: Active
arm group type: Experimental
description: Intranasal oxytocin doses 2-3 times/day for 12 weeks
arm group label: Control
arm group type: Placebo Comparator
description: Intranasal placebo doses 2-3 times/day for 12 weeks
intervention type: Drug
intervention name: Intranasal Oxytocin
description: 10 insufflations (40IU of oxytocin total) given 3 initially then 2 times daily for 12 weeks
arm group label: Active
other name: Syntocinon spray
intervention type: Drug
intervention name: Placebo
description: 10 insufflations (same solution as active treatment minus oxytocin) given 3 initially and then 2 times daily for 12 weeks
arm group label: Control
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Cort A Pedersen, MD
role: Principal Investigator
affiliation: University of North Carolina, Chapel Hill
last name: James C Garbutt, MD
role: Principal Investigator
affiliation: University of North Carolina, Chapel Hill
facility: 
country: United States
responsible party type: Sponsor
mesh term: Alcoholism
mesh term: Oxytocin
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 