<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/NCT02255357</url>
  </required_header>
  <id_info>
    <org_study_id>#6933</org_study_id>
    <secondary_id>DA035461-01A1</secondary_id>
    <nct_id>NCT02255357</nct_id>
  </id_info>
  <brief_title>Investigation of Intranasal Oxytocin on Relapse Risk in Cocaine-dependent Patients.</brief_title>
  <official_title>Investigation of the Effect of Intranasal Oxytocin on Relapse Risk in Cocaine-dependent Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>New York State Psychiatric Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>New York State Psychiatric Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This proposal describes a combined laboratory and clinical trial preliminary investigation to&#xD;
      advance medication development for cocaine dependence. The main objective is to test whether&#xD;
      intranasal Oxytocin could reduce relapse risk by reducing stress sensitivity. To measure the&#xD;
      stress sensitivity, this study will evaluate a new stress challenge: a) Intranasal&#xD;
      desmopressin, a vasopressin analog, will be used an endocrine stressor; its effects will be&#xD;
      evaluated by serial measurements of serum Adrenocorticotropin hormone (ACTH), and self&#xD;
      reports; b) if pretreatment with intranasal oxytocin dampens the ACTH and subjective response&#xD;
      to intranasal desmopressin. These measures will be tested during a 7-day inpatient abstinence&#xD;
      induction hospitalization. For those patients with family and work obligations, an outpatient&#xD;
      abstinence induction procedure is available. The response to the desmopressin challenge will&#xD;
      be compared to a cohort of matched control subjects. After abstinence induction, cocaine&#xD;
      dependent patients enter a 6-week, double blind, randomized, placebo-controlled trial of 24&#xD;
      IU of intranasal oxytocin vs. placebo, to monitor if this reduces the relapse risk.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is based on the findings that chronic stress, caused in these patients by cocaine&#xD;
      dependence, increases the sensitivity of the Hypothalamo-Pituitary-Adrenal (HPA) axis and CNS&#xD;
      stress pathways to vasopressin. For their part, oxytocin systems, in chronic stress, acquire&#xD;
      an increasing moderating effect on CNS stress system and the HPA axis. Cocaine dependence&#xD;
      generates increased responsivity of stress system to oxytocin in the face of depleted&#xD;
      oxytocin stores; thus creating an environment where exogenous oxytocin could exert a strong&#xD;
      regulatory effect. Intranasal administration provides a convenient method to deliver these&#xD;
      small peptides to the brain. Studying the feasibility of this approach, and its applicability&#xD;
      to the treatment of cocaine-dependent patients, will be a goal of the study. The main outcome&#xD;
      of this study will be the number of consecutive days of abstinence from cocaine after&#xD;
      abstinence induction. A secondary outcome will be: Is the acute effect of intranasal oxytocin&#xD;
      on desmopressin-induced ACTH secretion associated with the number of days of continued&#xD;
      abstinence.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2015</start_date>
  <completion_date type="Actual">February 14, 2018</completion_date>
  <primary_completion_date type="Actual">February 14, 2018</primary_completion_date>
  <phase>Phase 2/Phase 3</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>Weeks of Abstinence From Cocaine</measure>
    <time_frame>Phase 1: 7 days; Phase 2: 6 weeks</time_frame>
    <description>this is outcome for the phase 2, clinicial trial portion of this combined laboratory and clinical trial laboratory human study&#xD;
For the human laboratory study, Phase 1, the primary outcome is differences in ACTH levels following a) Intranasal Desmopressin, and, on a consecutive day, b) Intranasal Desmopressin preceded by a treatment with Intranasal Oxytocin (Syntocinon). this takes place on 2 consecutive days</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">43</enrollment>
  <condition>Cocaine Dependence</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Solution containing only the excipients of the original solution without Oxytocin.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intranasal Syntocinon</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intranasal Oxytocin 24 IU per day.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Solution containing only the excipients of the original solution without Oxytocin.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intranasal Oxytocin</intervention_name>
    <description>solution containing Oxytocin 6 IU/0.1cc or per puff is used in this arm</description>
    <arm_group_label>Intranasal Syntocinon</arm_group_label>
    <other_name>Syntocinon</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Study Inclusion Criteria (cocaine-dependent participants):&#xD;
&#xD;
          -  Age 18 to 60.&#xD;
&#xD;
          -  Meet DSM-IV criteria for current cocaine dependence and is seeking treatment.&#xD;
&#xD;
          -  Displays at least one cocaine-positive urine toxicology during screening.&#xD;
&#xD;
          -  Use of cocaine at least 4 days in the past month, with at least weekly use, or reports&#xD;
             episodic binges of large amounts of cocaine (at least $200) at least 2x/month.&#xD;
&#xD;
          -  Able to give informed consent and comply with study procedures.&#xD;
&#xD;
          -  Can pass the blindfolded scent test recognizing the scent of cinnamon or coffee.&#xD;
&#xD;
        Study Exclusion Criteria (cocaine-dependent participants):&#xD;
&#xD;
          -  Meets DSM-IV criteria for bipolar disorder, schizophrenia or any psychotic disorder&#xD;
             other than transient psychosis due to drug abuse. Severe depression is an exclusion&#xD;
             criteria (Hamilton Depression Scale ≥ 15).&#xD;
&#xD;
          -  History of allergy or adverse event related to Oxytocin or Desmopressin. Patient using&#xD;
             Oxytocin or Vasopressin-based products cannot participate.&#xD;
&#xD;
          -  Chronic organic mental disorder, insufficient proficiency in English, or any condition&#xD;
             or status (illiteracy) that would render an individual incapable of giving informed&#xD;
             consent.&#xD;
&#xD;
          -  Significant current suicidal risk, suicide attempt within the past year.&#xD;
&#xD;
          -  Unstable physical disorders, which might make participation hazardous.&#xD;
&#xD;
          -  Coronary Vascular disease as indicated by history, or suspected by abnormal ECG.&#xD;
&#xD;
          -  Currently meets DSM-IV criteria for another substance dependence or abuse disorder&#xD;
             other than nicotine, or alcohol. If alcohol dependent, must not be in need of&#xD;
             detoxification.&#xD;
&#xD;
          -  Participants who cannot comply with study procedures during the inpatient or&#xD;
             outpatient abstinence induction (phase 1) will not proceed to Phase 2.&#xD;
&#xD;
          -  Pregnancy, positive urine pregnancy test, or breastfeeding. Women who wish to&#xD;
             participate must agree to use a method of contraception during the study and sign a&#xD;
             written commitment to that effect, and submit to a urine pregnancy test every two&#xD;
             weeks of Phase 2.&#xD;
&#xD;
          -  History of transphenoidal surgery or sinus surgery in the past month. Simple nasal&#xD;
             congestion is not exclusionary.&#xD;
&#xD;
        Study Inclusion Criteria (healthy volunteers):&#xD;
&#xD;
          -  Age 18 to 60.&#xD;
&#xD;
          -  Able to give informed consent and comply with study procedures.&#xD;
&#xD;
          -  Can pass the blindfolded scent test recognizing the scent of cinnamon or coffee.&#xD;
&#xD;
        Study Exclusion Criteria (healthy volunteers):&#xD;
&#xD;
          -  DSM-IV Axis 1 psychiatric diagnosis. Severe Major Depression (Hamilton Depression&#xD;
             Scale &gt; 15) is an exclusion criteria.&#xD;
&#xD;
          -  Unstable physical disorders, which might make participation hazardous.&#xD;
&#xD;
          -  Diagnosis of Substance Abuse or Dependence disorder, with exception of nicotine&#xD;
             dependence. Patients in remission may participate if its duration is greater than 2&#xD;
             years preceding participation.&#xD;
&#xD;
          -  History of allergy or adverse event related to oxytocin or desmopressin. Patient using&#xD;
             oxytocin or vasopressin-based products cannot participate.&#xD;
&#xD;
          -  Chronic organic mental disorder, insufficient proficiency in English or illiteracy&#xD;
             that would render an individual incapable of giving informed consent.&#xD;
&#xD;
          -  History of transphenoidal surgery or sinus surgery in the past month. Simple nasal&#xD;
             congestion is not exclusionary.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wilfrid N Raby, PhD, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Division of Substance Abuse, Department of Psychiatry - Columbia university</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Divison on Substance Abuse - Albert Einstein College of Medicine</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Substance Treatment and Research Service (STARS)</name>
      <address>
        <city>Manhattan</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.pdr.net/drug-summary/pitocin?druglabelid=1666&amp;mode=preview</url>
    <description>Oxytocin description</description>
  </link>
  <link>
    <url>http://www.pdr.net/drug-summary/ddavp-nasal-spray?druglabelid=1034&amp;mode=preview</url>
    <description>Desmopressin Acetate description</description>
  </link>
  <reference>
    <citation>Araya AV, Rojas P, Fritsch R, Rojas R, Herrera L, Rojas G, Gatica H, Silva H, Fiedler JL. Early response to venlafaxine antidepressant correlates with lower ACTH levels prior to pharmacological treatment. Endocrine. 2006 Dec;30(3):289-98. doi: 10.1007/s12020-006-0007-2.</citation>
    <PMID>17526941</PMID>
  </reference>
  <reference>
    <citation>Manning M, Stoev S, Chini B, Durroux T, Mouillac B, Guillon G. Peptide and non-peptide agonists and antagonists for the vasopressin and oxytocin V1a, V1b, V2 and OT receptors: research tools and potential therapeutic agents. Prog Brain Res. 2008;170:473-512. doi: 10.1016/S0079-6123(08)00437-8.</citation>
    <PMID>18655903</PMID>
  </reference>
  <reference>
    <citation>Rodrigues SM, Saslow LR, Garcia N, John OP, Keltner D. Oxytocin receptor genetic variation relates to empathy and stress reactivity in humans. Proc Natl Acad Sci U S A. 2009 Dec 15;106(50):21437-41. doi: 10.1073/pnas.0909579106. Epub 2009 Nov 23.</citation>
    <PMID>19934046</PMID>
  </reference>
  <reference>
    <citation>Suzuki Y, Yamamoto S, Umegaki H, Onishi J, Mogi N, Fujishiro H, Iguchi A. Smell identification test as an indicator for cognitive impairment in Alzheimer's disease. Int J Geriatr Psychiatry. 2004 Aug;19(8):727-33. doi: 10.1002/gps.1161.</citation>
    <PMID>15290695</PMID>
  </reference>
  <reference>
    <citation>Weiss RD, Griffin ML, Hufford C, Muenz LR, Najavits LM, Jansson SB, Kogan J, Thompson HJ. Early prediction of initiation of abstinence from cocaine. Use of a craving questionnaire. Am J Addict. 1997 Summer;6(3):224-31.</citation>
    <PMID>9256988</PMID>
  </reference>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>September 30, 2014</study_first_submitted>
  <study_first_submitted_qc>September 30, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 2, 2014</study_first_posted>
  <results_first_submitted>August 9, 2019</results_first_submitted>
  <results_first_submitted_qc>November 21, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">November 29, 2019</results_first_posted>
  <last_update_submitted>June 2, 2023</last_update_submitted>
  <last_update_submitted_qc>June 2, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 5, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>New York State Psychiatric Institute</investigator_affiliation>
    <investigator_full_name>Wilfrid Raby</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Oxytocin</keyword>
  <keyword>Vasopressin</keyword>
  <keyword>Cocaine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cocaine-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>September 29, 2014</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/57/NCT02255357/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 15, 2013</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/57/NCT02255357/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>For control participants, reasons for not being included in the final analysis included: 1) not completing the laboratory protocol (phase 1) the only portion of the study that they participated in. 2 did not complete, and 1 was excluded for medical complication during the laboratory challenge.&#xD;
For Cocaine use disorder patients, reasons for not included in the analysis or not counting as completers: 1) droping out after the initial inpatient laboratory phase;</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>Solution containing only the excipients of the original solution without Oxytocin.&#xD;
Placebo: Solution containing only the excipients of the original solution without Oxytocin.</description>
        </group>
        <group group_id="P2">
          <title>Intranasal Syntocinon</title>
          <description>Intranasal Oxytocin 24 IU per day.&#xD;
Intranasal Oxytocin: solution containing Oxytocin 6 IU/0.1cc or per puff is used in this arm</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="29"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="24"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="24"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Placebo patients receive IN placebo solution, 2 insufflations per nostril, those randomized to Intranasal Oxytocin receive daily insufflation of 24 IU, or 2 insuflations per nostril.</population>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>Solution containing only the excipients of the original solution without Oxytocin.&#xD;
Placebo: Solution containing only the excipients of the original solution without Oxytocin.</description>
        </group>
        <group group_id="B2">
          <title>Intranasal Syntocinon</title>
          <description>Intranasal Oxytocin 24 IU per day.&#xD;
Intranasal Oxytocin: solution containing Oxytocin 6 IU/0.1cc or per puff is used in this arm</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="14"/>
            <count group_id="B2" value="29"/>
            <count group_id="B3" value="43"/>
          </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="14"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="43"/>
                  </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="3"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="30"/>
                  </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="13"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="40"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</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>More than one race</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>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="14"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Weeks of Abstinence From Cocaine</title>
        <description>this is outcome for the phase 2, clinicial trial portion of this combined laboratory and clinical trial laboratory human study&#xD;
For the human laboratory study, Phase 1, the primary outcome is differences in ACTH levels following a) Intranasal Desmopressin, and, on a consecutive day, b) Intranasal Desmopressin preceded by a treatment with Intranasal Oxytocin (Syntocinon). this takes place on 2 consecutive days</description>
        <time_frame>Phase 1: 7 days; Phase 2: 6 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Placebo for Phase 2, Clinical Trial</title>
            <description>Solution containing only the excipients of the original solution without Oxytocin.&#xD;
Placebo: Solution containing only the excipients of the original solution without Oxytocin.</description>
          </group>
          <group group_id="O2">
            <title>Intranasal Syntocinon for Clinical Trial Phase 2</title>
            <description>Intranasal Oxytocin 24 IU per day.&#xD;
Intranasal Oxytocin: solution containing Oxytocin 6 IU/0.1cc or per puff is used in this arm</description>
          </group>
        </group_list>
        <measure>
          <title>Weeks of Abstinence From Cocaine</title>
          <description>this is outcome for the phase 2, clinicial trial portion of this combined laboratory and clinical trial laboratory human study&#xD;
For the human laboratory study, Phase 1, the primary outcome is differences in ACTH levels following a) Intranasal Desmopressin, and, on a consecutive day, b) Intranasal Desmopressin preceded by a treatment with Intranasal Oxytocin (Syntocinon). this takes place on 2 consecutive days</description>
          <units>weeks</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" lower_limit="1.0" upper_limit="2.0"/>
                    <measurement group_id="O2" value="1.0" lower_limit="1.0" upper_limit="1.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>6 months during randomized trial or participants length of participation</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>Solution containing only the excipients of the original solution without Oxytocin.&#xD;
Placebo: Solution containing only the excipients of the original solution without Oxytocin.</description>
        </group>
        <group group_id="E2">
          <title>Intranasal Syntocinon</title>
          <description>Intranasal Oxytocin 24 IU per day.&#xD;
Intranasal Oxytocin: solution containing Oxytocin 6 IU/0.1cc or per puff is used in this arm</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="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
              </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="6" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>feeling woozy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>headache</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>feeling energized</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>less irritable</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>calm</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </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>wilfrid raby, m.d.</name_or_title>
      <organization>new york psychiatric institute</organization>
      <phone>2129233031</phone>
      <email>wilfrid.raby@nyspi.columbia.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/NCT02255357
org study id: #6933
secondary id: DA035461-01A1
nct id: NCT02255357
lead sponsor: 
has dmc: Yes
This proposal describes a combined laboratory and clinical trial preliminary investigation to
      advance medication development for cocaine dependence. The main objective is to test whether
      intranasal Oxytocin could reduce relapse risk by reducing stress sensitivity. To measure the
      stress sensitivity, this study will evaluate a new stress challenge: a) Intranasal
      desmopressin, a vasopressin analog, will be used an endocrine stressor; its effects will be
      evaluated by serial measurements of serum Adrenocorticotropin hormone (ACTH), and self
      reports; b) if pretreatment with intranasal oxytocin dampens the ACTH and subjective response
      to intranasal desmopressin. These measures will be tested during a 7-day inpatient abstinence
      induction hospitalization. For those patients with family and work obligations, an outpatient
      abstinence induction procedure is available. The response to the desmopressin challenge will
      be compared to a cohort of matched control subjects. After abstinence induction, cocaine
      dependent patients enter a 6-week, double blind, randomized, placebo-controlled trial of 24
      IU of intranasal oxytocin vs. placebo, to monitor if this reduces the relapse risk.
This study is based on the findings that chronic stress, caused in these patients by cocaine
      dependence, increases the sensitivity of the Hypothalamo-Pituitary-Adrenal (HPA) axis and CNS
      stress pathways to vasopressin. For their part, oxytocin systems, in chronic stress, acquire
      an increasing moderating effect on CNS stress system and the HPA axis. Cocaine dependence
      generates increased responsivity of stress system to oxytocin in the face of depleted
      oxytocin stores; thus creating an environment where exogenous oxytocin could exert a strong
      regulatory effect. Intranasal administration provides a convenient method to deliver these
      small peptides to the brain. Studying the feasibility of this approach, and its applicability
      to the treatment of cocaine-dependent patients, will be a goal of the study. The main outcome
      of this study will be the number of consecutive days of abstinence from cocaine after
      abstinence induction. A secondary outcome will be: Is the acute effect of intranasal oxytocin
      on desmopressin-induced ACTH secretion associated with the number of days of continued
      abstinence.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Weeks of Abstinence From Cocaine
time frame: Phase 1: 7 days; Phase 2: 6 weeks
description: this is outcome for the phase 2, clinicial trial portion of this combined laboratory and clinical trial laboratory human study
For the human laboratory study, Phase 1, the primary outcome is differences in ACTH levels following a) Intranasal Desmopressin, and, on a consecutive day, b) Intranasal Desmopressin preceded by a treatment with Intranasal Oxytocin (Syntocinon). this takes place on 2 consecutive days
arm group label: Placebo
arm group type: Placebo Comparator
description: Solution containing only the excipients of the original solution without Oxytocin.
arm group label: Intranasal Syntocinon
arm group type: Active Comparator
description: Intranasal Oxytocin 24 IU per day.
intervention type: Drug
intervention name: Placebo
description: Solution containing only the excipients of the original solution without Oxytocin.
arm group label: Placebo
intervention type: Drug
intervention name: Intranasal Oxytocin
description: solution containing Oxytocin 6 IU/0.1cc or per puff is used in this arm
arm group label: Intranasal Syntocinon
other name: Syntocinon
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Wilfrid N Raby, PhD, MD
role: Principal Investigator
affiliation: Division of Substance Abuse, Department of Psychiatry - Columbia university
facility: 
facility: 
country: United States
url: http://www.pdr.net/drug-summary/pitocin?druglabelid=1666&mode=preview
description: Oxytocin description
url: http://www.pdr.net/drug-summary/ddavp-nasal-spray?druglabelid=1034&mode=preview
description: Desmopressin Acetate description
citation: Araya AV, Rojas P, Fritsch R, Rojas R, Herrera L, Rojas G, Gatica H, Silva H, Fiedler JL. Early response to venlafaxine antidepressant correlates with lower ACTH levels prior to pharmacological treatment. Endocrine. 2006 Dec;30(3):289-98. doi: 10.1007/s12020-006-0007-2.
PMID: 17526941
citation: Manning M, Stoev S, Chini B, Durroux T, Mouillac B, Guillon G. Peptide and non-peptide agonists and antagonists for the vasopressin and oxytocin V1a, V1b, V2 and OT receptors: research tools and potential therapeutic agents. Prog Brain Res. 2008;170:473-512. doi: 10.1016/S0079-6123(08)00437-8.
PMID: 18655903
citation: Rodrigues SM, Saslow LR, Garcia N, John OP, Keltner D. Oxytocin receptor genetic variation relates to empathy and stress reactivity in humans. Proc Natl Acad Sci U S A. 2009 Dec 15;106(50):21437-41. doi: 10.1073/pnas.0909579106. Epub 2009 Nov 23.
PMID: 19934046
citation: Suzuki Y, Yamamoto S, Umegaki H, Onishi J, Mogi N, Fujishiro H, Iguchi A. Smell identification test as an indicator for cognitive impairment in Alzheimer's disease. Int J Geriatr Psychiatry. 2004 Aug;19(8):727-33. doi: 10.1002/gps.1161.
PMID: 15290695
citation: Weiss RD, Griffin ML, Hufford C, Muenz LR, Najavits LM, Jansson SB, Kogan J, Thompson HJ. Early prediction of initiation of abstinence from cocaine. Use of a craving questionnaire. Am J Addict. 1997 Summer;6(3):224-31.
PMID: 9256988
responsible party type: Principal Investigator
investigator affiliation: New York State Psychiatric Institute
investigator full name: Wilfrid Raby
investigator title: Principal Investigator
mesh term: Cocaine-Related Disorders
mesh term: Oxytocin
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 