<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/NCT01712646</url>
  </required_header>
  <id_info>
    <org_study_id>130004</org_study_id>
    <secondary_id>13-M-0004</secondary_id>
    <nct_id>NCT01712646</nct_id>
  </id_info>
  <brief_title>Daily Intranasal Oxytocin for Childhood-Onset Schizophrenia</brief_title>
  <official_title>The Use of Daily, Intranasal Oxytocin for the Treatment of Childhood-Onset Schizophrenia (COS), a Randomized Double-Blind Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Mental Health (NIMH)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      - Oxytocin is a chemical that the brain normally produces. It plays an important part in the&#xD;
      way humans and other animals act in social and emotional situations. Adults with&#xD;
      schizophrenia have been studied to see if oxytocin can reduce some symptoms of schizophrenia,&#xD;
      such as hearing voices, feeling suspicious, and not feeling interested in daily life. These&#xD;
      studies show that oxytocin may help. However, it has not been studied in children who develop&#xD;
      schizophrenia. Researchers want to see if oxytocin, given as a nasal spray, is safe and can&#xD;
      reduce schizophrenia symptoms in children.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      - To see if an oxytocin nasal spray can reduce schizophrenia symptoms in children.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      - Children above 10 years of age who have childhood-onset schizophrenia, and have&#xD;
      schizophrenia symptoms in spite of taking medication.&#xD;
&#xD;
      Design:&#xD;
&#xD;
        -  This study will last 4 weeks. Participants will stay in the hospital for the entire&#xD;
           period of the study. Participants may also have an extra 2 weeks of study medication and&#xD;
           1 week of testing immediately following the initial 4 weeks.&#xD;
&#xD;
        -  Participants will be screened with a physical exam and medical and psychiatric history.&#xD;
           They will provide blood and urine samples, and have imaging studies of the brain. They&#xD;
           will also have tests to look at their social and emotional functioning. These tests will&#xD;
           take 1 week to perform.&#xD;
&#xD;
        -  Participants will have either oxytocin or placebo nasal spray twice daily for 2 weeks.&#xD;
&#xD;
        -  At the end of the 2-week period with nasal spray, there will be 1 week with no nasal&#xD;
           spray. All the tests of week 1 will be repeated.&#xD;
&#xD;
        -  The optional extra 3 weeks (2 weeks with oxytocin and one week for testing) will be&#xD;
           similar to the second, third, and fourth weeks of the study. All participants will have&#xD;
           oxytocin during this period.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background:&#xD;
&#xD;
      Recent studies with intranasal oxytocin administration indicate moderate efficacy in symptom&#xD;
      reduction in adult patients with schizophrenia, and moderate to good response in improving&#xD;
      social cognition in patients with autism. The majority (about 75%) of patients with&#xD;
      childhood-onset schizophrenia (COS) continue to show impairing social and psychotic symptoms&#xD;
      after drug treatment optimization, and almost 30% of children with COS have co-morbid autism&#xD;
      spectrum disorder (ASD). Oxytocin may be a safe and effective adjunctive treatment to improve&#xD;
      social cognition, reduce anxiety, and indirectly reduce psychotic symptoms in&#xD;
      medication-stable COS patients.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To study whether intranasal oxytocin (study medication) would be safe, improve&#xD;
      emotional/social cognition, and reduce symptom severity in clinically stable COS children and&#xD;
      whether the study medication would also result in specific neurocircuitry changes, as&#xD;
      measured by multimodal neuroimaging.&#xD;
&#xD;
      Study Population:&#xD;
&#xD;
      72 patients (36 per group) with COS, ages 10 and above will be recruited. All patients will&#xD;
      be on stable medications for at least one month prior to this study.&#xD;
&#xD;
      Design:&#xD;
&#xD;
      Two-week double-blind, placebo-controlled, parallel design trial of daily intranasal&#xD;
      oxytocin. Subsequent to the study period, a two-week extension of open label study medication&#xD;
      will be offered to all participants, regardless of study group assignment.&#xD;
&#xD;
      Outcome Measures:&#xD;
&#xD;
      Primary Outcome Measures:&#xD;
&#xD;
      To evaluate the safety of intranasal oxytocin in COS patients.&#xD;
&#xD;
      To assess whether intranasal administration of oxytocin will improve both positive and&#xD;
      negative symptoms of schizophrenia compared to placebo, as measured by PANSS, SAPS, SANS, and&#xD;
      BPRS.&#xD;
&#xD;
      To evaluate whether intranasal oxytocin has significant effects on the social and emotional&#xD;
      processing and behavior of children with COS, as measured by the Diagnostic Analysis of&#xD;
      Nonverbal Behavior (DANVA-2), Developmental Neuropsychological Assessment (NEPSY-2)&#xD;
      standardized social perception battery, Brune Theory of Mind Pictures Stories Task, Reading&#xD;
      the Mind in the Eyes Test. Social Responsiveness Scale (SRS).&#xD;
&#xD;
      To measure alterations in neurocircuitry after oxytocin administration, as measured by fMRI,&#xD;
      DTI, and MEG.&#xD;
&#xD;
      To evaluate changes in blood plasma oxytocin levels measured over the course of the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <start_date>October 5, 2012</start_date>
  <primary_completion_date type="Actual">June 20, 2016</primary_completion_date>
  <phase>Phase 1/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>
  </study_design_info>
  <primary_outcome>
    <measure>Blood plasma oxytoxin levels</measure>
  </primary_outcome>
  <primary_outcome>
    <measure>Neuocircuitry alterations in amygdale/cingulated</measure>
  </primary_outcome>
  <primary_outcome>
    <measure>Brain activity alterations during exposure to social stimuli</measure>
  </primary_outcome>
  <primary_outcome>
    <measure>Improved psychosis/anxiety symptoms</measure>
  </primary_outcome>
  <primary_outcome>
    <measure>Improved DANVA-2/NEPSY-2/social interaction scores</measure>
  </primary_outcome>
  <enrollment type="Actual">18</enrollment>
  <condition>Childhood Onset Psychotic Disorders</condition>
  <condition>Schizophrenia</condition>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intranasal Oxytocin</intervention_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
        COS patients (age 10 and above) recruited, enrolled, and diagnosed under the screening&#xD;
        protocol 03-M-0035.&#xD;
&#xD;
        Have been stable on their medications for at least one month prior to enrollment in this&#xD;
        study, with the exception of occasional use of prn (as needed) medication. There are no&#xD;
        contraindications to oxytocin; therefore, all medications are permitted.&#xD;
&#xD;
        Continued problems in social/emotional domains, as evidenced by problems with interpersonal&#xD;
        relationships (e.g., poor ability to relate with others, make friends, have meaningful&#xD;
        social interactions), emotional processing (e.g., difficulty interpreting emotions,&#xD;
        inappropriate emotional responses, significant anxiety around activities of daily living,&#xD;
        lack of empathy), and/or residual symptoms of schizophrenia (e.g., hallucinations,&#xD;
        delusions, flat affect, disorganized thinking/behavior), despite medication.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
        Any major neurological illness (e.g., epilepsy, brain tumors, metabolic disorders).&#xD;
&#xD;
        Is pregnant, plans on becoming pregnant during the study, or is actively breast-feeding.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>10 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Judith L Rapoport, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Institute of Mental Health (NIMH)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center, 9000 Rockville Pike</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Asarnow JR, Ben-Meir S. Children with schizophrenia spectrum and depressive disorders: a comparative study of premorbid adjustment, onset pattern and severity of impairment. J Child Psychol Psychiatry. 1988 Jul;29(4):477-88. doi: 10.1111/j.1469-7610.1988.tb00738.x.</citation>
    <PMID>3215919</PMID>
  </reference>
  <reference>
    <citation>Watkins JM, Asarnow RF, Tanguay PE. Symptom development in childhood onset schizophrenia. J Child Psychol Psychiatry. 1988 Nov;29(6):865-78. doi: 10.1111/j.1469-7610.1988.tb00759.x.</citation>
    <PMID>3235494</PMID>
  </reference>
  <reference>
    <citation>Russell AT, Bott L, Sammons C. The phenomenology of schizophrenia occurring in childhood. J Am Acad Child Adolesc Psychiatry. 1989 May;28(3):399-407. doi: 10.1097/00004583-198905000-00017.</citation>
    <PMID>2738007</PMID>
  </reference>
  <verification_date>June 20, 2016</verification_date>
  <study_first_submitted>October 20, 2012</study_first_submitted>
  <study_first_submitted_qc>October 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 23, 2012</study_first_posted>
  <last_update_submitted>July 6, 2017</last_update_submitted>
  <last_update_submitted_qc>July 6, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 7, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Oxytocin</keyword>
  <keyword>Childhood Onset Schizophrenia</keyword>
  <keyword>Double Blind</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Schizophrenia</mesh_term>
    <mesh_term>Psychotic Disorders</mesh_term>
    <mesh_term>Schizophrenia, Childhood</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Oxytocin</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>January 2, 2019</submitted>
    <returned>January 25, 2019</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01712646
org study id: 130004
secondary id: 13-M-0004
nct id: NCT01712646
lead sponsor: 
Background:

      - Oxytocin is a chemical that the brain normally produces. It plays an important part in the
      way humans and other animals act in social and emotional situations. Adults with
      schizophrenia have been studied to see if oxytocin can reduce some symptoms of schizophrenia,
      such as hearing voices, feeling suspicious, and not feeling interested in daily life. These
      studies show that oxytocin may help. However, it has not been studied in children who develop
      schizophrenia. Researchers want to see if oxytocin, given as a nasal spray, is safe and can
      reduce schizophrenia symptoms in children.

      Objectives:

      - To see if an oxytocin nasal spray can reduce schizophrenia symptoms in children.

      Eligibility:

      - Children above 10 years of age who have childhood-onset schizophrenia, and have
      schizophrenia symptoms in spite of taking medication.

      Design:

        -  This study will last 4 weeks. Participants will stay in the hospital for the entire
           period of the study. Participants may also have an extra 2 weeks of study medication and
           1 week of testing immediately following the initial 4 weeks.

        -  Participants will be screened with a physical exam and medical and psychiatric history.
           They will provide blood and urine samples, and have imaging studies of the brain. They
           will also have tests to look at their social and emotional functioning. These tests will
           take 1 week to perform.

        -  Participants will have either oxytocin or placebo nasal spray twice daily for 2 weeks.

        -  At the end of the 2-week period with nasal spray, there will be 1 week with no nasal
           spray. All the tests of week 1 will be repeated.

        -  The optional extra 3 weeks (2 weeks with oxytocin and one week for testing) will be
           similar to the second, third, and fourth weeks of the study. All participants will have
           oxytocin during this period.
Background:

      Recent studies with intranasal oxytocin administration indicate moderate efficacy in symptom
      reduction in adult patients with schizophrenia, and moderate to good response in improving
      social cognition in patients with autism. The majority (about 75%) of patients with
      childhood-onset schizophrenia (COS) continue to show impairing social and psychotic symptoms
      after drug treatment optimization, and almost 30% of children with COS have co-morbid autism
      spectrum disorder (ASD). Oxytocin may be a safe and effective adjunctive treatment to improve
      social cognition, reduce anxiety, and indirectly reduce psychotic symptoms in
      medication-stable COS patients.

      Objective:

      To study whether intranasal oxytocin (study medication) would be safe, improve
      emotional/social cognition, and reduce symptom severity in clinically stable COS children and
      whether the study medication would also result in specific neurocircuitry changes, as
      measured by multimodal neuroimaging.

      Study Population:

      72 patients (36 per group) with COS, ages 10 and above will be recruited. All patients will
      be on stable medications for at least one month prior to this study.

      Design:

      Two-week double-blind, placebo-controlled, parallel design trial of daily intranasal
      oxytocin. Subsequent to the study period, a two-week extension of open label study medication
      will be offered to all participants, regardless of study group assignment.

      Outcome Measures:

      Primary Outcome Measures:

      To evaluate the safety of intranasal oxytocin in COS patients.

      To assess whether intranasal administration of oxytocin will improve both positive and
      negative symptoms of schizophrenia compared to placebo, as measured by PANSS, SAPS, SANS, and
      BPRS.

      To evaluate whether intranasal oxytocin has significant effects on the social and emotional
      processing and behavior of children with COS, as measured by the Diagnostic Analysis of
      Nonverbal Behavior (DANVA-2), Developmental Neuropsychological Assessment (NEPSY-2)
      standardized social perception battery, Brune Theory of Mind Pictures Stories Task, Reading
      the Mind in the Eyes Test. Social Responsiveness Scale (SRS).

      To measure alterations in neurocircuitry after oxytocin administration, as measured by fMRI,
      DTI, and MEG.

      To evaluate changes in blood plasma oxytocin levels measured over the course of the study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
measure: Blood plasma oxytoxin levels
measure: Neuocircuitry alterations in amygdale/cingulated
measure: Brain activity alterations during exposure to social stimuli
measure: Improved psychosis/anxiety symptoms
measure: Improved DANVA-2/NEPSY-2/social interaction scores
intervention type: Drug
intervention name: Intranasal Oxytocin
criteria: 
gender: All
minimum age: 10 Years
maximum age: 99 Years
healthy volunteers: No
last name: Judith L Rapoport, M.D.
role: Principal Investigator
affiliation: National Institute of Mental Health (NIMH)
facility: 
country: United States
citation: Asarnow JR, Ben-Meir S. Children with schizophrenia spectrum and depressive disorders: a comparative study of premorbid adjustment, onset pattern and severity of impairment. J Child Psychol Psychiatry. 1988 Jul;29(4):477-88. doi: 10.1111/j.1469-7610.1988.tb00738.x.
PMID: 3215919
citation: Watkins JM, Asarnow RF, Tanguay PE. Symptom development in childhood onset schizophrenia. J Child Psychol Psychiatry. 1988 Nov;29(6):865-78. doi: 10.1111/j.1469-7610.1988.tb00759.x.
PMID: 3235494
citation: Russell AT, Bott L, Sammons C. The phenomenology of schizophrenia occurring in childhood. J Am Acad Child Adolesc Psychiatry. 1989 May;28(3):399-407. doi: 10.1097/00004583-198905000-00017.
PMID: 2738007
responsible party type: Sponsor
mesh term: Schizophrenia
mesh term: Psychotic Disorders
mesh term: Schizophrenia, Childhood
mesh term: Oxytocin
submitted: January 2, 2019
returned: January 25, 2019