<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/NCT02189213</url>
  </required_header>
  <id_info>
    <org_study_id>6884</org_study_id>
    <nct_id>NCT02189213</nct_id>
  </id_info>
  <brief_title>Treatment of Pediatric Anxiety Disorders by Predicting Treatment Response Through Biocellular Markers and Sleep</brief_title>
  <official_title>Treatment of Pediatric Anxiety Disorders by Predicting Treatment Response Through Biocellular Markers and Sleep</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>New York State Psychiatric Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Columbia University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>New York State Psychiatric Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      1 out of 8 children, adolescents, and young adults suffer from an anxiety disorder. Studies&#xD;
      over the past decade show that selective serotonin-reuptake inhibitors (SSRIs), a class of&#xD;
      medication that treats anxiety in adults, also works well in young adults, children, and&#xD;
      adolescents with anxiety disorders, but only for about 50%. 50% will have undergone treatment&#xD;
      for several months before it will be established that the medication is not working to treat&#xD;
      the anxiety. The purpose of this study is to find a test that will predict treatment outcome&#xD;
      from the beginning based on behavioral and biological measures.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Current evidence based psychiatric treatment for child, adolescent, and young adult anxiety&#xD;
      disorders involves a trial and error process. Pediatric psychiatrists start with the first&#xD;
      line treatments (i.e. SSRI or psychotherapy), which requires from 4-8 weeks to work. There is&#xD;
      a long interval between treatment initiation and response with only 50 to 60% likelihood that&#xD;
      the treatment chosen will succeed in reducing anxiety symptoms. The science that will enable&#xD;
      us to predict who will respond to medication treatment does not exist. Studies have&#xD;
      demonstrated a correlation between cellular markers in white blood cells and psychiatric&#xD;
      disorders suggesting that certain genes may also change their expression in peripheral cells&#xD;
      in response to treatment of psychiatric disorders. Several studies report a significant&#xD;
      decrease in expression of key genes that are involved in the pathophysiology of anxiety and&#xD;
      depression in the brain, such as BDNF, CREB and HDAC5 levels in leukocytes of people with&#xD;
      mood and anxiety disorders. The levels of BDNF, HDAC5 and CREB in white blood cells then&#xD;
      respond to treatment and match that of controls after treatment with SSRIs. The increased&#xD;
      accessibility to sequencing technology allows us to survey many more potential biomarkers&#xD;
      than what was possible just several years ago. This may enable us to formulate a test that&#xD;
      will predict, based on biocellular markers, treatment outcome in anxiety disorders for&#xD;
      children, adolescents, and young adults before the onset of treatment. By finding molecular&#xD;
      markers that can predict treatment success from the onset, the investigators can improve&#xD;
      treatment outcomes considerably compared to current standard treatment practices. This kind&#xD;
      of personalized medicine is the future of psychiatry.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Insufficient funding&#xD;
  </why_stopped>
  <start_date type="Actual">July 2014</start_date>
  <completion_date type="Actual">December 2019</completion_date>
  <primary_completion_date type="Actual">December 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical Global Impression-Improvement (CGI-I) Score</measure>
    <time_frame>Final visit, at 12 weeks of treatment</time_frame>
    <description>The CGI-I score at the final visit will determine treatment response.&#xD;
The CGI-Improvement scale comprises a one-item measures evaluating the following change from the initiation of treatment on a seven-point scale.&#xD;
The following one query is rated on a seven-point scale: &quot;Compared to the patient's condition at admission to the project [prior to medication initiation], this patient's condition is: 1=very much improved since the initiation of treatment; 2=much improved; 3=minimally improved; 4=no change from baseline (the initiation of treatment); 5=minimally worse; 6= much worse; 7=very much worse since the initiation of treatment.&#xD;
CGI-I scale of 1-2 is considered response to treatment. Anything below that is considered non-response to sertraline treatment.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Generalized Anxiety Disorder</condition>
  <condition>Separation Anxiety Disorder</condition>
  <condition>Social Phobia</condition>
  <arm_group>
    <arm_group_label>Sertraline</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Sertraline will be administered PO to treat anxiety disorders in children and adolescents. he following dosing schedules will be used: Sertraline will be titrated from 25mg once a day orally up to 200mg once a day orally, for 12 weeks. The titration will stop at the dose in which the participant shows a full response to the medication or experiences side effects that will inhibit titration.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>There will be no intervention in this arm.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sertraline</intervention_name>
    <description>Sertraline will be administered to treat anxiety disorders in children and adolescents.</description>
    <arm_group_label>Sertraline</arm_group_label>
    <other_name>Zoloft</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Participants aged 8-25 years inclusive at the time of the consent/assent, either&#xD;
             outpatient or inpatient if hospitalization is required for one of the following&#xD;
             reasons:&#xD;
&#xD;
               -  It is presently unsafe for subject to stay at home because he/she may run away&#xD;
&#xD;
               -  Subject needs closer monitoring while being started on medications&#xD;
&#xD;
               -  Subject needs a level of care that is greater than once a week outpatient&#xD;
                  treatment and is willing to participate in the study.&#xD;
&#xD;
          2. Participant's parent or legally authorized representative (LAR) must provide signature&#xD;
             of informed consent, and there must be documentation of assent by the participant.&#xD;
&#xD;
          3. Participant meets Diagnostic and Statistical Manual of Mental Disorders Fourth Edition&#xD;
             (DSM-IV) or Fifth Edition (DSM-V) criteria for a clinically impairing anxiety disorder&#xD;
             based on detailed psychiatric evaluation at screening including completion of the&#xD;
             Anxiety Disorders Interview Schedule for DSM-IV or DSM-V Child Version (ADIS-C) and a&#xD;
             Children's Global Assessment Scale (CGAS) score less than 65.&#xD;
&#xD;
          4. Participants who are female of child-bearing potential (defined as ≥9 years of age or&#xD;
             if &lt;9 years of age are post-menarchal) must have a negative urine pregnancy test at&#xD;
             the Baseline Visit. Females of child-bearing potential must abstain from sexual&#xD;
             activity that could result in pregnancy or agree to use acceptable methods of&#xD;
             contraception. Condoms should be used with the following acceptable contraceptives:&#xD;
&#xD;
               -  Intrauterine devices,&#xD;
&#xD;
               -  Hormonal contraceptives (oral, depot, patch, injectable, or vaginal ring).&#xD;
&#xD;
               -  Other acceptable contraceptive methods are double barrier methods (e.g., condoms&#xD;
                  and diaphragms with spermicidal gel or foam).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Participant has a current co-morbid psychiatric diagnosis of bipolar disorder,&#xD;
             psychosis, a pervasive developmental disorder other than Asperger's Syndrome, an&#xD;
             eating disorder, substance abuse disorder, or a sleep disorder of narcolepsy and/or&#xD;
             sleep apnea.&#xD;
&#xD;
          2. Participant has any condition or illness which, in the opinion of the study doctor,&#xD;
             represents as an inappropriate risk to the participant and/or could confound the&#xD;
             interpretation of the study.&#xD;
&#xD;
          3. Participant has received any evidence-based psychosocial intervention in the past 6&#xD;
             weeks i.e. Individual Cognitive Behavioral Therapy, Group Cognitive Behavioral&#xD;
             Therapy, or Social Effectiveness Training.&#xD;
&#xD;
          4. Participant is unwilling or unable to provide blood, urine, and/or saliva samples at&#xD;
             designated visits.&#xD;
&#xD;
          5. Participant is female and is pregnant or is currently lactating.&#xD;
&#xD;
          6. Participant is currently considered at risk for suicide in the opinion of the study&#xD;
             doctor, has made a suicide attempt within the past 6 months, or is currently reporting&#xD;
             active suicidal ideation. Participants with intermittent passive suicidal ideation are&#xD;
             not necessarily excluded based on the assessment of the study doctor. Control&#xD;
             participants with any suicidal ideation will not be eligible for the study.&#xD;
&#xD;
          7. Participant has had a substance use disorder within the past 6 months.&#xD;
&#xD;
          8. Participant has a clinically important abnormality on drug and alcohol screen.&#xD;
&#xD;
          9. Participant has started or changed the dosage of medication (including herbal&#xD;
             supplements) that has anxiolytic, anxiogenic, or central nervous system (CNS) effects&#xD;
             within the past 3 months.&#xD;
&#xD;
         10. Participant has a known or suspected allergy, hypersensitivity, or clinically&#xD;
             significant intolerance to any components found in the study drug.&#xD;
&#xD;
         11. Participant has had several failed attempts with SSRI treatment.&#xD;
&#xD;
         12. Participant has an acute illness and/or is taking short term medication at the time of&#xD;
             initiation of the study.&#xD;
&#xD;
         13. Participant failed screening or was previously enrolled in this study&#xD;
&#xD;
         14. Participant is unable to read.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>8 Years</minimum_age>
    <maximum_age>25 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Amir Levine</last_name>
    <role>Principal Investigator</role>
    <affiliation>New York State Psychiatric Institue</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>NYSPI</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>July 7, 2014</study_first_submitted>
  <study_first_submitted_qc>July 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 14, 2014</study_first_posted>
  <results_first_submitted>June 22, 2021</results_first_submitted>
  <results_first_submitted_qc>September 14, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">October 11, 2021</results_first_posted>
  <disposition_first_submitted>February 18, 2021</disposition_first_submitted>
  <disposition_first_submitted_qc>March 9, 2021</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">March 10, 2021</disposition_first_posted>
  <last_update_submitted>September 14, 2021</last_update_submitted>
  <last_update_submitted_qc>September 14, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 11, 2021</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>Amir A. Levine</investigator_full_name>
    <investigator_title>Psychiatrist 2/Associate Professor of Clinical Psychiatry</investigator_title>
  </responsible_party>
  <keyword>anxiety</keyword>
  <keyword>SSRI</keyword>
  <keyword>biomarker</keyword>
  <keyword>sleep</keyword>
  <keyword>children</keyword>
  <keyword>adolescents</keyword>
  <keyword>young adults</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anxiety Disorders</mesh_term>
    <mesh_term>Phobia, Social</mesh_term>
    <mesh_term>Anxiety, Separation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sertraline</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>May 15, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/13/NCT02189213/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>August 30, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/13/NCT02189213/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Sertraline</title>
          <description>Sertraline was administered PO to treat anxiety disorders in children and adolescents. One of the following dosing schedules will be used:&#xD;
Sertraline will be titrated from 25mg once a day orally up to 200mg once a day orally, for 12 weeks, or, the titration was stopped at the dose in which the participant shows a full response to the medication or experiences side effects that will inhibit titration.</description>
        </group>
        <group group_id="P2">
          <title>Healthy Control</title>
          <description>Healthy control will not be treated.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Sertraline</title>
          <description>Sertraline will be administered PO to treat anxiety disorders in children and adolescents. One of the following dosing schedules will be used:&#xD;
Sertraline will be titrated from 25mg once a day orally up to 200mg once a day orally, for 12 weeks, or the titration will stop at the dose in which the participant shows a full response to the medication or experiences side effects that will inhibit titration.</description>
        </group>
        <group group_id="B2">
          <title>Control</title>
          <description>There will be no intervention 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="13"/>
            <count group_id="B2" value="1"/>
            <count group_id="B3" value="14"/>
          </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="12"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </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="8"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="5"/>
                  </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="2"/>
                    <measurement group_id="B2" value="1"/>
                    <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="0"/>
                    <measurement group_id="B3" value="11"/>
                  </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="13"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Clinical Global Impression-Improvement (CGI-I) Score</title>
        <description>The CGI-I score at the final visit will determine treatment response.&#xD;
The CGI-Improvement scale comprises a one-item measures evaluating the following change from the initiation of treatment on a seven-point scale.&#xD;
The following one query is rated on a seven-point scale: &quot;Compared to the patient's condition at admission to the project [prior to medication initiation], this patient's condition is: 1=very much improved since the initiation of treatment; 2=much improved; 3=minimally improved; 4=no change from baseline (the initiation of treatment); 5=minimally worse; 6= much worse; 7=very much worse since the initiation of treatment.&#xD;
CGI-I scale of 1-2 is considered response to treatment. Anything below that is considered non-response to sertraline treatment.</description>
        <time_frame>Final visit, at 12 weeks of treatment</time_frame>
        <population>There were two males and two females in the responder group and two females and one male in the non-responder group.</population>
        <group_list>
          <group group_id="O1">
            <title>Sertraline Responders</title>
            <description>Responders will have either a score of 1 or 2 on the Clinical Global Impressions (CGI) Improvement Scale. The CGI-Improvement scale comprises a one-item measures evaluating the following change from the initiation of treatment on a seven-point scale.&#xD;
The following one query is rated on a seven-point scale: &quot;Compared to the patient's condition at admission to the project [prior to medication initiation], this patient's condition is: 1=very much improved since the initiation of treatment; 2=much improved; 3=minimally improved; 4=no change from baseline (the initiation of treatment); 5=minimally worse; 6= much worse; 7=very much worse since the initiation of treatment.&#xD;
CGI-I scale of 1-2 is considered response to treatment. Anything below that is considered non-response to sertraline treatment.</description>
          </group>
          <group group_id="O2">
            <title>Sertraline Non-Responders</title>
            <description>Non-Responders will have a score of 3 or greater than 3 on the Clinical Global Impressions (CGI) Improvement Scale. The CGI-Improvement scale comprises a one-item measures evaluating the following change from the initiation of treatment on a seven-point scale.&#xD;
The following one query is rated on a seven-point scale: &quot;Compared to the patient's condition at admission to the project [prior to medication initiation], this patient's condition is: 1=very much improved since the initiation of treatment; 2=much improved; 3=minimally improved; 4=no change from baseline (the initiation of treatment); 5=minimally worse; 6= much worse; 7=very much worse since the initiation of treatment.&#xD;
CGI-I scale of 1-2 is considered response to treatment. Anything below that is considered non-response to sertraline treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Global Impression-Improvement (CGI-I) Score</title>
          <description>The CGI-I score at the final visit will determine treatment response.&#xD;
The CGI-Improvement scale comprises a one-item measures evaluating the following change from the initiation of treatment on a seven-point scale.&#xD;
The following one query is rated on a seven-point scale: &quot;Compared to the patient's condition at admission to the project [prior to medication initiation], this patient's condition is: 1=very much improved since the initiation of treatment; 2=much improved; 3=minimally improved; 4=no change from baseline (the initiation of treatment); 5=minimally worse; 6= much worse; 7=very much worse since the initiation of treatment.&#xD;
CGI-I scale of 1-2 is considered response to treatment. Anything below that is considered non-response to sertraline treatment.</description>
          <population>There were two males and two females in the responder group and two females and one male in the non-responder group.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.00" spread="1.40"/>
                    <measurement group_id="O2" value="3.66" spread="2.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>At least 50% of subjects will respond to Sertraline treatment (CGI greater than or equal to 2).</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>The parameters were the CGI-Improvement scale which comprises a one-item measures evaluating the following change from the initiation of treatment on a seven-point scale. The hypothesis is that ~50% of subjects receiving treatment will not respond.</non_inferiority_desc>
            <p_value>=0.0002</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data was collected for 12 weeks during the duration the patients were receiving medications. Only participants who were treated and healthy controls were monitored/assessed for adverse events.</time_frame>
      <desc>We collected adverse events using the Pediatric Adverse Event Rating Scale (PAERS-Clinician)</desc>
      <group_list>
        <group group_id="E1">
          <title>Sertraline</title>
          <description>Sertraline was administered PO to treat anxiety disorders in children and adolescents. One of the following dosing schedules will be used:&#xD;
Sertraline will be titrated from 25mg once a day orally up to 200mg once a day orally, for 12 weeks, or, the titration was stopped at the dose in which the participant shows a full response to the medication or experiences side effects that will inhibit titration.</description>
        </group>
        <group group_id="E2">
          <title>Healthy Control</title>
          <description>Healthy control will not be treated.</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="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <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="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </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>Amir Levine</name_or_title>
      <organization>RFMH</organization>
      <phone>646 481 2566</phone>
      <email>amir.levine@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/NCT02189213
org study id: 6884
nct id: NCT02189213
lead sponsor: 
collaborator: 
has dmc: Yes
1 out of 8 children, adolescents, and young adults suffer from an anxiety disorder. Studies
      over the past decade show that selective serotonin-reuptake inhibitors (SSRIs), a class of
      medication that treats anxiety in adults, also works well in young adults, children, and
      adolescents with anxiety disorders, but only for about 50%. 50% will have undergone treatment
      for several months before it will be established that the medication is not working to treat
      the anxiety. The purpose of this study is to find a test that will predict treatment outcome
      from the beginning based on behavioral and biological measures.
Current evidence based psychiatric treatment for child, adolescent, and young adult anxiety
      disorders involves a trial and error process. Pediatric psychiatrists start with the first
      line treatments (i.e. SSRI or psychotherapy), which requires from 4-8 weeks to work. There is
      a long interval between treatment initiation and response with only 50 to 60% likelihood that
      the treatment chosen will succeed in reducing anxiety symptoms. The science that will enable
      us to predict who will respond to medication treatment does not exist. Studies have
      demonstrated a correlation between cellular markers in white blood cells and psychiatric
      disorders suggesting that certain genes may also change their expression in peripheral cells
      in response to treatment of psychiatric disorders. Several studies report a significant
      decrease in expression of key genes that are involved in the pathophysiology of anxiety and
      depression in the brain, such as BDNF, CREB and HDAC5 levels in leukocytes of people with
      mood and anxiety disorders. The levels of BDNF, HDAC5 and CREB in white blood cells then
      respond to treatment and match that of controls after treatment with SSRIs. The increased
      accessibility to sequencing technology allows us to survey many more potential biomarkers
      than what was possible just several years ago. This may enable us to formulate a test that
      will predict, based on biocellular markers, treatment outcome in anxiety disorders for
      children, adolescents, and young adults before the onset of treatment. By finding molecular
      markers that can predict treatment success from the onset, the investigators can improve
      treatment outcomes considerably compared to current standard treatment practices. This kind
      of personalized medicine is the future of psychiatry.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Clinical Global Impression-Improvement (CGI-I) Score
time frame: Final visit, at 12 weeks of treatment
description: The CGI-I score at the final visit will determine treatment response.
The CGI-Improvement scale comprises a one-item measures evaluating the following change from the initiation of treatment on a seven-point scale.
The following one query is rated on a seven-point scale: "Compared to the patient's condition at admission to the project [prior to medication initiation], this patient's condition is: 1=very much improved since the initiation of treatment; 2=much improved; 3=minimally improved; 4=no change from baseline (the initiation of treatment); 5=minimally worse; 6= much worse; 7=very much worse since the initiation of treatment.
CGI-I scale of 1-2 is considered response to treatment. Anything below that is considered non-response to sertraline treatment.
arm group label: Sertraline
arm group type: Active Comparator
description: Sertraline will be administered PO to treat anxiety disorders in children and adolescents. he following dosing schedules will be used: Sertraline will be titrated from 25mg once a day orally up to 200mg once a day orally, for 12 weeks. The titration will stop at the dose in which the participant shows a full response to the medication or experiences side effects that will inhibit titration.
arm group label: Control
arm group type: No Intervention
description: There will be no intervention in this arm.
intervention type: Drug
intervention name: Sertraline
description: Sertraline will be administered to treat anxiety disorders in children and adolescents.
arm group label: Sertraline
other name: Zoloft
criteria: 
gender: All
minimum age: 8 Years
maximum age: 25 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Amir Levine
role: Principal Investigator
affiliation: New York State Psychiatric Institue
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: New York State Psychiatric Institute
investigator full name: Amir A. Levine
investigator title: Psychiatrist 2/Associate Professor of Clinical Psychiatry
mesh term: Anxiety Disorders
mesh term: Phobia, Social
mesh term: Anxiety, Separation
mesh term: Sertraline
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 