<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/NCT03032926</url>
  </required_header>
  <id_info>
    <org_study_id>1310014441</org_study_id>
    <nct_id>NCT03032926</nct_id>
  </id_info>
  <brief_title>A Pilot Study of Fear Extinction Learning in Anxious Youth</brief_title>
  <official_title>Enhancing Specificity and Predictability of CBT Outcome for Pediatric Anxiety Disorders: A Pilot Test of a Potential Biomarker for Treatment Response Across Development</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Weill Medical College of Cornell University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Weill Medical College of Cornell University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goal of this proposed study is to identify a potential biobehavioral marker of CBT&#xD;
      outcome in the most common child and adolescent anxiety disorders, including separation&#xD;
      anxiety disorder (SAD), social phobia (SoP), and generalized anxiety disorder (GAD), and to&#xD;
      replicate in a clinical sample the previous finding from animal and non-clinical human&#xD;
      samples that a difference exists in extinction learning across development.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study Sample and Design: The study will utilize an open treatment pilot trial design.&#xD;
      Participants will include 10 individuals, ages 11-18, with a primary anxiety disorder&#xD;
      diagnosis. Participants must not have failed prior trials of CBT. Participants on psychiatric&#xD;
      medication must be on a stable dose for at least 2 months prior to study participation and&#xD;
      remain symptomatic to the level identified for study inclusion (ADIS CSR ≥ 4).&#xD;
&#xD;
      Measures: Independent evaluators will administer a comprehensive assessment at baseline and&#xD;
      post-treatment. The Anxiety Disorder Interview Schedule for Children for DSM-5 (ADIS-C-5)19&#xD;
      will measure the primary outcome of change in clinical severity of anxiety disorder symptoms&#xD;
      across age groups. The Clinical Global Impression Scale (CGI) will assess overall symptom&#xD;
      severity. The PARS and the MASC will provide secondary, dimensional measures of anxiety. In&#xD;
      addition, we will measure treatment adherence and parent engagement as important secondary&#xD;
      variables.&#xD;
&#xD;
      Fear Conditioning &amp; Extinction Paradigm: Subjects will participate in a laboratory test of&#xD;
      extinction training prior to CBT in order to establish extinction learning as a potential&#xD;
      predictive marker of treatment outcome. Subjects will be exposed to two shapes on a computer&#xD;
      screen, one shape (conditioned stimulus (CS+) will be paired with an aversive sound&#xD;
      (unconditioned stimulus) on 38% of the trials, whereas the other shape will never be paired&#xD;
      with aversive sound (CS-)20. A day later, individuals will undergo extinction training in&#xD;
      which the two conditioned stimuli will be repeatedly presented without the unconditioned&#xD;
      stimulus. Extinction will be measured as the difference score of skin conductance response to&#xD;
      the CS+ and CS-.&#xD;
&#xD;
      Exposure Therapy Intervention: investigators will offer participants an 8 session exposure&#xD;
      therapy intervention. Session one will consist of psychoeducation and completion of an&#xD;
      exposure hierarchy. Sessions 2-7 will consist of weekly gradual exposure sessions. Session 8&#xD;
      will include review, relapse prevention and referral to additional treatment if needed.&#xD;
      Assessment measures will be given at the completion of each exposure session to assess&#xD;
      individual differences in symptom change related to exposure therapy. All treatment sessions&#xD;
      will be videotaped to ensure fidelity to treatment manual and modules.&#xD;
&#xD;
      Data analysis plan: Investigators will track the monthly number of participants screened and&#xD;
      enrolled to determine feasibility of a larger trial, as well as session attendance, study&#xD;
      attrition, treatment adherence and patient safety to assess acceptability of the selected&#xD;
      measures and interventions. Though this pilot will not be adequately powered to detect&#xD;
      statistical significance, the investigators will execute a preliminary test of the&#xD;
      association between performance on the extinction learning task and treatment outcome, and&#xD;
      the investigators will assess age group differences in extinction learning and treatment&#xD;
      outcome to determine early proof of concept.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>February 2014</start_date>
  <completion_date type="Actual">July 2016</completion_date>
  <primary_completion_date type="Actual">October 2015</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>ADIS Evaluation</measure>
    <time_frame>1 year</time_frame>
    <description>Anxiety Disorders Interview Schedule for DSM-5-Adult Version</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">9</enrollment>
  <condition>Anxiety Disorder of Childhood</condition>
  <arm_group>
    <arm_group_label>Open Trial</arm_group_label>
    <description>N/A - Open Trial</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Open Trial</intervention_name>
    <description>Behavioral Intervention</description>
    <arm_group_label>Open Trial</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Youth with anxiety disorders ages 7-25&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ages 7-25 years inclusively (i.e., must be at least 7 years) at the point of consent&#xD;
&#xD;
          -  Primary DSM 5 diagnosis of SepAD, SocAD, OCD, specific phobia, or panic disorder on&#xD;
             the ADIS-IV-C/P&#xD;
&#xD;
          -  Anxiety severity of moderate or greater (CGI-S &gt;3 and functional impairment (CGAS&#xD;
             score 60)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Estimated child Full Scale IQ &lt; 80, as measured by the vocabulary and block design&#xD;
             subtests of the WISC-III) (Gate B). If a potential subject has a verified IQ score in&#xD;
             the three years prior to enrollment as measured by the WISC-III, IIIR, K-ABC, or&#xD;
             Stanford-Binet no IQ assessment is required.&#xD;
&#xD;
          -  Child meets criteria for current primary or co-primary major depressive disorder,&#xD;
             conduct disorder or substance abuse&#xD;
&#xD;
          -  Child meets criteria for Major Depressive Disorder at greater severity than anxiety&#xD;
             disorder (Gate B)&#xD;
&#xD;
          -  Subjects with the following lifetime psychiatric disorders will be excluded: bipolar&#xD;
             disorder, PDD (Asperger's, autism), MDD with psychosis, schizophrenia, and&#xD;
             schizoaffective disorder&#xD;
&#xD;
          -  Current use of psychotropic medication or clinical indication for use of psychotropic&#xD;
             medication (except for youth entering on a stable psychostimulant regimen for ADHD)&#xD;
&#xD;
          -  Recent treatment with psychotropic medication within 6 weeks of study entry for&#xD;
             fluoxetine, within 2 weeks for other SSRIs, and within 4 weeks for neuroleptics (Gates&#xD;
             A, B).&#xD;
&#xD;
          -  Child has failed an adequate trial of CBT for anxiety within the previous 2 years (at&#xD;
             least 10 treatment sessions over a period of less than 1 year conducted by a licensed&#xD;
             provider of CBT)&#xD;
&#xD;
          -  Child has a major neurological disorder, a major medical illness or hearing impairment&#xD;
             that requires a prohibited episodic or chronic systemic medication or that would&#xD;
             interfere&#xD;
&#xD;
          -  Child is pregnant as indicated by history or a positive pregnancy test at Gate B.&#xD;
             Sexually active girls must agree to use an effective form of birth control, either&#xD;
             hormonal (BCP, Depo-Provera or Norplant), spermicide (foam or vaginal suppository) or&#xD;
             a barrier method (condoms, diaphragm, cervical cap) or a combination of&#xD;
             barrier/spermicide contraception in order to participate in the study.&#xD;
&#xD;
          -  Child poses a significant risk for dangerousness to self or to others&#xD;
&#xD;
          -  Child or parent is non-English speaking (unable to complete measures, IE ratings or&#xD;
             treatment without the assistance of a translator) NYSPI and UCLA may recruit Spanish&#xD;
             speaking subjects.&#xD;
&#xD;
          -  Child is a victim of ongoing or previously undisclosed child abuse requiring new&#xD;
             department of social service report or ongoing department of social service&#xD;
             supervision&#xD;
&#xD;
          -  Child, for any reason, has missed more than 50% of school days in the 2 months&#xD;
             preceding randomization. Home schooling does not require exclusion from the study&#xD;
             under this exclusion criterion. Ambiguous cases are referred to Caseness Panel to&#xD;
             avoid truncating the severity range differently across sites&#xD;
&#xD;
          -  Child has a history of seizures&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>7 Years</minimum_age>
    <maximum_age>25 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Shannon Bennett, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Weill Medical College of Cornell University</affiliation>
  </overall_official>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>January 23, 2017</study_first_submitted>
  <study_first_submitted_qc>January 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <last_update_submitted>April 15, 2019</last_update_submitted>
  <last_update_submitted_qc>April 15, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 17, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Anxiety</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anxiety Disorders</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03032926
org study id: 1310014441
nct id: NCT03032926
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The goal of this proposed study is to identify a potential biobehavioral marker of CBT
      outcome in the most common child and adolescent anxiety disorders, including separation
      anxiety disorder (SAD), social phobia (SoP), and generalized anxiety disorder (GAD), and to
      replicate in a clinical sample the previous finding from animal and non-clinical human
      samples that a difference exists in extinction learning across development.
Study Sample and Design: The study will utilize an open treatment pilot trial design.
      Participants will include 10 individuals, ages 11-18, with a primary anxiety disorder
      diagnosis. Participants must not have failed prior trials of CBT. Participants on psychiatric
      medication must be on a stable dose for at least 2 months prior to study participation and
      remain symptomatic to the level identified for study inclusion (ADIS CSR ≥ 4).

      Measures: Independent evaluators will administer a comprehensive assessment at baseline and
      post-treatment. The Anxiety Disorder Interview Schedule for Children for DSM-5 (ADIS-C-5)19
      will measure the primary outcome of change in clinical severity of anxiety disorder symptoms
      across age groups. The Clinical Global Impression Scale (CGI) will assess overall symptom
      severity. The PARS and the MASC will provide secondary, dimensional measures of anxiety. In
      addition, we will measure treatment adherence and parent engagement as important secondary
      variables.

      Fear Conditioning & Extinction Paradigm: Subjects will participate in a laboratory test of
      extinction training prior to CBT in order to establish extinction learning as a potential
      predictive marker of treatment outcome. Subjects will be exposed to two shapes on a computer
      screen, one shape (conditioned stimulus (CS+) will be paired with an aversive sound
      (unconditioned stimulus) on 38% of the trials, whereas the other shape will never be paired
      with aversive sound (CS-)20. A day later, individuals will undergo extinction training in
      which the two conditioned stimuli will be repeatedly presented without the unconditioned
      stimulus. Extinction will be measured as the difference score of skin conductance response to
      the CS+ and CS-.

      Exposure Therapy Intervention: investigators will offer participants an 8 session exposure
      therapy intervention. Session one will consist of psychoeducation and completion of an
      exposure hierarchy. Sessions 2-7 will consist of weekly gradual exposure sessions. Session 8
      will include review, relapse prevention and referral to additional treatment if needed.
      Assessment measures will be given at the completion of each exposure session to assess
      individual differences in symptom change related to exposure therapy. All treatment sessions
      will be videotaped to ensure fidelity to treatment manual and modules.

      Data analysis plan: Investigators will track the monthly number of participants screened and
      enrolled to determine feasibility of a larger trial, as well as session attendance, study
      attrition, treatment adherence and patient safety to assess acceptability of the selected
      measures and interventions. Though this pilot will not be adequately powered to detect
      statistical significance, the investigators will execute a preliminary test of the
      association between performance on the extinction learning task and treatment outcome, and
      the investigators will assess age group differences in extinction learning and treatment
      outcome to determine early proof of concept.
observational model: Case-Only
time perspective: Prospective
measure: ADIS Evaluation
time frame: 1 year
description: Anxiety Disorders Interview Schedule for DSM-5-Adult Version
arm group label: Open Trial
description: N/A - Open Trial
intervention type: Behavioral
intervention name: Open Trial
description: Behavioral Intervention
arm group label: Open Trial
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 7 Years
maximum age: 25 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Shannon Bennett, PhD
role: Principal Investigator
affiliation: Weill Medical College of Cornell University
responsible party type: Sponsor
mesh term: Anxiety Disorders
sharing ipd: No