<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/NCT03790696</url>
  </required_header>
  <id_info>
    <org_study_id>201702012</org_study_id>
    <nct_id>NCT03790696</nct_id>
  </id_info>
  <brief_title>Novel Anxiety Treatment</brief_title>
  <official_title>A Novel Mechanism-Based Treatment for Pediatric Anxiety Disorders</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Washington University School of Medicine</source>
  <oversight_info>
    <has_dmc>No</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 first aim of this study, as mentioned in the attached NIH grant, is to test the&#xD;
      feasibility and acceptability of a novel computer-based cognitive training program that is&#xD;
      designed to rehabilitate the brain's ventral attention network (VAN), a brain system&#xD;
      associated with anxiety disorders.&#xD;
&#xD;
      Once feasibility and acceptability is determined the investigators will begin aim 2 where the&#xD;
      investigators will test the efficacy of this novel treatment, which could reduce the symptoms&#xD;
      of anxiety disorders in children (and adults) by training them to actively ignore stimuli in&#xD;
      turn reducing the activity of the VAN. To test this potential treatment the investigators&#xD;
      will recruit 60 children with anxiety disorders and 10 healthy children to compare an active&#xD;
      version of a computer training program to a sham version of training. The investigators will&#xD;
      also measure VAN reactivity before and after treatment using functional magnetic resonance&#xD;
      imaging (fMRI). The rationale of this research is that it could lead to a novel, safe,&#xD;
      mechanism-based treatment for a major public health problem.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Children will be recruited through local schools, pediatricians' offices, and through Dr.&#xD;
      Sylvester's child anxiety clinic by asking staff to present Institutional Review Board (IRB)&#xD;
      approved recruitment materials to potentially interested families. The investigators will&#xD;
      also recruit with advertisements and placement of approved flyers, paragraphs and materials&#xD;
      throughout the greater Washington University community as well as throughout the St. Louis&#xD;
      community.&#xD;
&#xD;
      The research assistant will make 'screening materials' available to recruitment sites&#xD;
      including schools and pediatricians' offices. Staff at these recruitment sites will identify&#xD;
      potential participants and distribute materials accordingly. Staff will only provide&#xD;
      recruitment materials and will not answer questions regarding the study -- all questions will&#xD;
      be answered by study staff. Screening materials will include a consent script, the contact&#xD;
      information sheet, the SCARED, and the MFQ.&#xD;
&#xD;
      A member of the research team will review screening materials and contact potential&#xD;
      participants by phone on the basis of meeting inclusion criteria. This member of the research&#xD;
      team will provide parent participants with information about the study and required elements&#xD;
      of consent over the telephone (see attached &quot;Initial Phone Screen&quot;) prior to obtaining the&#xD;
      parent's verbal consent to participate in the screening elements of the study (Initial Phone&#xD;
      Screen as well as SCARED/MFQ).&#xD;
&#xD;
      If a parent and child meet eligibility criteria for enrollment in the study based on their&#xD;
      Initial Phone Screen, and parents indicate they wish to continue with the study, the research&#xD;
      team will arrange an in-person assessment. On the day of the in-person assessment, a research&#xD;
      assistant will provide ample time for the parents to read/review the consent form and will&#xD;
      answer any questions the parent may have prior to signing. Research team members will remind&#xD;
      participants that their participation is completely voluntary and they can choose to withdraw&#xD;
      at any time.&#xD;
&#xD;
      After the in-person assessment, the participant may be asked to return for another visit to&#xD;
      complete functional magnetic resonance imaging. This additional visit will be optional and&#xD;
      not a requirement of participation in the overall study. The subject can choose not to&#xD;
      participate in this phase of the study and may withdraw at any time. If the subject is&#xD;
      interested, the investigators will obtain a separate document of informed consent for the&#xD;
      imaging phase. As in the original informed consent document, immediately after the in-person&#xD;
      assessment, a research assistant will provide ample time for the parents to read/review the&#xD;
      imaging consent form and will answer any questions the parent may have prior to signing.&#xD;
&#xD;
      The research assistant may also ask the participants at the end of the in-person assessment&#xD;
      whether the investigators could call them in the future to participate in the imaging phase&#xD;
      of the study. If the participant agrees, the team will call the participant within the next 3&#xD;
      months to set up an appointment. In this case, the informed consent for imaging would be&#xD;
      obtained at the beginning of the imaging visit with all of the above procedures applying.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 2, 2017</start_date>
  <completion_date type="Actual">March 31, 2020</completion_date>
  <primary_completion_date type="Actual">March 31, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Factorial Assignment</intervention_model>
    <intervention_model_description>This study is a randomized control trial.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Subjects will be randomized to active vs. sham treatment on a 50/50 basis. The participants and the staff performing the pre- and post- treatment psychiatric interviews will remain blinded throughout the study. Study staff administering the treatment will be aware of the active vs. sham status of the participant, in order to deliver and monitor the appropriate cognitive training program.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in symptoms of anxiety based on Screen for Anxiety and Related Disorders (SCARED)</measure>
    <time_frame>Children/Caregivers will complete the SCARED measure at their baseline appointment before beginning treatment, at treatment session 2,4,6,8, as well as at their final appointment after 4 weeks of completing the training.</time_frame>
    <description>The primary outcome will be reduction in symptoms of anxiety as measured by the SCARED in study Phase 2. Total SCARED scores at sessions 2, 4, 6, and 8 will be subtracted from the baseline SCARED score, yielding a delta SCARED score for each visit. These data will be analyzed with a mixed random effects repeated-measures model. In this model, time, treatment (active versus sham), and time x treatment interaction are fixed effects; baseline SCARED scores and subject within treatment are random effects; and delta SCARED scores are the dependent variable. Our hypothesis predicts a significant time x treatment interaction, with a greater decrease in anxiety from pre-training to their last measurement relative to the sham group. A total score of ≥ 25 may indicate the presence of an Anxiety Disorder. Scores higher than 30 are more specific. The minimum score is a 0 and maximum score is 82.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in symptoms of anxiety based on Pediatric Anxiety Rating Scale (PARS).</measure>
    <time_frame>The PARS measure will be collected at the baseline appointment before subjects begin the cognitive training as well as after completing 8 cognitive training sessions in four weeks.</time_frame>
    <description>Secondary outcomes will include symptoms of anxiety on the PARS and diagnostic status. The investigators will test whether active versus sham training significantly reduces symptoms in children with anxiety disorders. The primary outcome will be reduction in symptoms of anxiety as measured by the PARS. The investigators will perform a 2 x 2 ANOVA with treatment arm (active versus sham) and time (pre-training versus last measurement) as effects of interest.&#xD;
The PARS is a clinician-administered measure of pediatric anxiety that incorporates both parent and child report.The total score for the PARS is total of the 7 severity items. The total score ranges from 0 to 35.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Cognitive Training</condition>
  <condition>Anxiety Disorders</condition>
  <arm_group>
    <arm_group_label>Active Cognitive Training</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will complete 30-45 minute cognitive training program twice a week for four weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham Cognitive Training</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Participants will complete 30-45 minute cognitive training program twice a week for four weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Cognitive Training Program</intervention_name>
    <description>The cognitive training program has been designed by Dr. Sylvester. It is a simple computer game looking at some shapes and faces on a computer screen and pressing a button when a target shape appears.&#xD;
This is the first study to use this exact computer training regimen for testing in its ability to reduce symptoms of anxiety in children with anxiety disorders. Each session of the computer game takes approximately 45-60 minutes and subjects complete 8 total sessions over one month. The computer game involves paying attention to parts of the screen while distracting square boxes appear at other locations. A target &quot;X&quot; appears at the location that participants are paying attention to and the subjects press a button when it appears.</description>
    <arm_group_label>Active Cognitive Training</arm_group_label>
    <arm_group_label>Sham Cognitive Training</arm_group_label>
    <other_name>novel computer-based cognitive training program</other_name>
    <other_name>computer-delivered cognitive training program</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ages of 8-12&#xD;
&#xD;
          -  have a current diagnosis of separation anxiety disorder, generalized anxiety disorder,&#xD;
             and/or social phobia.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  prior diagnoses of attention deficit hyperactivity disorder (ADHD)&#xD;
&#xD;
          -  autism spectrum disorder&#xD;
&#xD;
          -  intellectual disability (IQ&lt;70)&#xD;
&#xD;
          -  a significant medical problem&#xD;
&#xD;
          -  current use of psychotropic medication other than selective serotonin reuptake&#xD;
             inhibitor (SSRI) (children who are currently taking an SSRI and are still experiencing&#xD;
             symptoms of anxiety will not be excluded).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>8 Years</minimum_age>
    <maximum_age>12 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Washinton University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>December 18, 2018</study_first_submitted>
  <study_first_submitted_qc>December 26, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">January 2, 2019</study_first_posted>
  <last_update_submitted>July 19, 2021</last_update_submitted>
  <last_update_submitted_qc>July 19, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 20, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anxiety Disorders</mesh_term>
  </condition_browse>
  <pending_results>
    <submitted>November 16, 2022</submitted>
    <returned>December 15, 2022</returned>
    <submitted>January 29, 2023</submitted>
    <returned>February 27, 2023</returned>
    <submitted>March 3, 2023</submitted>
    <returned>March 31, 2023</returned>
    <submitted>May 19, 2023</submitted>
    <returned>June 9, 2023</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/NCT03790696
org study id: 201702012
nct id: NCT03790696
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The first aim of this study, as mentioned in the attached NIH grant, is to test the
      feasibility and acceptability of a novel computer-based cognitive training program that is
      designed to rehabilitate the brain's ventral attention network (VAN), a brain system
      associated with anxiety disorders.

      Once feasibility and acceptability is determined the investigators will begin aim 2 where the
      investigators will test the efficacy of this novel treatment, which could reduce the symptoms
      of anxiety disorders in children (and adults) by training them to actively ignore stimuli in
      turn reducing the activity of the VAN. To test this potential treatment the investigators
      will recruit 60 children with anxiety disorders and 10 healthy children to compare an active
      version of a computer training program to a sham version of training. The investigators will
      also measure VAN reactivity before and after treatment using functional magnetic resonance
      imaging (fMRI). The rationale of this research is that it could lead to a novel, safe,
      mechanism-based treatment for a major public health problem.
Children will be recruited through local schools, pediatricians' offices, and through Dr.
      Sylvester's child anxiety clinic by asking staff to present Institutional Review Board (IRB)
      approved recruitment materials to potentially interested families. The investigators will
      also recruit with advertisements and placement of approved flyers, paragraphs and materials
      throughout the greater Washington University community as well as throughout the St. Louis
      community.

      The research assistant will make 'screening materials' available to recruitment sites
      including schools and pediatricians' offices. Staff at these recruitment sites will identify
      potential participants and distribute materials accordingly. Staff will only provide
      recruitment materials and will not answer questions regarding the study -- all questions will
      be answered by study staff. Screening materials will include a consent script, the contact
      information sheet, the SCARED, and the MFQ.

      A member of the research team will review screening materials and contact potential
      participants by phone on the basis of meeting inclusion criteria. This member of the research
      team will provide parent participants with information about the study and required elements
      of consent over the telephone (see attached "Initial Phone Screen") prior to obtaining the
      parent's verbal consent to participate in the screening elements of the study (Initial Phone
      Screen as well as SCARED/MFQ).

      If a parent and child meet eligibility criteria for enrollment in the study based on their
      Initial Phone Screen, and parents indicate they wish to continue with the study, the research
      team will arrange an in-person assessment. On the day of the in-person assessment, a research
      assistant will provide ample time for the parents to read/review the consent form and will
      answer any questions the parent may have prior to signing. Research team members will remind
      participants that their participation is completely voluntary and they can choose to withdraw
      at any time.

      After the in-person assessment, the participant may be asked to return for another visit to
      complete functional magnetic resonance imaging. This additional visit will be optional and
      not a requirement of participation in the overall study. The subject can choose not to
      participate in this phase of the study and may withdraw at any time. If the subject is
      interested, the investigators will obtain a separate document of informed consent for the
      imaging phase. As in the original informed consent document, immediately after the in-person
      assessment, a research assistant will provide ample time for the parents to read/review the
      imaging consent form and will answer any questions the parent may have prior to signing.

      The research assistant may also ask the participants at the end of the in-person assessment
      whether the investigators could call them in the future to participate in the imaging phase
      of the study. If the participant agrees, the team will call the participant within the next 3
      months to set up an appointment. In this case, the informed consent for imaging would be
      obtained at the beginning of the imaging visit with all of the above procedures applying.
allocation: Randomized
intervention model: Factorial Assignment
intervention model description: This study is a randomized control trial.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Subjects will be randomized to active vs. sham treatment on a 50/50 basis. The participants and the staff performing the pre- and post- treatment psychiatric interviews will remain blinded throughout the study. Study staff administering the treatment will be aware of the active vs. sham status of the participant, in order to deliver and monitor the appropriate cognitive training program.
measure: Change in symptoms of anxiety based on Screen for Anxiety and Related Disorders (SCARED)
time frame: Children/Caregivers will complete the SCARED measure at their baseline appointment before beginning treatment, at treatment session 2,4,6,8, as well as at their final appointment after 4 weeks of completing the training.
description: The primary outcome will be reduction in symptoms of anxiety as measured by the SCARED in study Phase 2. Total SCARED scores at sessions 2, 4, 6, and 8 will be subtracted from the baseline SCARED score, yielding a delta SCARED score for each visit. These data will be analyzed with a mixed random effects repeated-measures model. In this model, time, treatment (active versus sham), and time x treatment interaction are fixed effects; baseline SCARED scores and subject within treatment are random effects; and delta SCARED scores are the dependent variable. Our hypothesis predicts a significant time x treatment interaction, with a greater decrease in anxiety from pre-training to their last measurement relative to the sham group. A total score of ≥ 25 may indicate the presence of an Anxiety Disorder. Scores higher than 30 are more specific. The minimum score is a 0 and maximum score is 82.
measure: Change in symptoms of anxiety based on Pediatric Anxiety Rating Scale (PARS).
time frame: The PARS measure will be collected at the baseline appointment before subjects begin the cognitive training as well as after completing 8 cognitive training sessions in four weeks.
description: Secondary outcomes will include symptoms of anxiety on the PARS and diagnostic status. The investigators will test whether active versus sham training significantly reduces symptoms in children with anxiety disorders. The primary outcome will be reduction in symptoms of anxiety as measured by the PARS. The investigators will perform a 2 x 2 ANOVA with treatment arm (active versus sham) and time (pre-training versus last measurement) as effects of interest.
The PARS is a clinician-administered measure of pediatric anxiety that incorporates both parent and child report.The total score for the PARS is total of the 7 severity items. The total score ranges from 0 to 35.
arm group label: Active Cognitive Training
arm group type: Experimental
description: Participants will complete 30-45 minute cognitive training program twice a week for four weeks.
arm group label: Sham Cognitive Training
arm group type: Sham Comparator
description: Participants will complete 30-45 minute cognitive training program twice a week for four weeks.
intervention type: Device
intervention name: Cognitive Training Program
description: The cognitive training program has been designed by Dr. Sylvester. It is a simple computer game looking at some shapes and faces on a computer screen and pressing a button when a target shape appears.
This is the first study to use this exact computer training regimen for testing in its ability to reduce symptoms of anxiety in children with anxiety disorders. Each session of the computer game takes approximately 45-60 minutes and subjects complete 8 total sessions over one month. The computer game involves paying attention to parts of the screen while distracting square boxes appear at other locations. A target "X" appears at the location that participants are paying attention to and the subjects press a button when it appears.
arm group label: Active Cognitive Training
arm group label: Sham Cognitive Training
other name: novel computer-based cognitive training program
other name: computer-delivered cognitive training program
criteria: 
gender: All
minimum age: 8 Years
maximum age: 12 Years
healthy volunteers: No
facility: 
country: United States
responsible party type: Sponsor
mesh term: Anxiety Disorders
submitted: November 16, 2022
returned: December 15, 2022
submitted: January 29, 2023
returned: February 27, 2023
submitted: March 3, 2023
returned: March 31, 2023
submitted: May 19, 2023
returned: June 9, 2023