xml: <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/NCT06007053</url>
    </required_header>
    <id_info>
      <org_study_id>IRB-151001004</org_study_id>
      <nct_id>NCT06007053</nct_id>
    </id_info>
    <brief_title>Retraining and Control Therapy (ReACT) R33 Phase</brief_title>
    <acronym>ReACT</acronym>
    <official_title>Retraining and Control Therapy (ReACT): Sense of Control and Catastrophic Symptom Expectations as Targets of a Cognitive Behavioral Treatment for Pediatric Psychogenic Non-epileptic Seizures (PNES) - R33 Phase</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Alabama at Birmingham</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>National Institute of Mental Health (NIMH)</agency>
        <agency_class>NIH</agency_class>
      </collaborator>
    </sponsors>
    <source>University of Alabama at Birmingham</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 purpose of this study is to assess sense of control and catastrophic symptom expectations&#xD;
        as targets for Retraining and Control Therapy (ReACT- an intervention focused on changing&#xD;
        behaviors and thoughts) for treatment of pediatric psychogenic non-epileptic seizures (PNES,&#xD;
        episodes resembling epileptic seizures but with no correlated epileptiform activity).&#xD;
        11-18-year-olds diagnosed with PNES will engage in twelve sessions of either ReACT or&#xD;
        supportive therapy. Sense of control over actions will be measured by the magic and&#xD;
        turbulence task, a well-validated measure of sense of control. Participants will complete the&#xD;
        cold pressor test (CPT) in which participants hold their hand in cool water for as long as&#xD;
        possible up to 3 minutes. Catastrophic symptom expectations in response to the CPT will be&#xD;
        measured by Pain Catastrophizing Scale for Children (PCS-C), pain tolerance (time with hand&#xD;
        in water) and cortisol response. Target assessments occur 7 days before treatment, 7 days&#xD;
        after 12th treatment session, and 6 months after the 12th treatment session. PNES frequency&#xD;
        will be measured from 30 days before to 6 months after treatment.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Participants with PNES and their parent come to our laboratory for a baseline visit and 2&#xD;
        follow-up visits. After the baseline visit, participants are randomized to 12 sessions of&#xD;
        either Retraining and Control Therapy (ReACT) or supportive therapy. The first therapy&#xD;
        session is in-person, and the following 11 sessions are completed via telehealth.&#xD;
  &#xD;
        During the baseline visit, participants and their parent complete several questionnaires&#xD;
        assessing demographics, mood and suicidality, relationships with friends and family, as well&#xD;
        as past and current PNES symptoms. They also complete the childhood trauma questionnaire. The&#xD;
        treatment targets (sense of control and catastrophic symptom expectations) are measured by&#xD;
        the magic and turbulence computer task and pain tolerance, PCS-C and cortisol response to the&#xD;
        CPT, respectively. PNES diaries are completed to assess PNES frequency over the previous 30&#xD;
        days. The baseline lab visit lasts about 2.5 hours. Saliva is collected over 3 time points&#xD;
        before and after the CPT to measure cortisol response to the CPT. Participants also collect 2&#xD;
        saliva samples 24 hours later to serve as a baseline outside of the laboratory setting.&#xD;
        Participants will also be given a Respironics Actiwatch Spectrum Pro to track sleep and PNES&#xD;
        episode severity and frequency for the 1 week between the baseline visit and first therapy&#xD;
        session.&#xD;
  &#xD;
        After the baseline visit, participants are scheduled to return in one week for their first of&#xD;
        12 intervention sessions of either ReACT or supportive therapy. This first session lasts a&#xD;
        maximum of two hours, and the following 11 sessions are scheduled weekly and last one hour.&#xD;
        The following 11 sessions are conducted as telehealth visits via HIPAA-compliant Zoom. Before&#xD;
        beginning the first ReACT session, participants will complete the Flanker Inhibitory Control&#xD;
        and Attention, List Sorting Working Memory, Pattern Comparison Processing Speed, Dimensional&#xD;
        Change Card Sort, and Picture Sequence Memory subtests. Participants will be mailed another&#xD;
        Respironics Actiwatch Spectrum Pro before the 11th therapy session to track sleep and PNES&#xD;
        episode severity and frequency for the 2 weeks between the 11th therapy session and the lab&#xD;
        visit one week after the 12th treatment session.&#xD;
  &#xD;
        Follow-up at 7 days after treatment and 6 months after treatment also is conducted to perform&#xD;
        tasks and complete follow-up assessment of the targets (sense of control and catastrophic&#xD;
        symptom expectations), PNES frequency, and questionnaires. Each of these sessions last 2&#xD;
        hours. Participants will complete the Flanker Inhibitory Control and Attention, List Sorting&#xD;
        Working Memory, Pattern Comparison Processing Speed, Dimensional Change Card Sort, and&#xD;
        Picture Sequence Memory subtests at the lab visit at each of these visits. A Zoom visit will&#xD;
        be completed at 12 months after treatment to assess long-term PNES outcomes and questionnaire&#xD;
        data. This appointment will last 1 hour. PNES frequency will be measured from 30 days before&#xD;
        treatment to 12 months after treatment through PNES diaries completed by the parent and the&#xD;
        participant.&#xD;
  &#xD;
        Participants will be offered the treatment to which they were not randomized after the&#xD;
        6-month follow-up when the study is completed.&#xD;
  &#xD;
        After treatment, booster therapy sessions will be offered as needed.&#xD;
  &#xD;
        Healthy controls will be recruited. Healthy controls and their parent come for a baseline&#xD;
        laboratory visit and a follow up visit 13 weeks after the baseline visit. The baseline and&#xD;
        follow-up appointments for healthy controls will be identical to the visits for children with&#xD;
        PNES.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">December 1, 2023</start_date>
    <completion_date type="Anticipated">August 31, 2026</completion_date>
    <primary_completion_date type="Anticipated">August 31, 2026</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>Parallel Assignment</intervention_model>
      <intervention_model_description>Children with PNES and matched controls will be prospectively enrolled. PNES participants will be randomized to either supportive therapy or Retraining and Control Therapy (ReACT).</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Double (Investigator, Outcomes Assessor)</masking>
      <masking_description>Researchers who conduct baseline and follow-up visits will be blinded to the condition to which the patient has been assigned. The statistician and data manger will be blinded to treatment condition when analyzing data. The PI and therapists will be blinded to participant's baseline target scores.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Magic and turbulence task</measure>
      <time_frame>10 months</time_frame>
      <description>Measure of perceived sense of control in response to tasks in which control is manipulated; Greater negative numbers indicate improved understanding of control. Assessed at baseline visit, and 1 week and 6 months after the final therapy sessions (about 10 months total).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Pain catastrophizing scale for children- situation specific</measure>
      <time_frame>10 months</time_frame>
      <description>Measures catastrophic symptom expectations; score ranges from 0-52, higher scores indicate greater levels of pain-related anxiety. Assessment done after performing Cold Pressor Test. Assessed at baseline visit, and 1 week and 6 months after the final therapy sessions (about 10 months total).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Pain tolerance (time)</measure>
      <time_frame>10 months</time_frame>
      <description>Measures catastrophic symptom expectations. Measured by the total time the participant can keep their hand in cool water during the Cold Pressor Test. Shorter time indicates less pain tolerance. Assessed at baseline visit, and 1 week and 6 months after the final therapy sessions (about 10 months total).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Salivary Cortisol</measure>
      <time_frame>10 months</time_frame>
      <description>Measures catastrophic symptom expectations. Measured before and after the cold pressor test. Increased cortisol response indicate increased perceived pain severity. Assessed at baseline visit, and 1 week and 6 months after the final therapy sessions (about 10 months total).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Pain Rating Scale</measure>
      <time_frame>10 months</time_frame>
      <description>Measures perceived pain severity after the CPT; score ranges from 0-100. Higher scores indicate greater perceived pain severity. Assessed at baseline visit, and 1 week and 6 months after the final therapy sessions (about 10 months total).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Stroop task</measure>
      <time_frame>10 months</time_frame>
      <description>Measure of cognitive inhibition and selective attention, higher scores means poorer cognitive inhibition and selective attention. Assessed at baseline visit, and 1 week and 6 months after the final therapy sessions (about 10 months total).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>PNES Frequency</measure>
      <time_frame>16 months</time_frame>
      <description>Measured by Psychogenic Non-epileptic Seizures (PNES) diary, including frequency, premonitory symptoms, description of PNES symptoms and duration. Assessed 30 days before treatment to 12 months after the 12th treatment session (about 16 months total).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pain Catastrophizing Scale for Children (PCS-C)- General</measure>
      <time_frame>10 months</time_frame>
      <description>Measures catastrophic symptom expectations; score ranges from 0-52, higher scores indicate greater levels of pain-related anxiety. Assessment done before performing Cold Pressor Test. Assessed at baseline visit, and 1 week and 6 months after the final therapy sessions (about 10 months total).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Children's Somatic Symptoms Inventory (CSSI-24)</measure>
      <time_frame>16 months</time_frame>
      <description>General somatic symptom complaints, higher scores indicate greater somatic complaints. Scores range from 0-140. Completed by participant and parent. Assessed at baseline visit, and 1 week, 6 months and 12 months after the final therapy sessions (about 16 months total).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Anxiety Sensitivity Index (ASI)</measure>
      <time_frame>16 months</time_frame>
      <description>Assesses catastrophic symptom expectations; scores ranges from 0-64, higher scores indicate greater anxiety. Completed by participant and parent. Assessed at baseline visit, and 1 week, 6 months and 12 months after the final therapy sessions (about 16 months total).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Shipley</measure>
      <time_frame>At Baseline</time_frame>
      <description>Assesses verbal IQ; higher scores indicate greater verbal IQ. Completed by participant. Assessed at baseline visit.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Quality of Life in Epilepsy for Adolescents (QOLIE-AD-48)</measure>
      <time_frame>16 months</time_frame>
      <description>Assesses health-related quality of life for children with epilepsy (used in PNES participants by instructing them to consider their PNES when asked about &quot;seizures&quot;); score ranges from 0-100, higher scores indicate better functioning and well-being. Completed by participant. Assessed at baseline visit, and 1 week, 6 months and 12 months after the final therapy sessions (about 16 months total).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Sense of Agency Question</measure>
      <time_frame>16 months</time_frame>
      <description>Single question which asks &quot;How much control do you believe you have over your PNES?&quot;, scored using a 4-point Likert scale. Lower score indicates better control over PNES. Completed by participant. Assessed at baseline visit, and 1 week, 6 months and 12 months after the final therapy sessions (about 16 months total).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>LEVEL 2-Somatic Symptom report adapted from the Participant Health Questionnaire</measure>
      <time_frame>16 months</time_frame>
      <description>Measures symptom severity in children; scores ranges from 0-26, higher scores indicate greater symptom severity. Completed by participant and parent. Assessed at baseline visit, and 1 week, 6 months and 12 months after the final therapy sessions (about 16 months total).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Functional Disability Inventory (FDI)</measure>
      <time_frame>16 months</time_frame>
      <description>Completed by child and parent to measure physical functioning and disability in children with chronic pain; score ranges from 0-60, higher scores indicate greater perceived functional disability. Completed by participant and parent. Assessed at baseline visit, and 1 week, 6 months and 12 months after the final therapy sessions (about 16 months total).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The Impact on Family Scale</measure>
      <time_frame>16 months</time_frame>
      <description>Assesses parental perceptions of the impact of a child's medical condition on the family; higher scores indicate greater financial burden on the family. Assessed at baseline visit, and 1 week, 6 months and 12 months after the final therapy sessions (about 16 months total).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Childhood Trauma Questionnaire</measure>
      <time_frame>At baseline</time_frame>
      <description>History of physical, sexual and/or emotional abuse and physical and emotional neglect. All clinical subscales have a score range of 5-25, higher scores indicate greater abuse/neglect. Completed by participant. Assessed at baseline visit.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The Revised Children's Anxiety and Depression Scale (RCADS)</measure>
      <time_frame>16 months</time_frame>
      <description>Measures anxiety and depression symptoms in children; total score ranges from 0-141, higher scores indicate increased symptom severity. Completed by participant and parent. Assessed at baseline visit, and 1 week, 6 months and 12 months after the final therapy sessions (about 16 months total).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The Columbia Suicide Severity Rating Scale (C-SSRS)</measure>
      <time_frame>16 months</time_frame>
      <description>Measure that addresses the full range of suicidal thoughts and behaviors that suggest a person is at heightened risk of committing suicide; score ranges from 0-25, higher score indicates greater suicidal ideation intensity. Completed by trained research study coordinator.Assessed at baseline visit, and 1 week, 6 months and 12 months after the final therapy sessions (about 16 months total).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Healthcare Related Stigma Questionnaire</measure>
      <time_frame>At Baseline</time_frame>
      <description>Measures stigma in patients and their parents related to their interaction with health care; scores ranges from 0-64, higher scores indicate greater stigma. Completed by participant and parent. Assessed at baseline visit.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>COVID-19 Functional Neurological Disorders (FND) Questionnaire</measure>
      <time_frame>At Baseline</time_frame>
      <description>Assesses the effect of COVID-19 diagnosis in FND patients (not on a rating scale). Completed by children. Assessed at baseline visit.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Flanker Inhibitory Control and Attention Subtest</measure>
      <time_frame>10 months</time_frame>
      <description>Subtest of the National Institute of Health Toolbox Cognition Battery. Measures executive function and attention; higher scores indicate better performance. Completed by children. Assessed at 1st therapy session, and 1 week and 6 months after 12th therapy session (about 10 months total).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>List Sorting Working Memory Subtest</measure>
      <time_frame>10 months</time_frame>
      <description>Subtest of the National Institute of Health Toolbox Cognition Battery. Measures working memory; higher scores indicate better performance. Completed by children. Assessed at 1st therapy session, and 1 week and 6 months after 12th therapy session (about 10 months total).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pattern Comparison Processing Speed Subtest</measure>
      <time_frame>10 months</time_frame>
      <description>Subtest of the National Institute of Health Toolbox Cognition Battery. Measures processing speed; higher scores indicate better performance. Completed by children. Assessed at 1st therapy session, and 1 week and 6 months after 12th therapy session (about 10 months total).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dimensional Change Card Sort Subtest</measure>
      <time_frame>10 months</time_frame>
      <description>Subtest of the National Institute of Health Toolbox Cognition Battery. Measures executive function; higher scores indicate better performance. Completed by children. Assessed at 1st therapy session, and 1 week and 6 months after 12th therapy session (about 10 months total).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Picture Sequence Memory Subtest</measure>
      <time_frame>10 months</time_frame>
      <description>Subtest of the National Institute of Health Toolbox Cognition Battery. Measures episodic memory; higher scores indicate better performance. Completed by children. Assessed at 1st therapy session, and 1 week and 6 months after 12th therapy session (about 10 months total).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Sleep Duration</measure>
      <time_frame>4 months</time_frame>
      <description>Measures total sleep duration in a 24-hour day. Objectively measured using Respironics Actiwatch Spectrum Pro and subjectively measured using sleep diaries. Worn/completed by children. Assessed for 1 week between baseline visit and 1st therapy session and 2 weeks between 11th therapy session and 1 week after 12th therapy session (about 4 months total).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Sleep Efficiency</measure>
      <time_frame>4 months</time_frame>
      <description>Measures quality of sleep. Objectively measured using Respironics Actiwatch Spectrum Pro and subjectively measured using sleep diaries. Worn/completed by children. Assessed for 1 week between baseline visit and 1st therapy session and 2 weeks between 11th therapy session and 1 week after 12th therapy session (about 4 months total).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Sleep Onset Latency</measure>
      <time_frame>4 months</time_frame>
      <description>Refers to the time it took the child to fall asleep after lying down in bed. Objectively measured using Respironics Actiwatch Spectrum Pro and subjectively measured using sleep diaries. Worn/completed by children. Assessed for 1 week between baseline visit and 1st therapy session and 2 weeks between 11th therapy session and 1 week after 12th therapy session (about 4 months total).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Sleep - Bed Time</measure>
      <time_frame>5 months</time_frame>
      <description>Measures total time in bed in a 24-hour day. Objectively measured using Respironics Actiwatch Spectrum Pro and subjectively measured using sleep diaries. Worn/completed by children. Assessed for 1 week between baseline visit and 1st therapy session and 2 weeks between 11th therapy session and 1 week after 12th therapy session (about 5 months total).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Sleep - Wake Time</measure>
      <time_frame>4 months</time_frame>
      <description>Measures total awake time in a 24-hour day. Objectively measured using Respironics Actiwatch Spectrum Pro and subjectively measured using sleep diaries. Worn/completed by children. Assessed for 1 week between baseline visit and 1st therapy session and 2 weeks between 11th therapy session and 1 week after 12th therapy session (about 4 months total).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PNES Episode Frequency</measure>
      <time_frame>4 months</time_frame>
      <description>Measures the total number of PNES episodes the child had in a day. Objectively measured using Respironics Actiwatch Spectrum Pro. Worn by children. Assessed for 1 week between baseline visit and 1st therapy session and 2 weeks between 11th therapy session and 1 week after 12th therapy session (about 4 months total).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PNES Episode Duration</measure>
      <time_frame>4 months</time_frame>
      <description>Measures the duration of a PNES episode. Objectively measured using Respironics Actiwatch Spectrum Pro. Worn by children. Assessed for 1 week between baseline visit and 1st therapy session and 2 weeks between 11th therapy session and 1 week after 12th therapy session (about 4 months total).</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">160</enrollment>
    <condition>Convulsion, Non-Epileptic</condition>
    <arm_group>
      <arm_group_label>ReACT Intervention</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>At the end of the baseline visit, half of the participants will be randomized to receive Retraining and Control Therapy (ReACT)</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Supportive Therapy</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>At the end of the baseline visit, half of the participants will be randomized to receive supportive therapy</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Healthy Control</arm_group_label>
      <arm_group_type>No Intervention</arm_group_type>
      <description>Healthy controls are ages 12-18 with no significant comorbid medical or mental health conditions. Healthy controls and their parent come for 1 baseline laboratory visit and a follow up visit 13 weeks after the baseline visit. These visits will be identical to baseline and follow-up visits of children with PNES.</description>
    </arm_group>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>ReACT</intervention_name>
      <description>ReACT is a novel cognitive behavioral treatment and is a PNES intervention that targets sense of control and catastrophic symptom expectations. ReACT consists of 12 sessions of therapy focused on teaching adolescents to regain control of their body through managing thoughts and behaviors that reinforce the PNES and return to previous activities. It teaches parents how to respond to PNES in a manner that encourages the adolescents to regain control of their body. The PNES is explained as behaviors learned through classical and operant conditioning.</description>
      <arm_group_label>ReACT Intervention</arm_group_label>
      <other_name>Retraining and Control Therapy</other_name>
    </intervention>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>Supportive Therapy</intervention_name>
      <description>The supportive therapy treatment consists of 12 sessions of therapy focused on discussing daily difficulties and/or stressors they experience and identifying stress triggers for PNES. The PNES is explained as physical manifestations of psychological stress.</description>
      <arm_group_label>Supportive Therapy</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  11-18 years old.&#xD;
  &#xD;
            -  Diagnosis of psychogenic non-epileptic seizures by a medical doctor using video-EEG.&#xD;
  &#xD;
            -  Family member (parent/guardian if a minor) willing to participate and that the subject&#xD;
               with PNES chooses.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Comorbid Epilepsy&#xD;
  &#xD;
            -  Less than 4 PNES per month&#xD;
  &#xD;
            -  Other paroxysmal nonepileptic events (e.g. episodes related to hypoxic-ischemic&#xD;
               phenomena, sleep disorders or migraine-associated disorders)&#xD;
  &#xD;
            -  Participation in other therapy during the study&#xD;
  &#xD;
            -  Severe intellectual disability&#xD;
  &#xD;
            -  Severe mental illness (delusions/hallucinations)&#xD;
  &#xD;
          Exclusion for CPT:&#xD;
  &#xD;
            -  Blood pressure &gt;130/80 mmHg for adolescents greater than or equal to 13 years old&#xD;
  &#xD;
            -  Either systolic and/or diastolic blood pressure greater than or equal to 95% based on&#xD;
               sex and age for children less than 13 years old&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>11 Years</minimum_age>
      <maximum_age>18 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Aaron Fobian, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Alabama at Birmingham</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Aaron Fobian, PhD</last_name>
      <phone>205-934-2241</phone>
      <email>afobian@uabmc.edu</email>
    </overall_contact>
    <location>
      <facility>
        <name>University of Alabama at Birmingham</name>
        <address>
          <city>Birmingham</city>
          <state>Alabama</state>
          <zip>35294</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Badhma Valaiyapathi, MBBS, MPH</last_name>
        <phone>205-975-4205</phone>
        <email>drbadhma@uab.edu</email>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 11, 2023</study_first_submitted>
    <study_first_submitted_qc>August 17, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 23, 2023</study_first_posted>
    <last_update_submitted>August 22, 2023</last_update_submitted>
    <last_update_submitted_qc>August 22, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 24, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University of Alabama at Birmingham</investigator_affiliation>
      <investigator_full_name>Aaron Fobian</investigator_full_name>
      <investigator_title>Associate Professor</investigator_title>
    </responsible_party>
    <keyword>Supportive therapy</keyword>
    <keyword>ReACT</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Seizures</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06007053
  org study id: IRB-151001004
  nct id: NCT06007053
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  The purpose of this study is to assess sense of control and catastrophic symptom expectations
        as targets for Retraining and Control Therapy (ReACT- an intervention focused on changing
        behaviors and thoughts) for treatment of pediatric psychogenic non-epileptic seizures (PNES,
        episodes resembling epileptic seizures but with no correlated epileptiform activity).
        11-18-year-olds diagnosed with PNES will engage in twelve sessions of either ReACT or
        supportive therapy. Sense of control over actions will be measured by the magic and
        turbulence task, a well-validated measure of sense of control. Participants will complete the
        cold pressor test (CPT) in which participants hold their hand in cool water for as long as
        possible up to 3 minutes. Catastrophic symptom expectations in response to the CPT will be
        measured by Pain Catastrophizing Scale for Children (PCS-C), pain tolerance (time with hand
        in water) and cortisol response. Target assessments occur 7 days before treatment, 7 days
        after 12th treatment session, and 6 months after the 12th treatment session. PNES frequency
        will be measured from 30 days before to 6 months after treatment.
  Participants with PNES and their parent come to our laboratory for a baseline visit and 2
        follow-up visits. After the baseline visit, participants are randomized to 12 sessions of
        either Retraining and Control Therapy (ReACT) or supportive therapy. The first therapy
        session is in-person, and the following 11 sessions are completed via telehealth.
  
        During the baseline visit, participants and their parent complete several questionnaires
        assessing demographics, mood and suicidality, relationships with friends and family, as well
        as past and current PNES symptoms. They also complete the childhood trauma questionnaire. The
        treatment targets (sense of control and catastrophic symptom expectations) are measured by
        the magic and turbulence computer task and pain tolerance, PCS-C and cortisol response to the
        CPT, respectively. PNES diaries are completed to assess PNES frequency over the previous 30
        days. The baseline lab visit lasts about 2.5 hours. Saliva is collected over 3 time points
        before and after the CPT to measure cortisol response to the CPT. Participants also collect 2
        saliva samples 24 hours later to serve as a baseline outside of the laboratory setting.
        Participants will also be given a Respironics Actiwatch Spectrum Pro to track sleep and PNES
        episode severity and frequency for the 1 week between the baseline visit and first therapy
        session.
  
        After the baseline visit, participants are scheduled to return in one week for their first of
        12 intervention sessions of either ReACT or supportive therapy. This first session lasts a
        maximum of two hours, and the following 11 sessions are scheduled weekly and last one hour.
        The following 11 sessions are conducted as telehealth visits via HIPAA-compliant Zoom. Before
        beginning the first ReACT session, participants will complete the Flanker Inhibitory Control
        and Attention, List Sorting Working Memory, Pattern Comparison Processing Speed, Dimensional
        Change Card Sort, and Picture Sequence Memory subtests. Participants will be mailed another
        Respironics Actiwatch Spectrum Pro before the 11th therapy session to track sleep and PNES
        episode severity and frequency for the 2 weeks between the 11th therapy session and the lab
        visit one week after the 12th treatment session.
  
        Follow-up at 7 days after treatment and 6 months after treatment also is conducted to perform
        tasks and complete follow-up assessment of the targets (sense of control and catastrophic
        symptom expectations), PNES frequency, and questionnaires. Each of these sessions last 2
        hours. Participants will complete the Flanker Inhibitory Control and Attention, List Sorting
        Working Memory, Pattern Comparison Processing Speed, Dimensional Change Card Sort, and
        Picture Sequence Memory subtests at the lab visit at each of these visits. A Zoom visit will
        be completed at 12 months after treatment to assess long-term PNES outcomes and questionnaire
        data. This appointment will last 1 hour. PNES frequency will be measured from 30 days before
        treatment to 12 months after treatment through PNES diaries completed by the parent and the
        participant.
  
        Participants will be offered the treatment to which they were not randomized after the
        6-month follow-up when the study is completed.
  
        After treatment, booster therapy sessions will be offered as needed.
  
        Healthy controls will be recruited. Healthy controls and their parent come for a baseline
        laboratory visit and a follow up visit 13 weeks after the baseline visit. The baseline and
        follow-up appointments for healthy controls will be identical to the visits for children with
        PNES.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Children with PNES and matched controls will be prospectively enrolled. PNES participants will be randomized to either supportive therapy or Retraining and Control Therapy (ReACT).
  primary purpose: Treatment
  masking: Double (Investigator, Outcomes Assessor)
  masking description: Researchers who conduct baseline and follow-up visits will be blinded to the condition to which the patient has been assigned. The statistician and data manger will be blinded to treatment condition when analyzing data. The PI and therapists will be blinded to participant's baseline target scores.
  measure: Magic and turbulence task
  time frame: 10 months
  description: Measure of perceived sense of control in response to tasks in which control is manipulated; Greater negative numbers indicate improved understanding of control. Assessed at baseline visit, and 1 week and 6 months after the final therapy sessions (about 10 months total).
  measure: Pain catastrophizing scale for children- situation specific
  time frame: 10 months
  description: Measures catastrophic symptom expectations; score ranges from 0-52, higher scores indicate greater levels of pain-related anxiety. Assessment done after performing Cold Pressor Test. Assessed at baseline visit, and 1 week and 6 months after the final therapy sessions (about 10 months total).
  measure: Pain tolerance (time)
  time frame: 10 months
  description: Measures catastrophic symptom expectations. Measured by the total time the participant can keep their hand in cool water during the Cold Pressor Test. Shorter time indicates less pain tolerance. Assessed at baseline visit, and 1 week and 6 months after the final therapy sessions (about 10 months total).
  measure: Salivary Cortisol
  time frame: 10 months
  description: Measures catastrophic symptom expectations. Measured before and after the cold pressor test. Increased cortisol response indicate increased perceived pain severity. Assessed at baseline visit, and 1 week and 6 months after the final therapy sessions (about 10 months total).
  measure: Pain Rating Scale
  time frame: 10 months
  description: Measures perceived pain severity after the CPT; score ranges from 0-100. Higher scores indicate greater perceived pain severity. Assessed at baseline visit, and 1 week and 6 months after the final therapy sessions (about 10 months total).
  measure: Stroop task
  time frame: 10 months
  description: Measure of cognitive inhibition and selective attention, higher scores means poorer cognitive inhibition and selective attention. Assessed at baseline visit, and 1 week and 6 months after the final therapy sessions (about 10 months total).
  measure: PNES Frequency
  time frame: 16 months
  description: Measured by Psychogenic Non-epileptic Seizures (PNES) diary, including frequency, premonitory symptoms, description of PNES symptoms and duration. Assessed 30 days before treatment to 12 months after the 12th treatment session (about 16 months total).
  measure: Pain Catastrophizing Scale for Children (PCS-C)- General
  time frame: 10 months
  description: Measures catastrophic symptom expectations; score ranges from 0-52, higher scores indicate greater levels of pain-related anxiety. Assessment done before performing Cold Pressor Test. Assessed at baseline visit, and 1 week and 6 months after the final therapy sessions (about 10 months total).
  measure: Children's Somatic Symptoms Inventory (CSSI-24)
  time frame: 16 months
  description: General somatic symptom complaints, higher scores indicate greater somatic complaints. Scores range from 0-140. Completed by participant and parent. Assessed at baseline visit, and 1 week, 6 months and 12 months after the final therapy sessions (about 16 months total).
  measure: Anxiety Sensitivity Index (ASI)
  time frame: 16 months
  description: Assesses catastrophic symptom expectations; scores ranges from 0-64, higher scores indicate greater anxiety. Completed by participant and parent. Assessed at baseline visit, and 1 week, 6 months and 12 months after the final therapy sessions (about 16 months total).
  measure: Shipley
  time frame: At Baseline
  description: Assesses verbal IQ; higher scores indicate greater verbal IQ. Completed by participant. Assessed at baseline visit.
  measure: Quality of Life in Epilepsy for Adolescents (QOLIE-AD-48)
  time frame: 16 months
  description: Assesses health-related quality of life for children with epilepsy (used in PNES participants by instructing them to consider their PNES when asked about "seizures"); score ranges from 0-100, higher scores indicate better functioning and well-being. Completed by participant. Assessed at baseline visit, and 1 week, 6 months and 12 months after the final therapy sessions (about 16 months total).
  measure: Sense of Agency Question
  time frame: 16 months
  description: Single question which asks "How much control do you believe you have over your PNES?", scored using a 4-point Likert scale. Lower score indicates better control over PNES. Completed by participant. Assessed at baseline visit, and 1 week, 6 months and 12 months after the final therapy sessions (about 16 months total).
  measure: LEVEL 2-Somatic Symptom report adapted from the Participant Health Questionnaire
  time frame: 16 months
  description: Measures symptom severity in children; scores ranges from 0-26, higher scores indicate greater symptom severity. Completed by participant and parent. Assessed at baseline visit, and 1 week, 6 months and 12 months after the final therapy sessions (about 16 months total).
  measure: Functional Disability Inventory (FDI)
  time frame: 16 months
  description: Completed by child and parent to measure physical functioning and disability in children with chronic pain; score ranges from 0-60, higher scores indicate greater perceived functional disability. Completed by participant and parent. Assessed at baseline visit, and 1 week, 6 months and 12 months after the final therapy sessions (about 16 months total).
  measure: The Impact on Family Scale
  time frame: 16 months
  description: Assesses parental perceptions of the impact of a child's medical condition on the family; higher scores indicate greater financial burden on the family. Assessed at baseline visit, and 1 week, 6 months and 12 months after the final therapy sessions (about 16 months total).
  measure: Childhood Trauma Questionnaire
  time frame: At baseline
  description: History of physical, sexual and/or emotional abuse and physical and emotional neglect. All clinical subscales have a score range of 5-25, higher scores indicate greater abuse/neglect. Completed by participant. Assessed at baseline visit.
  measure: The Revised Children's Anxiety and Depression Scale (RCADS)
  time frame: 16 months
  description: Measures anxiety and depression symptoms in children; total score ranges from 0-141, higher scores indicate increased symptom severity. Completed by participant and parent. Assessed at baseline visit, and 1 week, 6 months and 12 months after the final therapy sessions (about 16 months total).
  measure: The Columbia Suicide Severity Rating Scale (C-SSRS)
  time frame: 16 months
  description: Measure that addresses the full range of suicidal thoughts and behaviors that suggest a person is at heightened risk of committing suicide; score ranges from 0-25, higher score indicates greater suicidal ideation intensity. Completed by trained research study coordinator.Assessed at baseline visit, and 1 week, 6 months and 12 months after the final therapy sessions (about 16 months total).
  measure: Healthcare Related Stigma Questionnaire
  time frame: At Baseline
  description: Measures stigma in patients and their parents related to their interaction with health care; scores ranges from 0-64, higher scores indicate greater stigma. Completed by participant and parent. Assessed at baseline visit.
  measure: COVID-19 Functional Neurological Disorders (FND) Questionnaire
  time frame: At Baseline
  description: Assesses the effect of COVID-19 diagnosis in FND patients (not on a rating scale). Completed by children. Assessed at baseline visit.
  measure: Flanker Inhibitory Control and Attention Subtest
  time frame: 10 months
  description: Subtest of the National Institute of Health Toolbox Cognition Battery. Measures executive function and attention; higher scores indicate better performance. Completed by children. Assessed at 1st therapy session, and 1 week and 6 months after 12th therapy session (about 10 months total).
  measure: List Sorting Working Memory Subtest
  time frame: 10 months
  description: Subtest of the National Institute of Health Toolbox Cognition Battery. Measures working memory; higher scores indicate better performance. Completed by children. Assessed at 1st therapy session, and 1 week and 6 months after 12th therapy session (about 10 months total).
  measure: Pattern Comparison Processing Speed Subtest
  time frame: 10 months
  description: Subtest of the National Institute of Health Toolbox Cognition Battery. Measures processing speed; higher scores indicate better performance. Completed by children. Assessed at 1st therapy session, and 1 week and 6 months after 12th therapy session (about 10 months total).
  measure: Dimensional Change Card Sort Subtest
  time frame: 10 months
  description: Subtest of the National Institute of Health Toolbox Cognition Battery. Measures executive function; higher scores indicate better performance. Completed by children. Assessed at 1st therapy session, and 1 week and 6 months after 12th therapy session (about 10 months total).
  measure: Picture Sequence Memory Subtest
  time frame: 10 months
  description: Subtest of the National Institute of Health Toolbox Cognition Battery. Measures episodic memory; higher scores indicate better performance. Completed by children. Assessed at 1st therapy session, and 1 week and 6 months after 12th therapy session (about 10 months total).
  measure: Sleep Duration
  time frame: 4 months
  description: Measures total sleep duration in a 24-hour day. Objectively measured using Respironics Actiwatch Spectrum Pro and subjectively measured using sleep diaries. Worn/completed by children. Assessed for 1 week between baseline visit and 1st therapy session and 2 weeks between 11th therapy session and 1 week after 12th therapy session (about 4 months total).
  measure: Sleep Efficiency
  time frame: 4 months
  description: Measures quality of sleep. Objectively measured using Respironics Actiwatch Spectrum Pro and subjectively measured using sleep diaries. Worn/completed by children. Assessed for 1 week between baseline visit and 1st therapy session and 2 weeks between 11th therapy session and 1 week after 12th therapy session (about 4 months total).
  measure: Sleep Onset Latency
  time frame: 4 months
  description: Refers to the time it took the child to fall asleep after lying down in bed. Objectively measured using Respironics Actiwatch Spectrum Pro and subjectively measured using sleep diaries. Worn/completed by children. Assessed for 1 week between baseline visit and 1st therapy session and 2 weeks between 11th therapy session and 1 week after 12th therapy session (about 4 months total).
  measure: Sleep - Bed Time
  time frame: 5 months
  description: Measures total time in bed in a 24-hour day. Objectively measured using Respironics Actiwatch Spectrum Pro and subjectively measured using sleep diaries. Worn/completed by children. Assessed for 1 week between baseline visit and 1st therapy session and 2 weeks between 11th therapy session and 1 week after 12th therapy session (about 5 months total).
  measure: Sleep - Wake Time
  time frame: 4 months
  description: Measures total awake time in a 24-hour day. Objectively measured using Respironics Actiwatch Spectrum Pro and subjectively measured using sleep diaries. Worn/completed by children. Assessed for 1 week between baseline visit and 1st therapy session and 2 weeks between 11th therapy session and 1 week after 12th therapy session (about 4 months total).
  measure: PNES Episode Frequency
  time frame: 4 months
  description: Measures the total number of PNES episodes the child had in a day. Objectively measured using Respironics Actiwatch Spectrum Pro. Worn by children. Assessed for 1 week between baseline visit and 1st therapy session and 2 weeks between 11th therapy session and 1 week after 12th therapy session (about 4 months total).
  measure: PNES Episode Duration
  time frame: 4 months
  description: Measures the duration of a PNES episode. Objectively measured using Respironics Actiwatch Spectrum Pro. Worn by children. Assessed for 1 week between baseline visit and 1st therapy session and 2 weeks between 11th therapy session and 1 week after 12th therapy session (about 4 months total).
  arm group label: ReACT Intervention
  arm group type: Experimental
  description: At the end of the baseline visit, half of the participants will be randomized to receive Retraining and Control Therapy (ReACT)
  arm group label: Supportive Therapy
  arm group type: Active Comparator
  description: At the end of the baseline visit, half of the participants will be randomized to receive supportive therapy
  arm group label: Healthy Control
  arm group type: No Intervention
  description: Healthy controls are ages 12-18 with no significant comorbid medical or mental health conditions. Healthy controls and their parent come for 1 baseline laboratory visit and a follow up visit 13 weeks after the baseline visit. These visits will be identical to baseline and follow-up visits of children with PNES.
  intervention type: Behavioral
  intervention name: ReACT
  description: ReACT is a novel cognitive behavioral treatment and is a PNES intervention that targets sense of control and catastrophic symptom expectations. ReACT consists of 12 sessions of therapy focused on teaching adolescents to regain control of their body through managing thoughts and behaviors that reinforce the PNES and return to previous activities. It teaches parents how to respond to PNES in a manner that encourages the adolescents to regain control of their body. The PNES is explained as behaviors learned through classical and operant conditioning.
  arm group label: ReACT Intervention
  other name: Retraining and Control Therapy
  intervention type: Behavioral
  intervention name: Supportive Therapy
  description: The supportive therapy treatment consists of 12 sessions of therapy focused on discussing daily difficulties and/or stressors they experience and identifying stress triggers for PNES. The PNES is explained as physical manifestations of psychological stress.
  arm group label: Supportive Therapy
  criteria: 
  gender: All
  minimum age: 11 Years
  maximum age: 18 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Aaron Fobian, PhD
  role: Principal Investigator
  affiliation: University of Alabama at Birmingham
  last name: Aaron Fobian, PhD
  phone: 205-934-2241
  email: afobian@uabmc.edu
  facility: 
  contact: 
  country: United States
  responsible party type: Principal Investigator
  investigator affiliation: University of Alabama at Birmingham
  investigator full name: Aaron Fobian
  investigator title: Associate Professor
  mesh term: Seizures