A Multi-site Feasibility Clinical Trial of Retraining and Control Therapy (ReACT), a Mind and Body Treatment for Pediatric Functional Seizures

Study Overview
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Brief Summary
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The purpose of this study is to assess the feasibility of conducting a future fully powered multi-site efficacy Randomized Controlled Trial (RCT) comparing two treatments for pediatric functional seizures (FS). In this study, 11-18-year-olds diagnosed with FS will be randomized to 12 sessions of Retraining and Control Therapy (ReACT) or Competent Adulthood Transition with Cognitive Behavioral, Humanistic, and Interpersonal Training (CATCH-IT) at 3 sites: University of Alabama at Birmingham, Yale School of Medicine/Yale New Haven Children's Hospital and Baylor College of Medicine/Texas Children's Hospital. Feasibility of recruitment will be measured by the percentage of planned participant enrollment target obtained at each site and overall during the 18 months of planned enrollment. Acceptability will be assessed using the Acceptability Questionnaire. Participant retention will be measured by the percent of enrolled participants that complete the 2-month follow-up visit at each site and overall. For treatment fidelity assessment, 20% of each therapist's sessions will be randomly chosen and assessed for fidelity. Patient adherence will be measured in two ways: 1) the percent of ReACT or CATCH-IT sessions completed at each site and overall and 2) for ReACT, the percent of times participants report using the treatment plan during FS episodes (measured by FS diary) and for CATCH-IT, the number of times parents and children spend using CATCH-IT each week (measured by the CATCH-IT platform). These data will be used to support a future fully-powered multi-site RCT assessing the efficacy of ReACT for pediatric FS.

Detailed Description
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This study aims to conduct a multi-site pilot feasibility Randomized Controlled Trial (RCT) at the University of Alabama at Birmingham, Yale College of Medicine/Yale New Haven Children's Hospital and Baylor College of Medicine/Texas Children's Hospital. Participants with functional seizures (FS) will be screened for eligibility over a phone call and eligible participants will be invited for a baseline visit. Participants with FS and their parent/guardian will then complete a baseline visit and 2 follow-up visits via HIPAA-compliant Zoom, 1 in-person initial therapy session and 11 video telehealth follow-up therapy sessions via HIPAA-compliant Zoom. During the initial baseline visit, participants and their family member/caregiver will complete several questionnaires assessing demographics, mood, relationships with friends and family, as well as past and current FS symptoms. Participants will receive a functional seizure diary to record all episodes during the course of the study. This visit will last about an hour and a half. They will then be randomized to 12 sessions of either Competent Adulthood Transition with Cognitive Behavioral, Humanistic, and Interpersonal Training (CATCH-IT) or Retraining and Control Therapy (ReACT). CATCH-IT involves the parent and child completing Cognitive Behavioral Therapy (CBT) modules on the web-based CATCH-IT platform, and they will meet with a CATCH-IT coach 12 times to discuss the modules and plan how to apply this to their life and their FS. ReACT includes 12 sessions with a therapist that will discuss a plan for managing FS. The first session for each intervention will be in-person with the subsequent 11 sessions conducted via video telehealth. Individual study teams from the 3 participating sites will conduct the ReACT or CATCH-IT interventions at their respective sites. The first therapy session will last about 2 hours and the subsequent 11 telehealth sessions will last about an hour. There will be 2 follow-up visits via HIPAA-compliant Zoom which will follow the same protocol as the baseline visit. The first follow-up visit will be one week after the 12th therapy session, and the second follow-up visit will be two months after the 12th therapy session. Both these sessions will last about an hour. Participants will also have the opportunity to undergo the therapy to which they were not randomized to at the end of the study.

Official Title
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A Multi-site Feasibility Clinical Trial of Retraining and Control Therapy (ReACT), a Mind and Body Treatment for Pediatric Functional Seizures

Conditions
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Functional Seizures, Convulsion, Non-Epileptic

Intervention / Treatment
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* Behavioral: ReACT
* Behavioral: CATCH-IT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females ages 11-18 Diagnosis of functional seizures Internet access for telehealth sessions and CATCH-IT Exclusion Criteria: Comorbid epilepsy Less than 4 functional seizures per month Other paroxysmal nonepileptic events (e.g. hypoxic-ischemic phenomena, sleep disorders or migraine-associated disorders) Participation in other therapy Severe intellectual disability Severe mental illness (active delusions/hallucinations)

Ages Eligible for Study
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Minimum Age: 11 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Children with FS will be enrolled and randomized to either ReACT or CATCH-IT therapies
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ReACT Intervention<br>During the initial visit participant will be randomized to either Retraining and Control Therapy (ReACT) or Competent Adulthood Transition with Cognitive Behavioral, Humanistic, and Interpersonal Training (CATCH-IT) intervention. ReACT includes 12 sessions with a therapist that will discuss a plan for managing FS. Participants will have 12 therapy sessions. The first session will be in-person which will last 2 hours and the subsequent 11 sessions will be conducted via video telehealth and each session will last 1 hour. | Behavioral: ReACT<br>* ReACT includes 12 sessions with a therapist that will discuss a plan for managing FS.<br>* Other names: Retraining and Control Therapy;|
| Active Comparator: CATCH-IT Intervention<br>During the initial visit participant will be randomized to either Retraining and Control Therapy (ReACT) or Competent Adulthood Transition with Cognitive Behavioral, Humanistic, and Interpersonal Training (CATCH-IT) intervention. CATCH-IT involves the parent and child completing CBT modules on the web-based CATCH-IT platform, and they will meet with a CATCH-IT coach 12 times to discuss the modules and plan how to apply this to their life and their FS. Participants will have 12 therapy sessions. The first session will be in-person which will last 2 hours and the subsequent 11 sessions will be conducted via video telehealth and each session will last 1 hour. | Behavioral: CATCH-IT<br>* CATCH-IT involves the parent and child completing CBT modules on the web-based CATCH-IT platform, and they will meet with a CATCH-IT coach 12 times to discuss the modules and plan how to apply this to their life and their FS.<br>* Other names: Competent Adulthood Transition with Cognitive Behavioral, Humanistic, and Interpersonal Training;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of Recruitment | Feasibility of recruitment will be measured by the percentage of the planned participant enrollment target obtained at each site and overall during the 18 months of planned enrollment. This includes any participant who completes informed consent/assent. | 18 months | 
| Treatment Fidelity | Fidelity will be stratified by site and therapist/coach, such that 20% of each therapist/coach's sessions will be randomly chosen for fidelity assessment. The ReACT Fidelity Rating Scale includes assessment of the therapists' correct use of the ReACT Treatment Determination Tool, therapeutic alliance and empathy with the patient and family, development of opposing responses and use of motivators to reinforce progress. Fidelity to CATCH-IT sessions will be measured by the CATCH-IT coach fidelity scale, which assesses conduct of the motivational interview, review of the CATCH-IT sessions, therapeutic alliance and empathy with the patient and family. | 18 months | 
| Participant Adherence | Patient adherence will be measured in two ways: 1) the percent of ReACT or CATCH-IT sessions completed at each site and overall and 2) for ReACT, the percent of times participants report using the treatment plan during FS episodes (measured by FS diary) and for CATCH-IT, the number of times parents and children spend using CATCH-IT each week (measured by the CATCH-IT platform). | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participant Retention | With the goal of analyzing data from the subsequent efficacy trial with an intention-to-treat analysis, participant retention will be measured by the percent of enrolled participants that complete the 2-month follow-up visit at each site and overall. | 18 months | 
| Acceptability | Acceptability will be assessed using the Acceptability Questionnaire. The Acceptability Questionnaire is based on a published theoretical framework for assessment of acceptability of healthcare interventions and assesses acceptability of being randomized to ReACT vs. CATCH-IT, acceptability of the treatment received and presence of treatment side effects associated with ReACT or CATCH-IT, including all side effects associated with mindfulness. For each reported side effect, the duration, tolerability, perceived unpleasantness, impact on functioning and acceptability based on treatment benefit will be obtained. | 18 months | 
| Functional seizure frequency | FS Diaries will be completed in REDCap by parents and children to prospectively track FS frequency from 7 days prior to treatment through 2 months post treatment, including date, time, location, duration and nature of symptoms. Those in ReACT will report if they used their treatment plan for each FS and track each FS they prevented with the plan. They will retrospectively report FS for the 3 weeks prior to initial screening. Discrepancies in parent and adolescent report will be discussed and rectified to improve accuracy | 7 months | 
| Sense of Agency scale | Sense of Control Scale is a single question which asks, How much control do you believe you have over your FS? at baseline and post follow-up visits. Scores range from 0-3 with a higher score indicating no control over functional seizures. | 5 to 7 months | 
| Treatment Preference Questionnaire | Treatment Preference Questionnaire will be completed before randomization to assess to which treatment the participant and parent prefer to be randomized. This is a single question which asks the participant Which treatment would they prefer to be randomized to?. | Baseline Visit | 
| Quality of Life in Epilepsy for Adolescents (QOLIE-AD-48) | Quality of Life in Epilepsy for Adolescents (QOLIE-AD-48) is a survey of health-related quality of life for children with epilepsy with higher scores indicating a poor quality of life. It is used in patients with FS by instructing them to consider their FS when asked about seizures. Scores range from 0-100. This will be completed at baseline and follow-up visits. | 5 to 7 months | 
| Revised Helping Alliance Questionnaire- II | Revised Helping Alliance Questionnaire-II is a 19-item scale will assess the therapist, children and parents' perception of the therapeutic alliance at follow-ups. Scores ranges from 19-114 with a higher score indicating better therapeutic alliance. | 5 to 7 months | 
| The Credibility/Expectancy Questionnaire | The Credibility/Expectancy Questionnaire will be used to compare treatment expectancy between conditions. It measures how much the patient believes the therapy they are receiving will help to reduce their FS. This will be completed initially after being randomized, after the first session and at the follow-up visits. | 5 to 7 months | 
| Children's Somatic Symptoms Inventory (CSSI-24) | 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 follow-up visits | 5 to 7 months | 
| Anxiety Sensitivity Index (ASI) | Assesses catastrophic symptom expectations; higher scores indicate greater anxiety. Completed by the parent. Assessed at baseline visit and follow-up visits | 5 to 7 months | 
| LEVEL 2-Somatic Symptom report adapted from the Participant Health Questionnaire | Measures symptom severity in children; higher scores indicate greater symptom severity. Completed by participant and parent. Assessed at baseline visit and follow-up visits. | 5 to 7 months | 
| Functional Disability Inventory (FDI) | 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 follow-up visits | 5 to 7 months | 
| The Impact on Family Scale | 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 follow-up visits. | 5 to 7 months | 
| The Revised Children's Anxiety and Depression Scale (RCADS) | Measures anxiety and depression symptoms in children; higher scores indicate increased symptom severity. Completed by participant and parent. Assessed at baseline visit and follow-up visits | 5 to 7 months | 
| Healthcare Related Stigma Questionnaire | Measures stigma in patients and their parents related to their interaction with health care providers; higher scores indicate greater stigma. Completed by participant and parent. Assessed at baseline visit. | At Baseline visit | 
| Childhood Anxiety Sensitivity Index (CASI) | Assesses catastrophic symptom expectations; higher scores indicate greater anxiety. Score ranges from 18-54. Completed by participant. Assessed at baseline visit and follow-up visits | 5 to 7 months | 
| Dysfunctional Attitude Scale (DAS-9) | Participant will complete this 9-item self-report measure that aims to determine stable negative attitudes that people with depression hold about themselves, the world, and their future. Assessed at baseline visit and follow-up visits. | 5 to 7 months | 
| Behavior Rating Inventory of Executive Functioning (BRIEF) | Assesses executive function and self-regulation in children and teens. Completed by participant at baseline visit and follow-up visits. | 5 to 7 months | 
| Beaver's Self-Report Family Inventory | This is a 36 item scale which assesses a family member's view of overall family competence. Completed by participant and parent. Assessed at baseline visit and follow-up visits. | 5 to 7 months | 
| FND Locus of Control: Multidimensional Health Locus of Control (MHLC) Scales | Measures an individual's belief in his/her ability to control health outcomes. Form C of MHLC scale will be completed by participant and Form A of MHLC scale will be completed by parent. Assessed at baseline visit and follow-up visits. | 5 to 7 months | 
| Rosenberg Self-esteem scale | This is a 10-item scale measuring self esteem. Score ranges from 0-30 with low scores indicating low self-esteem. Completed by participant at baseline visit and follow-up visits. | 5 to 7 months | 
| Mishel Uncertainty in Illness Questionnaire-Community Form (MUIS-C) | Participant will complete this 23-item scale which measures uncertainty about their diagnosis. Assessed at baseline visit and follow-up visits. | 5 to 7 months | 
| Illness Cognitions Scale | Participant will complete this 17-item scale measuring the degree to which they align with the sick role. Assessed at baseline visit and follow-up visits. | 5 to 7 months | 
| Center for Epidemiological Studies Depression Scale (CES-D) | Parent will complete this 10-item self-report depression inventory. Score ranges from 0 to 30 with higher scores indicating increasing levels of depression. Assessed at baseline visit and follow-up visits. | 5 to 7 months | 
| Center for Epidemiological Studies Depression Scale for Children (CES-DC) | Participant will complete this 20-item self-report depression inventory. Score ranges from 0 to 60 with higher scores indicating increasing levels of depression. Assessed at baseline visit and follow-up visits. | 5 to 7 months | 
| Parenting Style and Dimensions Questionnaire (PSDQ Short Version) | This is a 32-item scale assessing parenting style. Completed by parent at baseline visit and follow-up visits. | 5 to 7 months | 
| Session Summary Sheet (SSS) | Assesses parent and participant's therapeutic relationship, mastery of skill and involvement in therapy session. Completed by therapist at each intervention visit. | 5 to 7 months |