Epilepsy Journey-An Executive Functioning Intervention for Teens With Epilepsy

Not Applicable

Recruiting

• Conditions: Epilepsy in Children; Executive Dysfunction
• Interventions: Behavioral: Epilepsy Journey web-based modules; Behavioral: Telehealth with a therapist

• Registration Number: NCT06608966
• Lead Sponsor: Children's Hospital Medical Center, Cincinnati

Brief Summary

The goal of this multi-site clinical trial is to determine the effectiveness of two components of a web-based intervention (Epilepsy Journey) to improve executive functioning in adolescents with epilepsy. The two components include web-based modules and problem-solving telehealth sessions with a therapist focused on executive functioning. The main questions this trial aims to answer the following questions:

1. Which components of Epilepsy Journey (web-based modules or teleheath sessions with a therapist) are essential for improving executive functioning in adolescents with epilepsy?

2. Which components of Epilepsy Journey (web-based modules or teleheath sessions with a therapist) are essential for improving quality of life in adolescents with epilepsy?

Participants will be randomly assigned to one of four groups: 1) Epilepsy Journey web-based modules and telehealth sessions, 2) Epilepsy Journey web-based modules only, 3) telehealth sessions with a therapist only, or 4) treatment as usual.

Participants will:

* Independently review Epilepsy Journey web-based modules focused on executive functioning skills (\~15-30 minutes) and/or have weekly telehealth sessions (\~30-45 minutes) with a therapist for 14 weeks.

* Complete measures of executive functioning (parent and teen-report) and quality of life (teen-report) at the start of the study, 14-, 26-, and 66- weeks after randomization. The NIH toolbox will be completed at the start of the study and 26-weeks after randomization. Additional measures will also be collected.

Detailed Description

Epilepsy is a common pediatric neurological condition affecting \~470,000 youth in the United States. Adolescents with epilepsy are at significant risk for neurobehavioral comorbidities (i.e., depressive/behavioral symptoms) and suboptimal social, academic, and quality of life outcomes. Research suggests that deficits in executive functioning (EF), defined as the skills necessary for goal-directed and complex activities, including problem-solving, initiation, monitoring, organization, planning, self-regulation and working memory, contribute to suboptimal functioning. EF deficits have been documented in up to 50% of youth with epilepsy, which is 3 times the prevalence in healthy youth. Evidence-based interventions to improve EF could play a critical role in preventing adverse outcomes and promoting optimal functioning in adolescents with epilepsy; however none exists for this vulnerable population. To fill this gap, we successfully developed and tested Epilepsy Journey (EJ), a comprehensive e-health behavioral multi-component problem-solving intervention that combines 10 self-guided learning modules with 10 telehealth sessions. The promising proof-of-concept trial (n=39) showed high feasibility, acceptability, patient satisfaction, and significant improvements in parent-reported EF behaviors, neurobehavioral functioning, and quality of life. The next logical phase of this research is to conduct a definitive randomized clinical trial to examine: whether the two components of treatment (EJ modules and telehealth) are 1) both essential and 2) have a durable impact on improving parent-reported and performance-based EF behaviors and quality of life. Thus, the aim of the current proposal is to conduct a multi-site Phase 3 randomized controlled clinical trial (RCT) using a 2x2 factorial design to examine the efficacy of separate (EJ modules and EJ telehealth) and combined components of EJ on EF. Participants positive for EF deficits (n=232) will be randomized to one of four arms: 1) EJ modules with telehealth sessions, 2) EJ modules alone, 3) EJ telehealth sessions alone, or 4) Usual Care (no EJ modules or telehealth sessions). Treatment participants will either independently review EJ modules focused on EF skills (\~15-30 min.) and/or have weekly telehealth sessions (\~30-45 min.) with a therapist for 14-weeks. The groups will learn and apply problem-solving strategies to their individual EF difficulties. Participants will complete measures at baseline, 14-, 26-, and 66- weeks after randomization to examine maintenance of effects. There is a critical need for evidence-based interventions to improve executive functioning behaviors in youth with epilepsy. If the aims of this study are achieved, we will have definitive evidence for addressing EF deficits. We expect that EJ modules and EJ telehealth will demonstrate efficacy alone and in combination, which will allow patients to select the approach best suited to their specific situation. Consequently, we can improve long-term outcomes (e.g., neurobehavioral comorbidities, academic success, social relationships, and quality of life) in adolescents with epilepsy, a high-risk population.

Study Timeline

• Study First Submitted: 2024-09-20
• Study First Submitted QC: 2024-09-20
• Study First Posted: 2024-09-23
• Study Start: 2024-11-11
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-24
• Last Update Posted: 2025-04-25
• Primary Completion: 2028-10-31
• Study Completion: 2029-01-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 310

Inclusion Criteria

1. Age between 13-17 years at the time of enrollment
2. Child lives at home with primary caregiver and is enrolled in school (excluding summer breaks).
3. Confirmed diagnosis of epilepsy with seizures that are categorized as either generalized or focal in onset. Epilepsy is defined as: 1) At least two unprovoked seizures occurring more than 24-hours apart; or 2) One unprovoked seizure and a probability of further seizures similar to the general recurrence risk after two unprovoked seizures.
4. Primary language of English
5. Screening Inclusion: On the parent-reported Behavior Rating Inventory of Executive Function-2nd edition (BRIEF-2), have executive functioning deficits defined as at least 2 subclinical (60<T<65) or one clinical BRIEF-2 subscale T scores (T≥65).
6. Parent/legal guardian(s) willing to sign an IRB approved informed consent
7. Participant willing to sign an Institutional Review Board approved assent

Exclusion Criteria

1. Parent or clinician-reported history in the adolescent of:

   1. developmental delay (e.g., autism spectrum disorder, pervasive development disorder, history of services for developmental delay or intellectual impairment in the past 5 years, known IQ<70)
   2. severe mental illness (e.g., schizophrenia, bipolar disorder, eating disorder within the past 12 months, depression with active suicidal ideation or suicidal ideation/intent in the past 3 months)
   3. prior (3-months) or current history of trauma and/or stressor-related disorders (e.g. PTSD)
   4. recent or current significant medical disease (i.e., cardiovascular, hepatic, renal, gynecologic, musculoskeletal, metabolic or endocrine)
   5. brain injury or brain tumor; and/or
   6. epilepsy surgery
   7. any other medical and/or psychological condition that takes treatment precedence over the study intervention

2. Clinician-reported diagnosis in the adolescent of

   1. epilepsy whose seizures are categorized only as either unknown onset or unclassified onset (defined as insufficient information to determine onset)
   2. epilepsy currently being treated at the time of enrollment by 3 or more antiseizure medications (ASMs) (excluding rescue medication use)
   3. epilepsy with a history of failure to achieve seizure freedom despite adequate use of 4 different anti-seizure medications
   4. a confirmed or suspected epileptic encephalopathy (e.g., electrical status epilepticus in sleep, Landau Kleffner syndrome, West syndrome)
   5. a confirmed or suspected progressive and degenerative disorder (e.g., mitochondrial disorders, metabolic disorders, autoimmune disorders)
   6. one or more episodes of status epilepticus within the 24 weeks prior to enrollment; and/or
   7. treatable causes of seizures, for example identified etiologies including metabolic, neoplastic, or active infectious origin.
   8. non-epileptic event/seizures

3. Adolescents currently on the ketogenic diet

4. Participation in a trial of an investigational drug or device within 30 days prior to screening

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Epilepsy Journey web-based modules alone	Epilepsy Journey web-based modules	Participants assigned to Epilepsy Journey modules will independently review web-based EJ modules. Participants will be targeted to complete 10 EJ modules (\~15-30 minutes each session) within 14 weeks.
Epilepsy Journey web-based modules + telehealth with a therapist	Epilepsy Journey web-based modules	Participants will receive both the Epilepsy Journey web-based modules and telehealth sessions with a therapist weekly. Participants will review 10 modules independently (\~15-30 minutes) and complete 10 telehealth sessions (\~30-45 minutes each session) within a 14-week time frame.
Epilepsy Journey web-based modules + telehealth with a therapist	Telehealth with a therapist	Participants will receive both the Epilepsy Journey web-based modules and telehealth sessions with a therapist weekly. Participants will review 10 modules independently (\~15-30 minutes) and complete 10 telehealth sessions (\~30-45 minutes each session) within a 14-week time frame.
Telehealth with a therapist alone	Telehealth with a therapist	Participants will meet with a therapist for 10 telehealth sessions (30-45 minutes each session) within a 14-week time frame.

Primary Outcome Measures

Name	Time	Method
Behavior Rating Inventory of Executive Function (2nd edition) Global Executive Composite T-score (parent)	26-weeks post-randomization	The parent-reported BRIEF-2 Global Executive Composite T-score will be used as the primary outcome measure. T-scores are linear transformations of raw scores, where 50 points represent the mean, and 10 points represent the standard deviation. T-scores provide information about an individual's score relative to a normal standardization sample, based on age and sex. T-scores ≥ 65 are considered clinically significant.

Secondary Outcome Measures

Name	Time	Method
PedsQL™ Epilepsy Module - Impact Subscale (Adolescent report)	26-weeks post-randomization	The PedsQL Epilepsy Module is reliable epilepsy-specific health-related quality of life (HRQOL) measure for youth 2-25 years with epilepsy. Five key domains will be assessed, including Impact, Cognitive Functioning, Executive Functioning, Sleep, and Mood/Behavior. Scores range from 0-100, with higher scores representing better HRQOL. Clinical cut-offs have been established for the measure, with scores below the cut-off representing concerning HRQOL: Impact \[Parent=60.7; Child=64.39\], Cognitive \[Parent=38.11; Child=50.97\], Executive Functioning \[Parent=46.65; Child=57.15\], Sleep \[Parent=42.07; Child=43.90\], and Mood/Behavior \[Parent=54.14; Child =53.30\].
PedsQL™ Epilepsy Module - Cognitive Functioning Subscale (Adolescent report)	26-weeks post-randomization	The PedsQL Epilepsy Module is reliable epilepsy-specific HRQOL measure for youth 2-25 years with epilepsy. Five key domains will be assessed, including Impact, Cognitive Functioning, Executive Functioning, Sleep, and Mood/Behavior. Scores range from 0-100, with higher scores representing better HRQOL. Clinical cut-offs have been established for the measure, with scores below the cut-off representing concerning HRQOL: Impact \[Parent=60.7; Child=64.39\], Cognitive \[Parent=38.11; Child=50.97\], Executive Functioning \[Parent=46.65; Child=57.15\], Sleep \[Parent=42.07; Child=43.90\], and Mood/Behavior \[Parent=54.14; Child =53.30\].
PedsQL™ Epilepsy Module - Executive Functioning Subscale (Adolescent report)	26-weeks post-randomization	The PedsQL Epilepsy Module is reliable epilepsy-specific HRQOL measure for youth 2-25 years with epilepsy. Five key domains will be assessed, including Impact, Cognitive Functioning, Executive Functioning, Sleep, and Mood/Behavior. Scores range from 0-100, with higher scores representing better HRQOL. Clinical cut-offs have been established for the measure, with scores below the cut-off representing concerning HRQOL: Impact \[Parent=60.7; Child=64.39\], Cognitive \[Parent=38.11; Child=50.97\], Executive Functioning \[Parent=46.65; Child=57.15\], Sleep \[Parent=42.07; Child=43.90\], and Mood/Behavior \[Parent=54.14; Child =53.30\].
PedsQL™ Epilepsy Module -Sleep Subscale (Adolescent report)	26-weeks post-randomization	The PedsQL Epilepsy Module is reliable epilepsy-specific HRQOL measure for youth 2-25 years with epilepsy. Five key domains will be assessed, including Impact, Cognitive Functioning, Executive Functioning, Sleep, and Mood/Behavior. Scores range from 0-100, with higher scores representing better HRQOL. Clinical cut-offs have been established for the measure, with scores below the cut-off representing concerning HRQOL: Impact \[Parent=60.7; Child=64.39\], Cognitive \[Parent=38.11; Child=50.97\], Executive Functioning \[Parent=46.65; Child=57.15\], Sleep \[Parent=42.07; Child=43.90\], and Mood/Behavior \[Parent=54.14; Child =53.30\].
PedsQL™ Epilepsy Module -Mood/Behavior Subscale (Adolescent report)	26-weeks post-randomization	The PedsQL Epilepsy Module is reliable epilepsy-specific HRQOL measure for youth 2-25 years with epilepsy. Five key domains will be assessed, including Impact, Cognitive Functioning, Executive Functioning, Sleep, and Mood/Behavior. Scores range from 0-100, with higher scores representing better HRQOL. Clinical cut-offs have been established for the measure, with scores below the cut-off representing concerning HRQOL: Impact \[Parent=60.7; Child=64.39\], Cognitive \[Parent=38.11; Child=50.97\], Executive Functioning \[Parent=46.65; Child=57.15\], Sleep \[Parent=42.07; Child=43.90\], and Mood/Behavior \[Parent=54.14; Child =53.30\].

Trial Locations

Locations (3)

Childrens Hospital of Orange County; 🇺🇸 Orange, California, United States

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States