ReACT for Nonepileptic Seizures

(ReACT Trial)

Overseen By Aaron Fobian, PhD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Alabama at Birmingham

Disqualifiers: Epilepsy, Other paroxysmal events, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

Duration: 12 weeks

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new ways to help children ages 11-18 with psychogenic non-epileptic seizures (PNES), which resemble seizures but aren't caused by electrical issues in the brain. Participants will try either Retraining and Control Therapy (ReACT) or supportive therapy to determine which better manages their symptoms and sense of control. The trial seeks children diagnosed with PNES by a doctor who experience at least four episodes a month. Participants will also complete tests to measure pain tolerance and stress response. This research aims to find better ways to support children dealing with these challenging episodes. As an unphased trial, it offers a unique opportunity to contribute to groundbreaking research that could improve support for kids with PNES.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it does exclude participants with certain conditions and those participating in other therapy during the study.

What prior data suggests that ReACT and supportive therapy are safe for treating pediatric psychogenic non-epileptic seizures?

Research shows that Retraining and Control Therapy (ReACT) has been used in both children and adults with psychogenic non-epileptic seizures (PNES). Studies have not reported any harmful effects or serious safety concerns, indicating that ReACT is well-tolerated. This therapy helps people change their thoughts and behaviors, which is generally considered safe.

Supportive Therapy, another treatment in this study, is also commonly used for PNES. It involves talking with a therapist to help manage symptoms and is generally safe. Research has not reported any negative effects from this type of therapy.

Both ReACT and Supportive Therapy have been studied in people with PNES, and neither treatment has shown significant safety issues in past research. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike standard treatments for nonepileptic seizures, which often focus on medication or traditional therapy, ReACT (Retraining and Control Therapy) offers a novel approach by aiming to retrain the brain's response to stressors that may trigger these seizures. Researchers are excited about ReACT because it provides a non-pharmacological option, potentially minimizing side effects associated with medication. Moreover, ReACT emphasizes empowering patients through active participation in their own treatment, which can lead to more sustainable long-term outcomes.

What evidence suggests that this trial's treatments could be effective for pediatric psychogenic non-epileptic seizures?

Research has shown that Retraining and Control Therapy (ReACT), which participants in this trial may receive, effectively treats children with psychogenic non-epileptic seizures (PNES). One study found that ReACT significantly reduced seizures, with all patients becoming seizure-free within seven days after treatment. This therapy helps patients change their thoughts and feelings about their symptoms, focusing on gaining control over them. Supportive therapy, another treatment option in this trial, also has evidence indicating it can help reduce seizure frequency. In some cases, half of the patients experienced a 50% or more reduction in seizures. Both therapies are promising, but ReACT has particularly strong support for its effectiveness. ^{1 2 6 7 8}

Who Is on the Research Team?

Aaron Fobian, PhD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for young people aged 11-18 with a diagnosis of psychogenic non-epileptic seizures (PNES), confirmed by video-EEG. They must experience at least four PNES per month and have a family member willing to participate. Those with comorbid epilepsy, other nonepileptic events, severe intellectual disability or mental illness, or those in another therapy are excluded.

Inclusion Criteria

A family member or guardian agrees to join the study with me.

My seizures have been diagnosed as non-epileptic by a doctor using video-EEG.

Exclusion Criteria

I experience sudden episodes not caused by epilepsy, such as those related to sleep issues or migraines.

Participation in other therapy during the study

I have epilepsy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Participants and their parent complete several questionnaires assessing demographics, mood, suicidality, relationships, and PNES symptoms. Saliva samples are collected, and sleep and PNES episode severity are tracked.

1 week

1 visit (in-person)

Treatment

Participants undergo 12 sessions of either ReACT or supportive therapy. The first session is in-person, and the remaining 11 sessions are conducted via telehealth.

12 weeks

1 visit (in-person), 11 visits (virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 7 days, 2 months, 6 months, and 12 months post-treatment.

12 months

4 visits (2 in-person, 2 virtual)

Open-label extension (optional)

Participants may opt into receiving the alternative therapy they were not randomized to after the 2-month follow-up.

What Are the Treatments Tested in This Trial?

Interventions

• ReACT
• Supportive Therapy

Trial Overview

The study compares Retraining and Control Therapy (ReACT) against supportive therapy in managing PNES. Participants will undergo twelve sessions of their assigned treatment. The effectiveness is measured through sense of control tasks, pain tolerance tests like the cold pressor test, and stress responses before and after treatment as well as six months later.

How Is the Trial Designed?

Group I: ReACT Intervention Experimental Treatment 1 Intervention

At the end of the baseline visit, half of the participants will be randomized to receive Retraining and Control Therapy (ReACT)

Group II: Healthy Control Active Control 1 Intervention

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.

Group III: Supportive Therapy Active Control 1 Intervention

At the end of the baseline visit, half of the participants will be randomized to receive supportive therapy

ReACT is already approved in United States for the following indications:

Approved in United States as ReACT for:

• Pediatric functional seizures

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

Cognitive behavioral therapy (CBT) has shown efficacy in treating psychogenic nonepileptic seizures (PNES), with evidence from a pilot randomized controlled trial indicating it is more effective than standard medical care.

While the antidepressant sertraline did not significantly reduce seizure frequency compared to placebo, it did lead to a notable decrease in symptoms from pre- to post-treatment, suggesting potential benefits that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychogenic nonepileptic seizures: a treatment review. What have we learned since the beginning of the millennium? Baslet, G.[2021]

In a study of 147 patients with psychogenic nonepileptic seizures (PNESs) followed for an average of 4.2 years, 28.6% achieved seizure remission, but nearly half of those remained unproductive, indicating that seizure control alone does not guarantee overall well-being.

Patients who stopped having seizures still reported significant ongoing psychological issues, suggesting that treatment for PNESs should address both seizure management and mental health to improve overall outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measuring outcome in psychogenic nonepileptic seizures: how relevant is seizure remission? Reuber, M., Mitchell, AJ., Howlett, S., et al.[2019]

Psychogenic nonepileptic seizures can be challenging to diagnose and require interdisciplinary collaboration for effective treatment, particularly when patients have combined seizures that may be resistant to medication.

In a case study of a 34-year-old woman, a combination of antiepileptic medication and psychotherapeutic techniques led to significant seizure reduction over two years, with complete seizure freedom and improved social functioning after four years of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Use of psychotherapy in patients with combined epileptic and nonepileptic seizures]. Chmelarová, D.[2006]

This study highlights the challenges and methodologies involved in conducting treatment trials for psychological nonepileptic seizures (NES), noting that only six out of eight enrolled patients completed the trial, indicating potential issues with retention in future studies.

The authors emphasize the importance of comprehensive neuropsychiatric assessments and the use of various symptom scales to effectively monitor outcomes in randomized controlled trials for NES, which could improve the design of future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methodological issues in conducting treatment trials for psychological nonepileptic seizures. LaFrance, WC., Blum, AS., Miller, IW., et al.[2021]

A specialized clinic for treating nonepileptic seizures (NES) was established, combining neurology and psychiatry services, and successfully treated 106 patients with a high retention rate of 65.4% after referral and 84.0% adherence to group therapy.

The clinic model not only provided effective psychological care but also led to a decrease in healthcare utilization, indicating its potential to improve access to care for both NES and epilepsy patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The feasibility of a multidisciplinary group therapy clinic for the treatment of nonepileptic seizures. Libbon, R., Gadbaw, J., Watson, M., et al.[2020]

The primary treatment goal for nonepileptic seizures (NES) is to improve quality of life by reducing seizure frequency through a combination of education, mental health support, and gradual weaning off anticonvulsants.

With appropriate diagnosis and treatment, approximately 45% of NES patients can become seizure-free, and an additional one-third may experience a reduction in seizure frequency, highlighting the effectiveness of integrated psychiatric care alongside psychotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonepileptic Seizures. Bowman, ES.[2020]

In-session seizures are more common in patients with psychogenic nonepileptic seizures (PNES), occurring in 1 in 36 therapy sessions, compared to 1 in 136 sessions for patients with epilepsy, indicating a significantly higher risk for PNES patients (odds ratio 4.4).

Despite the occurrence of in-session seizures, they rarely disrupted therapy significantly and were typically managed effectively by therapists, suggesting that psychological treatments can be safely conducted with appropriate seizure management plans in place.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The frequency and management of seizures during psychological treatment among patients with psychogenic nonepileptic seizures and epilepsy. Kemp, S., Graham, CD., Chan, R., et al.[2018]

A study involving 14 children with functional seizures showed that one year after completing Retraining and Control Therapy (ReACT), the frequency of seizures significantly decreased from an average of 5.62 seizures per week to 0.15, indicating long-term effectiveness of the treatment.

Both children and their parents reported that ReACT was helpful, supporting the idea that directly targeting functional seizures is more effective than focusing on mood or stress-related factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One-year follow-up of treatment outcomes and patient opinions of Retraining and Control Therapy (ReACT) for pediatric functional seizures. Stager, L., Szaflarski, JP., Fobian, AD.[2022]

In a clinical trial with 21 outpatients diagnosed with psychogenic nonepileptic seizures (PNES), cognitive behavioral therapy (CBT) significantly reduced seizure frequency, with 11 out of 17 participants reporting no seizures by the end of treatment.

CBT also led to improvements in psychiatric symptoms, psychosocial functioning, and quality of life, indicating its effectiveness not just for seizure reduction but also for overall mental health and well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive behavioral therapy for psychogenic nonepileptic seizures. LaFrance, WC., Miller, IW., Ryan, CE., et al.[2018]

Citations

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Comorbid epilepsy was allowed if participants had no epileptic seizures for ≥6 months before starting ReACT. Exclusion criteria included substance abuse, ...