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?

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 2 months after the 12th treatment session. Long term follow-up assessments will occur 6 months and 12 months after the 12th treatment session. PNES frequency will be measured from 30 days before to 12 months after treatment.

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.

Is ReACT therapy safe for humans?

The available research on treatments similar to ReACT, such as group therapy and psychodynamic therapy for nonepileptic seizures, suggests these therapies are generally safe for humans. Psychological treatments have been shown to improve outcomes without significant safety concerns, although the risk of in-session seizures during therapy is noted. ^{1 2 3 4 5}

How is the ReACT treatment different from other treatments for nonepileptic seizures?

ReACT (Retraining and Control Therapy) is unique because it combines supportive psychotherapy with techniques to help patients retrain their responses to stress, aiming to reduce or stop nonepileptic seizures by addressing their psychological roots. Unlike standard treatments that may focus on medication, ReACT emphasizes psychological therapy and coping strategies to improve quality of life. ^{1 5 6 7 8}

What data supports the effectiveness of the treatment ReACT for nonepileptic seizures?

Research shows that Retraining and Control Therapy (ReACT) significantly reduces seizure frequency in children with functional seizures, with improvements maintained one year after treatment. Additionally, patients and their parents find ReACT beneficial, supporting its effectiveness. ^{1 4 5 6 9}

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

Participation in other therapy during the study

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

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

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]

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]

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]

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]

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]

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]

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

1. United States pubmed.ncbi.nlm.nih.gov

The feasibility of a multidisciplinary group therapy clinic for the treatment of nonepileptic seizures. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Nonepileptic Seizures. [2020]

3. United States 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. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

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

5. United States pubmed.ncbi.nlm.nih.gov

Measuring outcome in psychogenic nonepileptic seizures: how relevant is seizure remission? [2019]

6. United States pubmed.ncbi.nlm.nih.gov

The frequency and management of seizures during psychological treatment among patients with psychogenic nonepileptic seizures and epilepsy. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Methodological issues in conducting treatment trials for psychological nonepileptic seizures. [2021]

8. Czech Republic pubmed.ncbi.nlm.nih.gov

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

9. United States pubmed.ncbi.nlm.nih.gov

Cognitive behavioral therapy for psychogenic nonepileptic seizures. [2018]