ReACT for Nonepileptic Seizures

(ReACT Trial)

Overseen By Stephanie Mueller, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Alabama at Birmingham

Disqualifiers: Epilepsy, Intellectual disability, Mental illness, others

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

Compensation: Varies

Number of Visits: 18

Duration: 12 weeks

50 Participants Needed

Trial Summary

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 adult psychogenic non-epileptic seizures (PNES, episodes resembling epileptic seizures but with no correlated epileptiform activity). 19 years and older participants diagnosed with PNES who are treated at UAB FND clinic will engage in twelve sessions of ReACT. Participants will be randomly assigned to one of three conditions: no wait, 3-month waiting period, 6-month waiting period. 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 (PCS), pain tolerance (time with hand in water) and cortisol response. Target assessments occur 7 days before treatment and 7 days after the 12th treatment session. Participants randomized to the 3-month and 6-month waiting period will also complete these measures one additional time immediately before the beginning of their waiting period. Long term follow-up assessments will occur at 2 months, 6 months and 12 months after the 12th treatment session. PNES frequency will be measured from 30 days before to 12 months after treatment. Participants randomized to the 3-month or 6-month waiting period conditions will log weekly PNES episodes until the start of therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It might be best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment ReTraining and Control Therapy (ReACT) for nonepileptic seizures?

Research shows that psychological treatments, like cognitive behavioral therapy and group therapy, can help reduce the frequency of nonepileptic seizures and improve quality of life. These therapies focus on understanding and managing stress and emotions, which are key components in treating nonepileptic seizures. ^{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 focuses on retraining the brain's response to stress and controlling the psychological factors contributing to nonepileptic seizures, unlike traditional treatments that primarily involve psychotherapy or medication. This approach may offer a novel way to address the underlying psychological triggers of the condition. ^{2 3 4 6 7}

Research Team

Aaron Fobian, PhD

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

This trial is for adults diagnosed with psychogenic non-epileptic seizures (PNES), which look like epileptic seizures but aren't. Participants must be treated at the UAB FND clinic and willing to undergo twelve sessions of ReACT therapy, with some waiting up to 6 months before starting treatment.

Inclusion Criteria

I am 19 years old or older.

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

Exclusion Criteria

I have epilepsy.

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

I experience fewer than 4 psychogenic non-epileptic seizures (PNES) a month.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

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

1 week

1 visit (in-person)

Waiting Period

Participants are randomized to a waiting period of either 0, 3, or 6 months before starting therapy. During this time, they log weekly PNES episodes.

0-6 months

Treatment

Participants receive 12 sessions of Retraining and Control Therapy (ReACT) via telehealth. Therapy sessions focus on changing behaviors and thoughts related to PNES.

12 weeks

12 visits (virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up assessments occur at 7 days, 2 months, 6 months, and 12 months after the 12th treatment session.

12 months

4 visits (virtual)

Treatment Details

Interventions

• ReTraining and Control Therapy (ReACT)

Trial Overview The study tests if ReACT, a behavior and thought-changing intervention, can improve control over actions and reduce catastrophic symptom expectations in PNES patients. It involves tasks measuring sense of control and responses to simulated stress (holding hand in cool water).

Participant Groups

Group I: 3-month waiting period Active Control 1 Intervention

At the end of the baseline visit, participants will be randomized to receive Retraining and Control Therapy (ReACT) after a waiting period of 3 months.

Group II: No waiting period Active Control 1 Intervention

At the end of the baseline visit, participants will be randomized to receive Retraining and Control Therapy (ReACT) with no waiting period.

Group III: 6-month waiting period Active Control 1 Intervention

At the end of the baseline visit, participants will be randomized to receive Retraining and Control Therapy (ReACT) after a waiting period of 6 months.

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+

Findings from Research

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]

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]

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]

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]

Psychogenic nonepileptic seizures (PNES) are classified as a conversion disorder and require interdisciplinary management that focuses on modifiable risk factors, with patient engagement being a critical but challenging first step.

Cognitive-behavioral therapy has shown promise in treating PNES, and a preliminary study of mindfulness-based psychotherapy in 6 patients suggests it is feasible and should be explored further in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of psychogenic nonepileptic seizures: updated review and findings from a mindfulness-based intervention case series. Baslet, G., Dworetzky, B., Perez, DL., et al.[2018]

In a study of 137 patients with various genetic epilepsies, perampanel showed a high responder rate of 71%, with an average seizure frequency reduction of 56.61%, indicating its efficacy as a treatment option.

Particularly effective in patients with specific genetic mutations like SCN1A and GNAO1, perampanel achieved over 90% seizure reduction in 27.5% of participants, suggesting a targeted mechanism of action related to glutamate transmission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perampanel as precision therapy in rare genetic epilepsies. Nissenkorn, A., Kluger, G., Schubert-Bast, S., et al.[2023]

References

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

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

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

Nonepileptic Seizures. [2020]

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

Treatment of psychogenic nonepileptic seizures: updated review and findings from a mindfulness-based intervention case series. [2018]

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

Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy A randomized trial. [2022]

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

Perampanel as precision therapy in rare genetic epilepsies. [2023]