NIBMSZS: Neuroimaging Biomarker for Seizures

Sponsor

Providence VA Medical Center (U.S. Fed)

Overall Status

Active, not recruiting

CT.gov ID

NCT03441867

Collaborator

University of Alabama at Birmingham (Other), Rhode Island Hospital (Other), Birmingham, Alabama VA Medical Center (U.S. Fed), United States Department of Defense (U.S. Fed), Ocean State Research Institute, Inc. (Other), Brown University (Other)

224

Enrollment

Locations

Arms

Anticipated Duration (Months)

74.7

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This multi-site study will examine patients with epilepsy (ES) following head injury [i.e., posttraumatic epilepsy (PTE)] and posttraumatic psychogenic Non-epileptic seizures (PNES) and will compare them to patients with traumatic brain injury (TBI) who do not have seizures using functional neuroimaging.

Condition or Disease	Intervention/Treatment	Phase
Seizure Disorder Seizure Disorder, Post Traumatic Traumatic Brain Injury Non-Epileptic Seizure Conversion Disorder Magnetic Resonance Imaging Head Injury Epilepsy	Behavioral: Cognitive Behavioral Therapy for Seizures Other: Standard Medical Care	N/A

Detailed Description

Numerous Veterans and civilians have seizures, which can be epileptic or nonepileptic in nature. Epileptic seizures are caused by abnormal brain cell firing. Nonepileptic seizures appear similar to epileptic seizures, but are associated with traumatic experiences and underlying psychological stressors. Both types of seizure are common and disabling, and many patients with seizures do not have adequate control resulting in loss of quality of life.

In this proposed 3-site study ( Providence, RI and Birmingham, AL), which are epilepsy centers with expertise both in epilepsy and psychogenic nonepileptic seizures (PNES), we will enroll 88 patients with video-EEG confirmed PNES and 88 with confirmed post-traumatic epilepsy (PTE) and will obtain functional neuroimaging before and after they receive a behavioral treatment - Cognitive Behavioral Therapy for Seizures. The functional neuroimaging studies in these patients will be compared to patients with traumatic brain injury without seizures to test the hypothesis that the faulty processing of emotions and stress in patients with PNES/PTE and abnormal brain connectivity have unique signals in patients with seizures compared to Veterans without seizures and that the neuroimaging signatures can be modified using behavioral intervention.

Impact: This grant application for the first study investigating mechanisms of PNES and PTE will provide increased understanding of neural circuitry in PTE and PNES, which can inform PTE and PNES treatments and could change clinical neurologic and psychiatric practice for PTE and PNES.

Participants will be recruited at the Providence VA Medical Center, Rhode Island Hospital, and University of Alabama, Birmingham (UAB).

Study Design

Study Type:

Interventional

Actual Enrollment :

224 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Masking Description:

The neuroimaging analysis will be masked.

Primary Purpose:

Treatment

Official Title:

Neuroimaging Biomarker for Seizures

Actual Study Start Date :

Sep 15, 2017

Anticipated Primary Completion Date :

May 15, 2022

Anticipated Study Completion Date :

Sep 14, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: (CBT-Sz) - PNES Participants with history of a head injury and confirmed Psychogenic Non-Epileptic Seizures will complete 2 brain fMRI scans along with 12 weeks of one hour CBT-Sz sessions by a trained therapist.	Behavioral: Cognitive Behavioral Therapy for Seizures CBT-informed psychotherapy for patients with PNES and PTE Other Names: Cognitive Behavioral Therapy (CBT-Sz) (CBT-Sz) - PNES (CBT-Sz) - PTE
Experimental: (CBT-Sz) - PTE Participants with history of a head injury and confirmed Post-Traumatic Epilepsy (PTE) will complete 2 brain fMRI scans along with 12 weeks of one hour CBT-Sz sessions by a trained therapist.	Behavioral: Cognitive Behavioral Therapy for Seizures CBT-informed psychotherapy for patients with PNES and PTE Other Names: Cognitive Behavioral Therapy (CBT-Sz) (CBT-Sz) - PNES (CBT-Sz) - PTE
Active Comparator: TBI Control Participants with TBI will complete 2 brain fMRI scans.	Other: Standard Medical Care Observational - standard medical care Other Names: Treatment as Usual
Active Comparator: Healthy Volunteer Healthy control volunteers will complete 2 brain fMRI scans.	Other: Standard Medical Care Observational - standard medical care Other Names: Treatment as Usual

Outcome Measures

Primary Outcome Measures

Number of Epileptic Seizures [Baseline, Weeks 1,2,3,4,5,6,7,8,9,10,11,12, 8 months post baseline, 12 months post baseline]
epileptic seizure frequency (ES), collected prospectively, using a daily seizure calendar
Number of Nonepileptic Seizures (NES) [Baseline, Weeks 1,2,3,4,5,6,7,8,9,10,11,12, 8 months post baseline, 12 months post baseline]
psychogenic nonepileptic seizure (NES) frequency, collected prospectively, using a daily seizure calendar
Structural and Functional Neuroimaging [Baseline and week 13]
Brain MRI scans

Secondary Outcome Measures

Beck Depression Inventory-II (BDI-II) [Baseline, Weeks 1,2,3,4,5,6,7,8,9,10,11,12, 8 months post baseline, 12 months post baseline]
The BDI-II assesses depression severity from "0" (no Depression-related symptom) to "3" (severe) on each question. The highest possible score is "51", relating to the worst outcome.
Beck Anxiety Inventory (BAI) [Baseline, Weeks 6 and 10, 8 months post baseline, 12 months post baseline]
The BDI-II assesses anxiety severity from "0" (no Anxiety-related symptom) to "3" (severe) on each question.
Quality of Life in Epilepsy-31 (QOLIE-31) [Baseline, Weeks 6 and 10]
his is a 31-item self-report scale used in the seizure population to evaluate Quality of Life. The lowest possible score is 0 and the highest possible score is 100, reflecting a better quality of life.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Inclusion criteria for PNES, ES and TBI (w/o PNES or ES) participants
Individuals with history of documented TBI (any severity).
Males and Females ages 18-60 years .
Women of child bearing potential, if currently using appropriate contraception.

Inclusion criteria of PNES and ES participants.

Diagnosed by video/EEG with lone PNES or by EEG with lone ES.
Patients must have at least 1 PNES or 1 ES during the year prior to enrollment.

Exclusion Criteria:

Exclusion Criteria of PNES, ES and TBI (w/o PNES or ES) participants
Current or past year self-injurious behavior.
Current suicidal intent (BDI suicide question 9 score of >1).
Current or past year psychosis.
Pending litigation or current application for long term disability.
Active substance or alcohol use disorder (dependence), per discretion of the investigators.
Serious illness requiring systemic treatment or hospitalization; the participant either completes therapy or is clinically stable on therapy, for at least 30 days prior to study entry.
Inability to fill out the self-report surveys.
Women who are or/are attempting to become pregnant during the study.
Ineligible or unwilling to complete MRI imaging.
Inability to document TBI.

Exclusion Criteria for PNES and ES participants

Inability or unwillingness to participate in CBT and assigned homework.
Currently enrolled in cognitive therapy aimed at PNES (Current CBT or other psychotherapy may be administered).
Concurrent mixed ES/PNES or equivocal video/EEG findings in discerning between ES and PNES will not be enrolled.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Rhode Island Hospital	Providence	Rhode Island	United States	02903
3	Providence VA Medical Center	Providence	Rhode Island	United States	02908

Sponsors and Collaborators

Providence VA Medical Center
University of Alabama at Birmingham
Rhode Island Hospital
Birmingham, Alabama VA Medical Center
United States Department of Defense
Ocean State Research Institute, Inc.
Brown University

Investigators

Principal Investigator: W. Curt LaFrance, Jr., MD, MPH, Providence VA Medical Center
Principal Investigator: Jerzy Szarflarski, MD, University of Alabama at Birmingham