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Neuroimaging Biomarker for Seizures (NIBMSZS)

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ClinicalTrials.gov Identifier: NCT03441867
Recruitment Status : Recruiting
First Posted : February 22, 2018
Last Update Posted : March 20, 2018
Sponsor:
Collaborators:
University of Alabama at Birmingham
Rhode Island Hospital
VA Office of Research and Development
United States Department of Defense
Ocean State Research Institute, Inc.
Brown University
Information provided by (Responsible Party):
Providence VA Medical Center

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 Behavioral: Cognitive Behavioral Therapy for Seizures Other: Standard Medical Care Not Applicable

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 176 Veterans will be compared to 88 Veterans 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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 264 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 : September 15, 2017
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : August 31, 2021


Arm Intervention/treatment
Experimental: (CBT-Sz) - PNES
Participants with history of a head injury and confirmed PNES 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

Other: Standard Medical Care
Observational - standard medical care
Other Name: Treatment as Usual

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

Other: Standard Medical Care
Observational - standard medical care
Other Name: Treatment as Usual

Active Comparator: TBI Control
Participants with TBI will complete 2 brain fMRI scans.
Other: Standard Medical Care
Observational - standard medical care
Other Name: Treatment as Usual




Primary Outcome Measures :
  1. Number of Epileptic Seizures [ Time Frame: 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

  2. Number of Nonepileptic Seizures (NES) [ Time Frame: 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

  3. Structural and Functional Neuroimaging [ Time Frame: Baseline and week 13 ]
    Brain MRI scans


Secondary Outcome Measures :
  1. Beck Depression Inventory-II (BDI-II) [ Time Frame: 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.

  2. Beck Anxiety Inventory (BAI) [ Time Frame: 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 anxiety severity from "0" (no Anxiety-related symptom) to "3" (severe) on each question.

  3. Quality of Life in Epilepsy-31 (QOLIE-31) [ Time Frame: Baseline, Weeks 1,2,3,4,5,6,7,8,9,10,11,12 ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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), in past 3 months.
    • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03441867


Contacts
Contact: W. Curt LaFrance, Jr., MD, MPH 401-273-7100 ext 2441 william_lafrance_jr@brown.edu
Contact: Krista Tocco, BA 401-273-7100 ext 6229 Krista.Tocco@va.gov

Locations
United States, Alabama
University of Alabama, Birmingham Recruiting
Birmingham, Alabama, United States, 35487
Contact: Amber Martin, MPH    205-975-4219    ambermartin@uabmc.edu   
Principal Investigator: Jerzy Szaflarski, MD, PhD         
Sub-Investigator: Jane Allendorfer, PhD         
Sub-Investigator: Mark Bolding, PhD         
Sub-Investigator: Lawrence Ver Hoef, MD         
Sub-Investigator: Tyler Gaston, MD         
Sub-Investigator: Leslie Perry, MD         
United States, Rhode Island
Rhode Island Hospital Recruiting
Providence, Rhode Island, United States, 02903
Contact: Krista Tocco    401-273-7100 ext 6229    Krista.Tocco@va.gov   
Principal Investigator: Andrew Blum, MD         
Sub-Investigator: Jason Machan, PhD         
Providence VA Medical Center Recruiting
Providence, Rhode Island, United States, 02908
Contact: Krista Tocco    401-273-7100 ext 6229    Krista.Tocco@va.gov   
Principal Investigator: W. Curt LaFrance, Jr., MD, MPH         
Sub-Investigator: Noah Philip, MD         
Sub-Investigator: Stephen Correia, PhD         
Sponsors and Collaborators
Providence VA Medical Center
University of Alabama at Birmingham
Rhode Island Hospital
VA Office of Research and Development
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
  Study Documents (Full-Text)

Documents provided by Providence VA Medical Center:

Publications:

Responsible Party: Providence VA Medical Center
ClinicalTrials.gov Identifier: NCT03441867     History of Changes
Other Study ID Numbers: Award Number W81XWH-17-1-0619
First Posted: February 22, 2018    Key Record Dates
Last Update Posted: March 20, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Providence VA Medical Center:
Cognitive Behavioral Therapy
Veterans
Quality of Life
Stress Disorders, Post-Traumatic
Convulsion, Non-Epileptic
civilians

Additional relevant MeSH terms:
Disease
Brain Injuries
Brain Injuries, Traumatic
Seizures
Epilepsy
Conversion Disorder
Hysteria
Dissociative Disorders
Epilepsy, Post-Traumatic
Pathologic Processes
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Neurologic Manifestations
Signs and Symptoms
Somatoform Disorders
Mental Disorders
Histrionic Personality Disorder
Personality Disorders