CClinicalTrials.gg
Status unknownNCT03441867NIBMSZSUpdated Apr 5, 2022

Neuroimaging Biomarker for Seizures

An interventional study of Cognitive Behavioral Therapy for Seizures and Standard Medical Care in Seizure Disorder, Seizure Disorder, Post Traumatic and Traumatic Brain Injury, sponsored by Providence VA Medical Center. Status unknown at 3 sites in United States. Open to participants aged 18 Years to 60 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2022-04-05.

Sponsored by Providence VA Medical Center · Not applicable, Interventional, and Treatment

The sponsor has not verified this record recently (last verified Apr 2022), so the status shown — last known as Active, not recruiting — may be out of date.
Phase
Not applicable
Study type
Interventional
Enrollment
224
Allocation
Non-randomized
Ages
18 Years to 60 Years
Sex
All
01

Study 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.

Read the 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).

02

Conditions studied

  • Seizure Disorder
  • Seizure Disorder, Post Traumatic
  • Traumatic Brain Injury
  • Non-Epileptic Seizure
  • Conversion Disorder
  • Magnetic Resonance Imaging
  • Head Injury
  • Epilepsy

Keywords

  • Cognitive Behavioral Therapy
  • Veterans
  • Quality of Life
  • Stress Disorders, Post-Traumatic
  • Convulsion, Non-Epileptic
  • civilians
  • healthy volunteers
03

Who can participate

Ages eligible
18 Years to 60 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Eligibility 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), 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.
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
224 participants (actual)

Study arms

  • 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

  • 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

  • Active comparator
    TBI Control

    Participants with TBI will complete 2 brain fMRI scans.

    Other: Standard Medical Care

  • Active comparator
    Healthy Volunteer

    Healthy control volunteers will complete 2 brain fMRI scans.

    Other: Standard Medical Care

Interventions

  • BehavioralCognitive Behavioral Therapy for Seizures

    CBT-informed psychotherapy for patients with PNES and PTE

    Also known as: Cognitive Behavioral Therapy (CBT-Sz), (CBT-Sz) - PNES, (CBT-Sz) - PTE

  • OtherStandard Medical Care

    Observational - standard medical care

    Also known as: Treatment as Usual

05

What researchers measure

Primary outcomes

  1. Number of Epileptic Seizures

    epileptic seizure frequency (ES), collected prospectively, using a daily seizure calendar

    Time frame: Baseline, Weeks 1,2,3,4,5,6,7,8,9,10,11,12, 8 months post baseline, 12 months post baseline

  2. Number of Nonepileptic Seizures (NES)

    psychogenic nonepileptic seizure (NES) frequency, collected prospectively, using a daily seizure calendar

    Time frame: Baseline, Weeks 1,2,3,4,5,6,7,8,9,10,11,12, 8 months post baseline, 12 months post baseline

  3. Structural and Functional Neuroimaging

    Brain MRI scans

    Time frame: Baseline and week 13

Secondary outcomes

  1. Beck Depression Inventory-II (BDI-II)

    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.

    Time frame: Baseline, Weeks 1,2,3,4,5,6,7,8,9,10,11,12, 8 months post baseline, 12 months post baseline

  2. Beck Anxiety Inventory (BAI)

    The BDI-II assesses anxiety severity from "0" (no Anxiety-related symptom) to "3" (severe) on each question.

    Time frame: Baseline, Weeks 6 and 10, 8 months post baseline, 12 months post baseline

  3. Quality of Life in Epilepsy-31 (QOLIE-31)

    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.

    Time frame: Baseline, Weeks 6 and 10

06

Study locations

3 sites
  • University of Alabama at Birmingham
    Birmingham, Alabama 35294, United States
  • Rhode Island Hospital
    Providence, Rhode Island 02903, United States
  • Providence VA Medical Center
    Providence, Rhode Island 02908, United States
07

References and documents

Publications

  • LaFrance WC Jr, Baird GL, Barry JJ, Blum AS, Frank Webb A, Keitner GI, Machan JT, Miller I, Szaflarski JP; NES Treatment Trial (NEST-T) Consortium. Multicenter pilot treatment trial for psychogenic nonepileptic seizures: a randomized clinical trial. JAMA Psychiatry. 2014 Sep;71(9):997-1005. doi: 10.1001/jamapsychiatry.2014.817. PubMed 24989152 ↗
  • Salinsky M, Spencer D, Boudreau E, Ferguson F. Psychogenic nonepileptic seizures in US veterans. Neurology. 2011 Sep 6;77(10):945-50. doi: 10.1212/WNL.0b013e31822cfc46. PubMed 21893668 ↗
  • LaFrance WC Jr, Friedman JH. Cognitive behavioral therapy for psychogenic movement disorder. Mov Disord. 2009 Sep 15;24(12):1856-7. doi: 10.1002/mds.22683. No abstract available. Erratum In: Mov Disord. 2010 Oct 15;25(13):2268. PubMed 19562779 ↗
  • LaFrance WC Jr, Keitner GI, Papandonatos GD, Blum AS, Machan JT, Ryan CE, Miller IW. Pilot pharmacologic randomized controlled trial for psychogenic nonepileptic seizures. Neurology. 2010 Sep 28;75(13):1166-73. doi: 10.1212/WNL.0b013e3181f4d5a9. Epub 2010 Aug 25. PubMed 20739647 ↗
  • Reiter JM, Andrews DJ. A neurobehavioral approach for treatment of complex partial epilepsy: efficacy. Seizure. 2000 Apr;9(3):198-203. doi: 10.1053/seiz.1999.0374. PubMed 10775516 ↗
  • Elsas SM, Gregory WL, White G, Navarro G, Salinsky MC, Andrews DJ. Aura interruption: the Andrews/Reiter behavioral intervention may reduce seizures and improve quality of life - a pilot trial. Epilepsy Behav. 2011 Dec;22(4):765-72. doi: 10.1016/j.yebeh.2011.09.030. Epub 2011 Nov 6. PubMed 22056814 ↗
  • Michaelis R, Schonfeld W, Elsas SM. Trigger self-control and seizure arrest in the Andrews/Reiter behavioral approach to epilepsy: a retrospective analysis of seizure frequency. Epilepsy Behav. 2012 Mar;23(3):266-71. doi: 10.1016/j.yebeh.2011.11.023. Epub 2012 Feb 15. PubMed 22341960 ↗
  • Allendorfer JB, Szaflarski JP. Physiologic and cortical response to acute psychosocial stress in left temporal lobe epilepsy: response to a biochemical evaluation. Epilepsy Behav. 2014 Dec;41:312-3. doi: 10.1016/j.yebeh.2014.08.018. Epub 2014 Oct 11. No abstract available. PubMed 25306199 ↗
  • Szaflarski JP, Ficker DM, Cahill WT, Privitera MD. Four-year incidence of psychogenic nonepileptic seizures in adults in hamilton county, OH. Neurology. 2000 Nov 28;55(10):1561-3. doi: 10.1212/wnl.55.10.1561. PubMed 11094115 ↗
  • LaFrance WC Jr, Syc S. Depression and symptoms affect quality of life in psychogenic nonepileptic seizures. Neurology. 2009 Aug 4;73(5):366-71. doi: 10.1212/WNL.0b013e3181b04c83. PubMed 19652140 ↗
  • Szaflarski JP, Hughes C, Szaflarski M, Ficker DM, Cahill WT, Li M, Privitera MD. Quality of life in psychogenic nonepileptic seizures. Epilepsia. 2003 Feb;44(2):236-42. doi: 10.1046/j.1528-1157.2003.35302.x. PubMed 12558580 ↗
  • Voon V, Brezing C, Gallea C, Ameli R, Roelofs K, LaFrance WC Jr, Hallett M. Emotional stimuli and motor conversion disorder. Brain. 2010 May;133(Pt 5):1526-36. doi: 10.1093/brain/awq054. Epub 2010 Apr 5. PubMed 20371508 ↗

Study documents

  • Protocol and statistical analysis plan · Nov 6, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03441867
Lead sponsor
Providence VA Medical Center
Collaborators
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
Responsible party
Sponsor
First posted
Feb 22, 2018
Start date
Sep 15, 2017
Primary completion
May 15, 2022 (estimated)
Completion
Sep 14, 2022 (estimated)
Last update
Apr 5, 2022

Study contacts

W. Curt LaFrance, Jr., MD, MPH
principal investigator · Providence VA Medical Center
Jerzy Szarflarski, MD
principal investigator · University of Alabama at Birmingham

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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