Neuroimaging Biomarker for Seizures

NCT03441867 | Unknown DMC

• 1 other identifier: Award Number W81XWH-17-1-0619
• Study Type: interventional
• Target: 224
• Locations: 1 country
• Sites: 3

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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• Number of Epileptic Seizures

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

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

• Number of Nonepileptic Seizures (NES)

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

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

• Structural and Functional Neuroimaging

  Brain MRI scans

  Baseline and week 13

Secondary Outcomes (3)

• 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

• Beck Anxiety Inventory (BAI)

  Baseline, Weeks 6 and 10, 8 months post baseline, 12 months post baseline

• Quality of Life in Epilepsy-31 (QOLIE-31)

  Baseline, Weeks 6 and 10

Study Arms (4)

(CBT-Sz) - PNES

EXPERIMENTAL

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-Sz) - PTE

EXPERIMENTAL

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

TBI Control

ACTIVE COMPARATOR

Participants with TBI will complete 2 brain fMRI scans.

Other: Standard Medical Care

Healthy Volunteer

ACTIVE COMPARATOR

Healthy control volunteers will complete 2 brain fMRI scans.

Other: Standard Medical Care

Interventions

Cognitive Behavioral Therapy for Seizures BEHAVIORAL

CBT-informed psychotherapy for patients with PNES and PTE

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

(CBT-Sz) - PNES; (CBT-Sz) - PTE

Standard Medical Care OTHER

Observational - standard medical care

Also known as: Treatment as Usual

Healthy Volunteer; TBI Control

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

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

Study Sites (3)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Providence VA Medical Center

Providence, Rhode Island, 02908, United States

Location

Related Publications (13)

• 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.

  PMID: 24989152 BACKGROUND

• 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.

  PMID: 21893668 BACKGROUND

• 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.

  PMID: 19562779 BACKGROUND

• 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.

  PMID: 20739647 BACKGROUND

• 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.

  PMID: 10775516 BACKGROUND

• 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.

  PMID: 22056814 BACKGROUND

• 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.

  PMID: 22341960 BACKGROUND

• 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.

  PMID: 25306199 BACKGROUND

• 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.

  PMID: 11094115 BACKGROUND

• 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.

  PMID: 19652140 BACKGROUND

• 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.

  PMID: 12558580 BACKGROUND

• 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.

  PMID: 20371508 BACKGROUND

• Van Patten R, Cotton E, Chan L, Altalib H, Tocco K, Gaston TE, Grayson LP, Martin A, Fry S, Goodman A, Allendorfer JB, Blum A, Szaflarski JP, LaFrance WC Jr. Neurobehavioral Therapy Is Associated With Improvements in Social Functioning in Patients With Functional Seizures and Traumatic Brain Injury. J Clin Psychol. 2026 Jan;82(1):84-96. doi: 10.1002/jclp.70047. Epub 2025 Sep 25.

  PMID: 40996372 DERIVED

MeSH Terms

Conditions

Epilepsy; Epilepsy, Post-Traumatic; Brain Injuries, Traumatic; Seizures; Conversion Disorder; Craniocerebral Trauma; Stress Disorders, Post-Traumatic

Interventions

Cognitive Behavioral Therapy; Therapeutics

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Injuries; Trauma, Nervous System; Wounds and Injuries; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Somatoform Disorders; Mental Disorders; Stress Disorders, Traumatic; Trauma and Stressor Related Disorders

Intervention Hierarchy (Ancestors)

Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Study Officials

• W. Curt LaFrance, Jr., MD, MPH

  Providence VA Medical Center

  PRINCIPAL INVESTIGATOR

• Jerzy Szarflarski, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: The neuroimaging analysis will be masked.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 29, 2017
• First Posted: February 22, 2018
• Study Start: September 15, 2017
• Primary Completion: May 15, 2022
• Study Completion: September 14, 2022
• Last Updated: April 5, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)