Neuroimaging Biomarker for Seizures

NCT ID: NCT03441867

Last Updated: 2022-04-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

224 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-09-15

Study Completion Date

2022-09-14

Brief Summary

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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.

Detailed Description

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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).

Conditions

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

The neuroimaging analysis will be masked.

Study Groups

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(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.

Group Type EXPERIMENTAL

Cognitive Behavioral Therapy for Seizures

Intervention Type BEHAVIORAL

CBT-informed psychotherapy for patients with PNES and PTE

(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.

Group Type EXPERIMENTAL

Cognitive Behavioral Therapy for Seizures

Intervention Type BEHAVIORAL

CBT-informed psychotherapy for patients with PNES and PTE

TBI Control

Participants with TBI will complete 2 brain fMRI scans.

Group Type ACTIVE_COMPARATOR

Standard Medical Care

Intervention Type OTHER

Observational - standard medical care

Healthy Volunteer

Healthy control volunteers will complete 2 brain fMRI scans.

Group Type ACTIVE_COMPARATOR

Standard Medical Care

Intervention Type OTHER

Observational - standard medical care

Interventions

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Cognitive Behavioral Therapy for Seizures

CBT-informed psychotherapy for patients with PNES and PTE

Intervention Type BEHAVIORAL

Standard Medical Care

Observational - standard medical care

Intervention Type OTHER

Other Intervention Names

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Cognitive Behavioral Therapy (CBT-Sz) (CBT-Sz) - PNES (CBT-Sz) - PTE Treatment as Usual

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Alabama at Birmingham

OTHER

Sponsor Role collaborator

Rhode Island Hospital

OTHER

Sponsor Role collaborator

Birmingham, Alabama VA Medical Center

FED

Sponsor Role collaborator

United States Department of Defense

FED

Sponsor Role collaborator

Ocean State Research Institute, Inc.

OTHER

Sponsor Role collaborator

Brown University

OTHER

Sponsor Role collaborator

Providence VA Medical Center

FED

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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W. Curt LaFrance, Jr., MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Providence VA Medical Center

Jerzy Szarflarski, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Providence VA Medical Center

Providence, Rhode Island, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 24989152 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21893668 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19562779 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20739647 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10775516 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22056814 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22341960 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25306199 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11094115 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19652140 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12558580 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20371508 (View on PubMed)

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. 2025 Sep 25. doi: 10.1002/jclp.70047. Online ahead of print.

Reference Type DERIVED
PMID: 40996372 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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Award Number W81XWH-17-1-0619

Identifier Type: -

Identifier Source: org_study_id

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