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Neuroimaging Biomarker for Seizures (NIBMSZS)

Primary Purpose

Seizure Disorder, Seizure Disorder, Post Traumatic, Traumatic Brain Injury

Status

Active

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Cognitive Behavioral Therapy for Seizures

Standard Medical Care

About this trial

This is an interventional treatment trial for Seizure Disorder focused on measuring Cognitive Behavioral Therapy, Veterans, Quality of Life, Stress Disorders, Post-Traumatic, Convulsion, Non-Epileptic, civilians, healthy volunteers

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

University of Alabama at Birmingham
Rhode Island Hospital
Providence VA Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Arm Label

(CBT-Sz) - PNES

(CBT-Sz) - PTE

TBI Control

Healthy Volunteer

Arm Description

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.

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.

Participants with TBI will complete 2 brain fMRI scans.

Healthy control volunteers will complete 2 brain fMRI scans.

Outcomes

Primary Outcome Measures

Number of Epileptic Seizures

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

Number of Nonepileptic Seizures (NES)

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

Structural and Functional Neuroimaging

Brain MRI scans

Secondary Outcome Measures

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.

Beck Anxiety Inventory (BAI)

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)

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.

Full Information

NCT ID

NCT03441867

First Posted

December 29, 2017

Last Updated

April 4, 2022

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

1. Study Identification

Unique Protocol Identification Number

NCT03441867

Brief Title

Neuroimaging Biomarker for Seizures

Acronym

NIBMSZS

Official Title

Neuroimaging Biomarker for Seizures

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

September 15, 2017 (Actual)

Primary Completion Date

May 15, 2022 (Anticipated)

Study Completion Date

September 14, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the 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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Masking Description

The neuroimaging analysis will be masked.

Allocation

Non-Randomized

Enrollment

224 (Actual)

8. Arms, Groups, and Interventions

Arm Title

(CBT-Sz) - PNES

Arm Type

Experimental

Arm Description

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.

Arm Title

(CBT-Sz) - PTE

Arm Type

Experimental

Arm Description

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.

Arm Title

TBI Control

Arm Type

Active Comparator

Arm Description

Participants with TBI will complete 2 brain fMRI scans.

Arm Title

Healthy Volunteer

Arm Type

Active Comparator

Arm Description

Healthy control volunteers will complete 2 brain fMRI scans.

Intervention Type

Behavioral

Intervention Name(s)

Cognitive Behavioral Therapy for Seizures

Other Intervention Name(s)

Cognitive Behavioral Therapy (CBT-Sz), (CBT-Sz) - PNES, (CBT-Sz) - PTE

Intervention Description

CBT-informed psychotherapy for patients with PNES and PTE

Intervention Type

Other

Intervention Name(s)

Standard Medical Care

Other Intervention Name(s)

Treatment as Usual

Intervention Description

Observational - standard medical care

Primary Outcome Measure Information:

Title

Number of Epileptic Seizures

Description

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

Title

Number of Nonepileptic Seizures (NES)

Description

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

Title

Structural and Functional Neuroimaging

Description

Brain MRI scans

Time Frame

Baseline and week 13

Secondary Outcome Measure Information:

Title

Beck Depression Inventory-II (BDI-II)

Description

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

Title

Beck Anxiety Inventory (BAI)

Description

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

Title

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

Description

Time Frame

Baseline, Weeks 6 and 10

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

W. Curt LaFrance, Jr., MD, MPH

Organizational Affiliation

Providence VA Medical Center

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Jerzy Szarflarski, MD

Organizational Affiliation

University of Alabama at Birmingham

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Alabama at Birmingham

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35294

Country

United States

Facility Name

Rhode Island Hospital

City

Providence

State/Province

Rhode Island

ZIP/Postal Code

02903

Country

United States

Facility Name

Providence VA Medical Center

City

Providence

State/Province

Rhode Island

ZIP/Postal Code

02908

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

24989152

Citation

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.

Results Reference

background

PubMed Identifier

21893668

Citation

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.

Results Reference

background

PubMed Identifier

19562779

Citation

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.

Results Reference

background

PubMed Identifier

20739647

Citation

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.

Results Reference

background

PubMed Identifier

10775516

Citation

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.

Results Reference

background

PubMed Identifier

22056814

Citation

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.

Results Reference

background

PubMed Identifier

22341960

Citation

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.

Results Reference

background

PubMed Identifier

25306199

Citation

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.

Results Reference

background

PubMed Identifier

11094115

Citation

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.

Results Reference

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PubMed Identifier

19652140

Citation

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.

Results Reference

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PubMed Identifier

12558580

Citation

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.

Results Reference

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PubMed Identifier

20371508

Citation

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.

Results Reference

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Neuroimaging Biomarker for Seizures

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