Neuroimaging Biomarker for Seizures

Epilepsy Clinical Trial

— NIBMSZS  

Official title:

Neuroimaging Biomarker for Seizures

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03441867
• Other study ID #: Award Number W81XWH-17-1-0619
• Status: Active, not recruiting
• Phase: N/A
• Start date: September 15, 2017
• Est. completion date: September 14, 2022

Study information

• Verified date: April 2022
• Source: Providence VA Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 224
• Est. completion date: September 14, 2022
• Est. primary completion date: May 15, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Conversion Disorder
• Craniocerebral Trauma
• Disease
• Dissociative Disorders
• Epilepsy
• Epilepsy, Post-Traumatic
• Head Injury
• Magnetic Resonance Imaging
• Non-Epileptic Seizure
• Seizure Disorder
• Seizure Disorder, Post Traumatic
• Seizures
• Traumatic Brain Injury
• Wounds and Injuries

Intervention

Behavioral:
• Cognitive Behavioral Therapy for Seizures
CBT-informed psychotherapy for patients with PNES and PTE

Other:
• Standard Medical Care
Observational - standard medical care

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Providence VA Medical Center	Providence	Rhode Island
United States	Rhode Island Hospital	Providence	Rhode Island

Sponsors (7)

Lead Sponsor	Collaborator
Providence VA Medical Center	Birmingham, Alabama VA Medical Center, Brown University, Ocean State Research Institute, Inc., Rhode Island Hospital, United States Department of Defense, University of Alabama at Birmingham

Country where clinical trial is conducted

United States, 

References & Publications (12)

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. — View 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. — View 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. — View 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. Erratum in: Mov Disord. 2010 Oct 15;25(13):2268. — View 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. — View 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. — View 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. — View Citation

Reiter JM, Andrews DJ. A neurobehavioral approach for treatment of complex partial epilepsy: efficacy. Seizure. 2000 Apr;9(3):198-203. — View 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. — View 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. — View 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. — View 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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Structural and Functional Neuroimaging	Brain MRI scans	Baseline and week 13
Secondary	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.	Baseline, Weeks 1,2,3,4,5,6,7,8,9,10,11,12, 8 months post baseline, 12 months post baseline
Secondary	Beck Anxiety Inventory (BAI)	The BDI-II assesses anxiety severity from "0" (no Anxiety-related symptom) to "3" (severe) on each question.	Baseline, Weeks 6 and 10, 8 months post baseline, 12 months post baseline
Secondary	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.	Baseline, Weeks 6 and 10