Clinical trial NCT03441867: Neuroimaging Biomarker for Seizures
Official title: Neuroimaging Biomarker for Seizures
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
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
Lead sponsor: Providence VA Medical Center
Sponsor class: FED
Collaborators: name: University of Alabama at Birmingham
name: Rhode Island Hospital
name: Birmingham, Alabama VA Medical Center
name: United States Department of Defense
name: Ocean State Research Institute, Inc.
name: Brown University
First posted: 2018-02-22
Enrollment: 224
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Number of Epileptic Seizures
timeFrame: Baseline, Weeks 1,2,3,4,5,6,7,8,9,10,11,12, 8 months post baseline, 12 months post baseline
measure: Number of Nonepileptic Seizures (NES)
timeFrame: Baseline, Weeks 1,2,3,4,5,6,7,8,9,10,11,12, 8 months post baseline, 12 months post baseline
measure: Structural and Functional Neuroimaging
timeFrame: Baseline and week 13
Secondary outcomes:
measure: Beck Depression Inventory-II (BDI-II)
timeFrame: Baseline, Weeks 1,2,3,4,5,6,7,8,9,10,11,12, 8 months post baseline, 12 months post baseline
measure: Beck Anxiety Inventory (BAI)
timeFrame: Baseline, Weeks 6 and 10, 8 months post baseline, 12 months post baseline
measure: Quality of Life in Epilepsy-31 (QOLIE-31)
timeFrame: Baseline, Weeks 6 and 10
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Providence
country: United States
facility: Providence VA Medical Center
state: Rhode Island
Study officials:
affiliation: Providence VA Medical Center
name: W. Curt LaFrance, Jr., MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alabama at Birmingham
name: Jerzy Szarflarski, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.