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Noninvasive Pre-surgical Evaluation of Patients With Focal Epilepsy and Establishment of a Normative Imaging Database

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ClinicalTrials.gov Identifier: NCT02107989
Recruitment Status : Recruiting
First Posted : April 9, 2014
Last Update Posted : November 13, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

Brief Summary:

Objectives:

The overall study objective is to compare the sensitivities and specificities of morphometric analysis techniques using structural MRI images based on pre- and postsurgical localization of epileptic foci in patients undergoing presurgical evaluation for medically refractory epilepsy. To carry out these analyses, we aim to establish an age-stratified normative imaging database using healthy volunteers. Additional objectives are to identify abnormal networks in these patients using resting state fMRI/EEG and MEG/EEG, and to use language and memory fMRI tasks to examine the effects of epileptogenic zones and surgery on cognitive function and the networks associated with these functions.

Study population:

300 adults and children (age 8-65) with uncontrolled focal epilepsy, and 200 age-stratified healthy volunteers.

Design: A retrospective and prospective natural history study. Research procedures for patients in this study include neuropsychological testing and 1-4 MRI sessions during presurgical evaluation and an additional 1-3 MRI sessions and neuropsychological testing approximately 12 months post-operatively. Research testing (such as research neuropsychological tests or MRI scanning sequences) will be done during a visit for clinical testing whenever possible, likely reducing the number of required visits. Patients will also have optional MEG and 7T structural imaging. Data will also be obtained from patients who have already undergone epilepsy surgery if they had procedures as outlined in the protocol and are willing to share the data. Healthy volunteers will receive a subset of the pre-operative procedures for patients, requiring at least 3 visits. In order to ensure adequate data acquisition, subjects may be re-scanned up to three times for the portions of the study in which they participated, possibly requiring additional visits.

Outcome measures:

The main outcomes will be establishment of normative values for morphometric analysis methods in age-stratified normal controls, and comparison of the sensitivity and specificity of these measures to pre- and postsurgical localization of the epileptogenic zone. Secondary outcome measures will include determination of the sensitivity and specificity of source localization using MEG/EEG and resting state fMRI/EEG, and to evaluate changes in activation during rest, as well as language and memory fMRI tasks in patients pre- and postsurgically, to examine the effects of epileptogenic zones and surgery on cognitive function and the networks underlying these functions.


Condition or disease Intervention/treatment Phase
Epilepsy Device: MRI Device: MEG Not Applicable

Detailed Description:

Objectives: The overall study objective is to compare the sensitivities and specificities of morphometric analysis techniques using structural MRI images based on pre- and postsurgical localization of epileptic foci in patients undergoing presurgical evaluation for medically refractory epilepsy. To carry out these analyses, we aim to establish an age-stratified normative imaging database using healthy volunteers. Additional objectives are to identify abnormal networks in these patients using resting state fMRI/EEG and MEG/EEG, and to use language and memory fMRI tasks to examine the effects of epileptogenic zones and surgery on cognitive function and the networks associated with these functions.

Study population: 300 adults and children (age 8-65) with uncontrolled focal epilepsy, and 200 age-stratified healthy volunteers.

Design: A retrospective and prospective natural history study. Research procedures for patients in this study include neuropsychological testing and 1-4 MRI sessions during presurgical evaluation and an additional 1-3 MRI sessions and neuropsychological testing approximately 12 months post-operatively. Research testing (such as research neuropsychological tests or MRI scanning sequences) will be done during a visit for clinical testing whenever possible, likely reducing the number of required visits. Patients will also have optional MEG and 7T structural imaging. Data will also be obtained from patients who have already undergone epilepsy surgery if they had procedures as outlined in the protocol and are willing to share the data. Healthy volunteers will receive a subset of the pre-operative procedures for patients, requiring at least 3 visits. In order to ensure adequate data acquisition, subjects may be re-scanned up to three times for the portions of the study in which they participated, possibly requiring additional visits.

Outcome measures:

The main outcomes will be establishment of normative values for morphometric analysis methods in age-stratified normal controls, and comparison of the sensitivity and specificity of these measures to pre- and postsurgical localization of the epileptogenic zone. Secondary outcome measures will include determination of the sensitivity and specificity of source localization using MEG/EEG and resting state fMRI/EEG, and to evaluate changes in activation during rest, as well as language and memory fMRI tasks in patients pre- and postsurgically, to examine the effects of epileptogenic zones and surgery on cognitive function and the networks underlying these functions.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 500 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Noninvasive Pre-surgical Evaluation of Patients With Focal Epilepsy and Establishment of a Normative Imaging Database
Actual Study Start Date : March 11, 2014
Estimated Primary Completion Date : March 30, 2026
Estimated Study Completion Date : March 30, 2026


Arm Intervention/treatment
Experimental: healthy volunteers
healthy volunteers will get diagnostic testing at time zero and year later
Device: MRI
MRI of the brain is routinely used to identify abnormal areas of cortex in patients with medically refractory epilepsy. MRI evaluations of brain may be performed at field strengths of 1.5 T, 3T, and/or 7T, under conditions designated by the FDA as constituting nonsignificant risk.

Experimental: patients
patients will get diagnostic testing pre and post-operatively
Device: MRI
MRI of the brain is routinely used to identify abnormal areas of cortex in patients with medically refractory epilepsy. MRI evaluations of brain may be performed at field strengths of 1.5 T, 3T, and/or 7T, under conditions designated by the FDA as constituting nonsignificant risk.

Device: MEG

MEG/EEG:

Magnetoencephalogra phy (MEG) is commonly used during epilepsy pre- surgical evaluations to help with localizing epileptic foci. MEG will be obtained as clinically indicated, usually in patients with unclear seizure focus localization who are undergoing presurgical evaluation, particularly when they have frequent interictal discharges on EEG. MEG records very small magnetic fields generated by the brain at rest, or in response to a task or to epileptic activity. Resting state MEG/EEG analysis will be used for research purposes only.





Primary Outcome Measures :
  1. Determine age-adjusted normative values for morphometric analysis methods in healthy volunteers to form an age-adjusted template [ Time Frame: 1 yr/ postoperatively ]
    This will include surface and volume-based measures derived from high resolution T1, T2, FLAIR, and diffusion MR images

  2. To determine the sensitivity and specificity of these methods or combinations of these methods for detecting structural abnormalities underlying epileptogenic zones in individual patients [ Time Frame: 1 yr/ postoperatively ]
    a.Initial analysis of sensitivity and specificity will be based on comparison with pre-operative seizure focus determination based on conventional radiological MRI interpretation and scalp video-EEG monitoring. b.Final analysis will compare the sensitivity and specificity of these measures as well as conventional radiological MRI interpretation with seizure focus localization based on intracranial EEG findings and/or resection localization resulting in one year of seizure freedom


Secondary Outcome Measures :
  1. Using data derived from normative database, localization of epileptic zone [ Time Frame: 1 yr/ postoperatively ]
    Determine normative values for resting-state fMRI/EEG analysis techniques (such as average connectedness, interhemispheric connectedness, connectivity patterns as described below) in the age-stratified control groups, and determine the sensitivity and specificity of each technique or combination of techniques for epileptogenic zone localization (as described in the primary outcome)

  2. Using data derived from normative database, localize using morphometric analysis [ Time Frame: 1 yr/ postoperatively ]
    Determine normative values for resting-state EEG/MEG analysis techniques in the age-stratified control groups, and determine the sensitivity and specificity of these techniques for epileptogenic zone localization (as described in the primary outcome)

  3. Using data derived from normative database, localization by conventional radiological visual interpretation [ Time Frame: 1 yr/ postoperatively ]
    Assess the ability of a fMRI memory paradigm (verbal and visual abstract memory paradigms) to lateralize memory function, and evaluate whether the laterality index is altered in epilepsy patients compared to controls, particularly in patients with impaired material-specific memory on neuropsychological testing

  4. Using data derived from normative database, determine sensitivity and specificity for each morphometric measure [ Time Frame: 1 yr/ postoperatively ]
    Evaluate whether resting-state fMRI networks, language or memory laterality indices, or neuropsychological measures are altered following epilepsy surgery, and whether neuroimaging changes are correlated with seizure outcome and/or changes in neuropsychological testing.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   8 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA FOR PATIENTS:
  • Age 8-65 years old
  • Evaluated or under evaluation for epilepsy surgery under protocol 18-N-0066,11-N-0051 or 16-N-0041
  • Documentation of focal epilepsy based on MRI, EEG and/or ictal semiology
  • Ability to give informed consent or have a legally authorized representative able to give consent (for adults without consent capacity) or parent/guardian able to provide informed consent (for a child).

INCLUSION CRITERIA FOR PATIENTS SOLELY CONTRIBUTING DATA:

  • Had epilepsy surgery with presurgical evaluation under 18-N-0066
  • Age 8-65 at the time of epilepsy surgery evaluation
  • Had a preoperative structural brain MRI of the type used in this protocol

INCLUSION CRITERIA FOR HEALTHY VOLUNTEERS:

  • Age 8-65 years old
  • Ability to give informed consent or have a parent/guardian able to provide informed consent if a child.
  • Ability to cooperate with MRI scanning without anesthesia

EXCLUSION CRITERIA FOR PATIENTS:

  • Contraindications to MRI or MEG studies (such as pacemakers, cochlear implants, shrapnel, permanent eyeliner)
  • Claustrophobia or anxiety disorders exacerbated by the MRI scanner
  • Pregnancy. All females of childbearing potential must have a negative pregnancy test prior to MRI scanning

EXCLUSION CRITERIA FOR PATIENTS SOLELY CONTRIBUTING DATA:

-Not able or willing to give consent or do not have an appropriate surrogate who can provide consent

EXCLUSION CRITERIA FOR HEALTHY VOLUNTEERS:

  • Contraindications to MRI or MEG studies (such as pacemakers, cochlear implants, shrapnel, permanent eyeliner)
  • Claustrophobia or anxiety disorders exacerbated by the MRI scanner
  • Significant medical conditions that may affect the central nervous system, such as psychiatric disorders (such as mood disorders, psychotic disorders, substance abuse or dependence), significant neurologic disorders (such as brain injury, neurodegenerative disorders, multiple sclerosis, stroke, movement disorders, epilepsy), or active systemic disease that may affect the central nervous system (such as uncontrolled hypertension, autoimmune disorders or other inflammatory disorders, neoplastic disease)
  • Use of centrally acting medications in the past 6 weeks, such as benzodiazepines, barbiturates, antidepressants, beta-blockers, and drugs for treating epilepsy or migraine
  • Pregnancy. All females of childbearing potential must have a negative pregnancy test prior to MRI scanning

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02107989


Contacts
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Contact: Aaliyah H Hamidullah-Thiam (301) 496-5121 aaliyah.hamidullahthiam@nih.gov
Contact: Sara K Inati, M.D. (301) 435-6269 inatisk@mail.nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
Sponsors and Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
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Principal Investigator: Sara K Inati, M.D. National Institute of Neurological Disorders and Stroke (NINDS)

Additional Information:
Publications:
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Responsible Party: National Institute of Neurological Disorders and Stroke (NINDS)
ClinicalTrials.gov Identifier: NCT02107989     History of Changes
Other Study ID Numbers: 140061
14-N-0061
First Posted: April 9, 2014    Key Record Dates
Last Update Posted: November 13, 2019
Last Verified: October 8, 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) ):
Epilepsy
MRI
fMRI
MEG
Additional relevant MeSH terms:
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Epilepsy
Epilepsies, Partial
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases