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Surgery as a Treatment for Medically Intractable Epilepsy

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ClinicalTrials.gov Identifier: NCT01273129
Recruitment Status : Recruiting
First Posted : January 10, 2011
Last Update Posted : October 5, 2021
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

Tracking Information
First Submitted Date  ICMJE January 7, 2011
First Posted Date  ICMJE January 10, 2011
Last Update Posted Date October 5, 2021
Actual Study Start Date  ICMJE March 21, 2011
Estimated Primary Completion Date March 1, 2028   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 5, 2021)
Change in seizure frequency [ Time Frame: 1 year ]
Change in seizure frequency, as measured by the Engel scale before and 1 year after treatment.Engel s classification:Class I: patients who were completely seizure free, had auras only, or had convulsions with drug withdrawal only;Class II: rare disabling seizures or nocturnal seizures only;Class III: worthwhile improvement (frequent seizures but fewer than previously);Class IV: no improvement (frequent seizures with unchanged frequency compared to before surgery).The Engel Class rating will be made while the patient is taking antiepileptic medication
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 5, 2021)
  • Percentage of patients who are able to be completely withdrawn from anti-epileptic medication [ Time Frame: 2 Year ]
    The proportion of patients who are able to completely withdrawn from anti-epileptic medication (measured 2 years after surgery; subjects will remain on antiepileptic medications for one year after surgery, and may be withdrawn from antiepileptic medications during the second year after surgery).
  • Percentage of patients who are seizure-free (Engel Class I) [ Time Frame: 1 Year ]
    The proportion of patients who are seizure-free (Engel Class I) one year after surgery.
  • Mean Engel Class one year after surgery stratified by the type of surgical procedure [ Time Frame: 1 Year ]
    Mean Engel Class one year after surgery stratified by type of surgical procedure performed.
  • Percentage of patients with permanent neurological side effectsfrom surgical treatment [ Time Frame: 1 Year ]
    Permanent neurological deficits, assessed one year after surgery.
  • Neurophysiological correlates of cognitive function [ Time Frame: Baseline ]
    1. Differences in local field potential (LFP) oscillatory power in both intracranial EEG and microwire recordings among a) the awake resting state, b) during cognitive activity, c) immediately prior to and during seizure activity, and d) during sleep.2. Differences in measures of coherence and phase synchrony for LFP oscillations recorded from both intracranial EEG and microwire recordings amonga) the awake resting state,b) during cognitive activity,c) immediately prior to and during seizure activity, andd) during sleep.3. Differences in the event-related potential (ERP) recorded from both intracranial EEG and microwire recordings amonga) the awake resting state,b) during cognitive activity,c) immediately prior to and during seizure activity, andd) during sleep.4. Analysis of waveforms from individual microwires to identify action potentials reflective of single-unit activity and differences in firing rates for individual neurons
  • 6. Neurophysiological correlates of human cognitive function and to provide invasive monitoring for patients with tumor related epilepsy [ Time Frame: Baseline and 1 year ]
    Outcomes for subjects with tumor related epilepsy will be assessed under a separate protocol, 16-N-0041, Tumor Related Epilepsy
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Surgery as a Treatment for Medically Intractable Epilepsy
Official Title  ICMJE Surgery as a Treatment for Medically Intractable Epilepsy
Brief Summary

Background:

- Medically intractable epilepsy is the term used to describe epilepsy that cannot be controlled by medication. Many people whose seizures do not respond to medication will respond to surgical treatment, relieving seizures completely or almost completely in one-half to two-thirds of patients who qualify for surgery. The tests and surgery performed as part of this treatment are not experimental, but researchers are interested in training more neurologists and neurosurgeons in epilepsy surgery and care in order to better understand epilepsy and its treatment.

Objectives:

- To use surgery as a treatment for medically intractable epilepsy in children and adults.

Eligibility:

- Children and adults at least 8 years of age who have simple or complex partial seizures (seizures that come from one area of the brain) that have not responded to medication, and who are willing to have brain surgery to treat their medically intractable epilepsy.

Design:

  • Participants will be screened with a medical history, physical examination, and neurological examination. Imaging studies, including magnetic resonance imaging and computer-assisted tomography (CT), may also be conducted as part of the screening. Participants who do not need surgery or whose epilepsy cannot be treated surgically will follow up with a primary care physician or neurologist and will not need to return to the National Institutes of Health for this study.
  • Prior to the surgery, participants will have the following procedures to provide information on the correct surgical approach.
  • Video electroencephalography monitoring to measure brain activity during normal activities within a 24-hour period. Three to four 15-minute breaks are allowed within this period.
  • Wada test to evaluate speech, comprehension, and memory centers of the brain, using a contrast dye to study the blood vessels of the brain and a short-term anesthetic administration procedure to test the effects on areas of speech and memory.
  • Depth electrodes and/or brain surface electrodes to measure brain activities and determine the part of the brain that is responsible for the seizures (seizure focus).
  • Participants will have a surgical procedure at the site of their seizure focus. Brain lesions, abnormal blood vessels, tumors, infections, or other areas of brain abnormality will be either removed or treated in a way that will stop or help prevent the spread of seizures without affecting irreplaceable brain functions, such as the ability to speak, understand, move, feel, or see.
  • Participants will return for outpatient visits and brain imaging studies 2 months, 1 year, and 2 years after surgery.
Detailed Description

Objective

This protocol is being performed collect prospective data on patients who receive standard care therapy for drug resistant epilepsy and to follow the therapeutic course of patients from pre-operative evaluation, through surgery, and post-operatively, and to collect prospective data on seizure outcomes following surgery to add to the body of knowledge in this field. Primary outcome measures will be used to assess efficacy of

surgery for clinical care purposes. Any treatment under this protocol will be based on the current standard of care for epilepsy surgery. The secondary goals of this protocol will be to investigate neurophysiological correlates of human cognitive function and to provide invasive monitoring for patients with tumor related epilepsy.

Study Population

Patients 8 years and older whose seizures are uncontrollable with medication may participate in this study as well as patients with tumor related epilepsy in whom invasive monitoring is indicated.

Study Design

Patients will be screened by study neurologists to confirm their diagnosis of drug resistant epilepsy. Patients that do not have a confirmed diagnosis of drug resistant epilepsy will be offered further evaluation in protocol 18-N-0066, Investigating Epilepsy: Screening,Evaluation and Treatment. Patients confirmed to have drug resistant epilepsy will be offered standard invasive and non-invasive diagnostic and surgical procedures. Diagnostic invasive monitoring with intracranial electrodes for further localization of their seizure focus may be required. The ultimate goal is to surgically remove or modify the epileptic focus. Standard procedures to be performed are 1) anterior temporal lobectomy or 2) amygdalohippocampectomy for temporal lobe epilepsy, 3) focal cortical resection for epilepsy that arises outside the temporal lobe, 4) removal of brain lesions causing epilepsy, and 5) multiple subpial transection.

In patients in whom invasive monitoring is medically necessary, neurophysiologic activity during cognitive tasks will be captured from intracranial surface and depth electrodes. Analysis will focus on the role of neuronal firing and aggregate neural activity 1) during cognitive function, 2) in other states such as wakefulness and sleep, and 3) during periods of time surrounding seizure activity.

Drug Resistant Epilepsy

Patients with drug resistant epilepsy will be followed for two years after the surgical procedure and will receive standard neurological examinations and MRI evaluation of the brain. Patients who do not have surgical resection of epileptogenic tissue will complete participation after the three-month post-op visit. Participants in this protocol will be evaluated for potential eligibility for other NINDS clinical trials.

Tumor Related epilepsy

Patients with tumor related epilepsy will be enrolled in this protocol because of clinical indications arising from participation in a seperate protocol, 16-N-0041 Tumor Related Epilepsy. Patients will complete participation after the three-month post-op visit.

Outcome Measures

The primary goal of this protocol is to collect prospective data on patients who receive standard care therapy for drug resistant epilepsy, and to determine the efficacy of surgery for treatment while collecting physiology, tissue, and behavioral data for research.The primary outcome measure for patients with drug resistant epilepsy is the change in seizure frequency, as measured by the Engel scale before and 1 year after treatment. Secondary outcome measures include 1) percentage of patients who are able to be completely withdrawn from anti-epileptic medication; 2) percentage of patients who are seizure-free (Engel Class I); 3) mean Engel Class one year after surgery stratified by the type of surgical procedure; 4) percentage of patients with permanent neurological side-effects from surgical treatment; and 5) neurophysiological correlates of cognitive function. Outcomes for patients with tumor related epilepsy will be assessed under a seperate protocol, 16-N-0041, Tumor Related Epilepsy.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Epilepsy
  • Epilepsy, Temporal Lobe
  • Partial Epilepsy
Intervention  ICMJE Procedure: Surgical Treatment of drug resistantepilepsy

Removal of mesial temporal sclerosis through anterior temporal lobectomy or selective amygdalohippocamp ectomy. Selective amygdalohippocamp ectomy removes the medial temporal lobe and leaves more of the surrounding normal brain than anterior temporal lobectomy.

A non-ablative surgical, vagus nerve stimulation, uses electrodes implanted within the left carotid sheath, is an example of neuromodulation being used to treat drug resistant seizures.

Study Arms  ICMJE Experimental: 1
Patients 8 years of age or older with drug resistant epilepsy or tumor related epilepsy
Intervention: Procedure: Surgical Treatment of drug resistantepilepsy
Publications * Chittajallu R, Auville K, Mahadevan V, Lai M, Hunt S, Calvigioni D, Pelkey KA, Zaghloul KA, McBain CJ. Activity-dependent tuning of intrinsic excitability in mouse and human neurogliaform cells. Elife. 2020 Jun 4;9. pii: e57571. doi: 10.7554/eLife.57571.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 11, 2018)
300
Original Estimated Enrollment  ICMJE
 (submitted: January 7, 2011)
100
Estimated Study Completion Date  ICMJE March 1, 2028
Estimated Primary Completion Date March 1, 2028   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • INCLUSION CRITERIA:

To be eligible for entry into the study, candidates must meet all the following criteria:

  1. Be 8 years of age or older with drug resistant epilepsy or tumor related epilepsy.
  2. Have focal onset seizures.
  3. Seizures must persist despite medical therapy (drug resistant epilepsy) or seizures must be associated with the presence of a brain tumor.
  4. Able to give informed consent, or have a parent able to provide informed consent if a child.
  5. Agree to undergo brain surgery if indicated to treat drug resistant epilepsy.

EXCLUSION CRITERIA:

Candidates will be excluded if they:

  1. Are pregnant (subjects of childbearing age will be tested with a urine pregnancy test and will have agreed to avoid being pregnant by practicing a reliable form of contraception or by abstinence from sexual intercourse while undergoing evaluation for epilepsy surgery and for 1 month after epilepsy surgery).
  2. Cannot have an MRI scan.
  3. Have a bleeding disorder that cannot be corrected before invasive testing or surgery, or other medical conditions which would make testing or surgery unsafe, such as lung or cardiac disease which would increase the risk of general anesthesia or severe immunodeficiency or systemic cancer not related to a brain lesion.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 8 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Gretchen C Scott, R.N. Not Listed SNBrecruiting@nih.gov
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01273129
Other Study ID Numbers  ICMJE 110051
11-N-0051
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
Study Sponsor  ICMJE National Institute of Neurological Disorders and Stroke (NINDS)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Kareem A Zaghloul, M.D. National Institute of Neurological Disorders and Stroke (NINDS)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date January 4, 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP