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Use of a Tonometer to Identify Epileptogenic Lesions During Pediatric Epilepsy Surgery

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ClinicalTrials.gov Identifier: NCT04344626
Recruitment Status : Recruiting
First Posted : April 14, 2020
Last Update Posted : April 14, 2020
Sponsor:
Collaborator:
Université de Montréal
Information provided by (Responsible Party):
Aria Fallah, University of California, Los Angeles

Brief Summary:

Refractory epilepsy, meaning epilepsy that no longer responds to medication, is a common neurosurgical indication in children. In such cases, surgery is the treatment of choice. Complete resection of affected brain tissue is associated with highest probability of seizure freedom. However, epileptogenic brain tissue is visually identical to normal brain tissue, complicating complete resection. Modern investigative methods are of limited use.

An important subjective assessment during surgery is that affected brain tissue feels stiffer, however there is presently no way to determine this without committing to resecting the affected area. It is hypothesized that intra-operative use of a tonometer (Diaton) will identify abnormal brain tissue stiffness in affected brain relative to normal brain. This will help identify stiffer brain regions without having to resect them.

The objective is to determine if intra-operative use of a tonometer to measure brain tissue stiffness will offer additional precision in identifying epileptogenic lesions.

In participants with refractory epilepsy, various locations on the cerebral cortex will be identified using standard pre-operative investigations like magnetic resonance imagin (MRI) and positron emission tomography (PET). These are areas of presumed normal and abnormal brain where the tonometer will be used during surgery to measure brain tissue stiffness. Brain tissue stiffness measurements will then be compared with results of routine pre-operative and intra-operative tests. Such comparisons will help determine if and to what extent intra-operative brain tissue stiffness measurements correlate with other tests and help identify epileptogenic brain tissue.

24 participants have already undergone intra-operative brain tonometry. Results in these participants are encouraging: abnormally high brain tissue stiffness measurements have consistently been identified and significantly associated with abnormal brain tissue.

If the tonometer adequately identifies epileptogenic brain tissue through brain tissue stiffness measurements, it is possible that resection of identified tissue could lead to better post-operative outcomes, lowering seizure recurrences and neurological deficits.


Condition or disease Intervention/treatment Phase
Epilepsy Focal Cortical Dysplasia Tuberous Sclerosis Hemimegalencephaly Polymicrogyria Rasmussen Encephalitis Sturge-Weber Syndrome Gliosis Stroke Tumor, Brain Device: Intra-operative brain tonometry Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: There are no possible controls for such a study. Post-mortem brain tissue undergoes irreversible biomechanical changes and no healthy patient undergoes comparable neurosurgical procedures. To overcome this issue, an experimental model involving intra- and inter-participant comparisons is used. A single group of participants will undergo brain tonometry and resulting brain tissue stiffness measurements will be compared in predicted normal and abnormal brain tissue (as identified by pre-operative work-up) in each participant and between participants.
Masking: None (Open Label)
Masking Description: No masking. Participants as well as caregivers and investigators will all be aware that patients are undergoing intra-operative brain tonometry (single arm study).
Primary Purpose: Diagnostic
Official Title: Use of a Tonometer to Identify Focal Cortical Dysplasia and Tuberous Sclerosis Complex During Pediatric Epilepsy Surgery
Actual Study Start Date : July 16, 2018
Estimated Primary Completion Date : March 2023
Estimated Study Completion Date : March 2023


Arm Intervention/treatment
Experimental: Brain tonometry
Participants undergoing intra-operative brain tissue stiffness measurements using a digital tonometer. Evaluated brain tissue is both presumed normal and abnormal based on results of pre-operative evaluations.
Device: Intra-operative brain tonometry
Once the brain is exposed during surgery, a sterilized digital tonometer will be used to obtain brain tissue stiffness measurements at various locations of the cortex established based on results of pre-operative work-up. Precise stereotactic coordinates for each measurement will be recorded in a neuronavigation software to facilitate comparisons with results of other tests.
Other Names:
  • Intra-operative brain tissue stiffness measurements
  • Digital tonometer




Primary Outcome Measures :
  1. Brain tissue stiffness measurements in mmHg as assessed by intraoperative use of a digital tonometer on presumed normal cerebral cortex [ Time Frame: Intraoperative ]
    Brain tonometry is a novel diagnostic approach, therefore normal and abnormal brain tissue stiffness values are not known. Measurements will be taken on presumed normal cerebral cortex, based on results of preoperative evaluations (magnetic resonance imaging, electro-encephalography, positron emission tomography), to establish potential normal brain tissue stiffness values.

  2. Brain tissue stiffness measurements in mmHg as assessed by intraoperative use of a digital tonometer on presumed pathological cerebral cortex [ Time Frame: Intraoperative ]
    Brain tonometry is a novel diagnostic approach, therefore normal and abnormal brain tissue stiffness values are not known. Measurements will be taken on presumed pathological (ex.: focal cortical dysplasia, tuberous sclerosis complex) cerebral cortex, based on results of preoperative evaluations (magnetic resonance imaging, electro-encephalography, positron emission tomography), to establish potential pathological brain tissue stiffness values.

  3. Correlation between brain tissue stiffness measurements in mmHg as assessed by novel intraoperative use of a digital tonometer and results of standard perioperative evaluations, using a 3D model of each brain [ Time Frame: Perioperative ]

    Precise stereotactic coordinates for each brain tissue stiffness measurement will be recorded in a neuronavigation software. This will allow aggregation of brain tissue stiffness measurements and results of routine preoperative (MRI, EEG, PET), as well as intra-operative tests (ECoG, histopathological analysis of resected brain tissue) on a 3D model of each patient's brain.

    With this method, each brain tissue stiffness measurement can be compared to presence or absence of an underlying lesion on MRI; to presence or absence of epileptogenic foci on EEG; to presence of iso- or hypometabolism on PET; to presence or absence of epileptogenic foci on ECoG; to pathological diagnosis and severity of cortical disorganization on histopathological analysis.

    This will give insight into how well brain tissue stiffness measurements correlate with, and potentially identify, structural and functional epileptic brain anomalies.



Secondary Outcome Measures :
  1. Surgical complications as assessed clinically on standard postoperative follow-up through study completion, up to 36 months [ Time Frame: Through study completion, up to 36 months ]
    The intraoperative use of the tonometer should not affect patient outcome. To support this, surgical complications, as they relate to the participants of this study, will be recorded on clinical follow-up, to be compared with the available literature. Number of patients with surgical complications, as well as the nature of the complications will be recorded. Of note, there are no additional visits required for this study after participation in the operating room. Follow-up remains as planned according the the nature of the patient's condition and surgery.

  2. Seizure freedom as assessed clinically on standard postoperative follow-up through study completion, up to 36 months [ Time Frame: Through study completion, up to 36 months ]
    The intraoperative use of the tonometer should not affect patient outcome. To support this, seizure freedom, as it relates to the participants of this study, will be recorded on clinical follow-up, to be compared with the available literature. Number of patients achieving seizure freedom, as well as number of patients not achieving seizure freedom will be recorded. Time to seizure recurrence will also be recorded. Of note, there are no additional visits required for this study after participation in the operating room. Follow-up remains as planned according the the nature of the patient's condition and surgery.



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants with epilepsy who candidates for surgical treatment as established by a multidisciplinary committee specialized in epilepsy.
  • Participants undergoing resective surgery for epilepsy of dysplastic (examples: focal cortical dysplasia, tuberous sclerosis, hemimegalencephaly, polymicrogyria) or non-dysplastic etiology (examples: developmental tumors, gliosis, stroke, Rasmussen encephalitis, Sturge-Weber syndrome).

Exclusion Criteria:

  • Lesion of interest located in a difficult to access region, such as paralimbic structures, insula, depth-of-sulci or inter-hemispheric.

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): NCT04344626


Contacts
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Contact: Aria Fallah, MD, MSc 13107944085 AFallah@mednet.ucla.edu
Contact: Alexander G Weil, MD 14383961644 alexandergweil@gmail.com

Locations
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United States, California
UCLA Mattel Children's Hospital Recruiting
Los Angeles, California, United States, 90095
Contact: Aria Fallah, MD, MSc    310-794-4085    AFallah@mednet.ucla.edu   
Contact: UCLA Page Operator (On Call Neurosurgey Resident)    13108256301      
Canada, Quebec
Sainte-Justine University Hospital Not yet recruiting
Montreal, Quebec, Canada, H3T1C5
Contact: Alexander G Weil, MD    14383961644    alexandergweil@gmail.com   
Sponsors and Collaborators
University of California, Los Angeles
Université de Montréal
Investigators
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Principal Investigator: Aria Fallah, MD University of California, Los Angeles
Publications:

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Responsible Party: Aria Fallah, Aria Fallah, MD, MSc, FRCSC, FAANS, FAAP; Neurosurgery, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT04344626    
Other Study ID Numbers: 17-001668-AM-00005
First Posted: April 14, 2020    Key Record Dates
Last Update Posted: April 14, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Relevant data will be shared through publications and presentations. These include brain tissue stiffness measurements in normal and abnormal brain, as well as how they correlate to results of other, standard pre- and intra-operative evaluations.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Keywords provided by Aria Fallah, University of California, Los Angeles:
Pediatric
Epilepsy
Tonometer
Focal cortical dysplasia
Tuberous sclerosis
Polymicrogyria
Rasmussen encephalitis
Sturge-Weber syndrome
Gliosis
Stroke
Developmental brain tumor
Additional relevant MeSH terms:
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Tuberous Sclerosis
Sturge-Weber Syndrome
Brain Neoplasms
Hemimegalencephaly
Epilepsy
Encephalitis
Brain Stem Infarctions
Malformations of Cortical Development
Polymicrogyria
Klippel-Trenaunay-Weber Syndrome
Sclerosis
Gliosis
Pathologic Processes
Stroke
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Hamartoma
Neoplasms
Neoplasms, Multiple Primary
Neoplastic Syndromes, Hereditary
Malformations of Cortical Development, Group I
Nervous System Malformations
Neurocutaneous Syndromes
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Congenital Abnormalities