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Network Neuro-modulation for Mesial Temporal Lobe Epilepsy

Primary Purpose

Mesial Temporal Lobe Epilepsy

Status
Not yet recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Low Frequency Stimulation (LFS) of site with the Medtronic Percept PC system
Standard of Care (SOC) High Frequency Stimulation of the Anterior Nucleus of the Thalamus (ANT) with the Medtronic Percept PC system
Sponsored by
The University of Texas Health Science Center, Houston
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mesial Temporal Lobe Epilepsy

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients with a presumptive diagnosis of EPH determined by the group of clinicians who participate in patient management conference. Ability to comply with test directions and provide informed consent or assent to the study, i.e. cognitively able to participate in studies [typically intelligence quotient (IQ) of 65 or above]. Relatively preserved verbal memory - as determined via formal neuropsychological evaluation performed by the neuropsychologist. The values must within 1 standard deviation (SD) of the mean for verbal memory Proficient in English, as all of our tasks and consent forms will be in English and the inclusion of non-English speakers will introduce another confound in this small sample size and preclude grouped analysis Age 18 - 65 years (we expect the trial to take 5 years and wish to target patients with minimal medical co-morbidities) Must have a minimum of 2 seizures of any type per month - this is essential to be able to detect the impact of neuromodulation on the epilepsy over relatively short intervals of time. Patients with secondary generalized seizures may also be enrolled so long as they have a maximum of 20 generalized seizures in the past 12 months (prior to enrollment), or an average of no more than 3 generalized seizures per month. Exclusion Criteria: Impaired reading and cognitive functions (more than 3 standard deviations below the mean, usually an IQ < 60), as determined by preoperative neuropsychological testing. Patients with gross structural abnormalities (hamartomata, tumors, vascular malformations, diffuse malformations of cortical development) in the brain that raise the possibility of dual pathology resulting in the epilepsy and by derivation, a larger epilepsy network. Patients with neurological conditions such as recent history (within past 5 years) of a stroke, encephalitis and meningitis. Any patient with a current diagnosis of these conditions will also be excluded. Patients with any episodes of status epilepticus in the past 12 months prior to enrollment. Patients with uncontrolled prominent psychiatric comorbidity that will preclude their meaningful participation. Patients with a Beck Depression Inventory II score at baseline examination greater than or equal to 29 (i.e., severe depression). Patients who have attempted suicide in the past 12 months. Patients with memory impairment due to other neurological conditions such as dementia and Parkinson's disease. Patients who are unable to speak or comprehend English. The inclusion of multiple languages will make task development and grouped comparisons of neuro-psychology data difficult. Patients with cardiac pacemakers, intracranial aneurysm clips, or other potentially mobile implanted metallic devices that are deemed MRI incompatible by the manufactures. The absence of high resolution structural imaging precludes appropriate targeting of the regions of interest. Classic hippocampal sclerosis [equivalent to International League Against Epilepsy (ILAE) type 1] by imaging. Prior brain surgery for any reason or failed prior brain neuromodulation [prior vagus nerve stimulation (VNS) therapy is acceptable so long as it is held constant for the duration of the trial]. History of or current non-epileptic spells (will confound accuracy of seizure detection with ANT Percept PC and the precision of the estimate of the neuromodulation effect). Patients who are pregnant. All female participants of childbearing potential will be counselled prior to enrollment regarding the unknown risks of treatment on a fetus and the importance of using contraception while they are a subject in this study. If a female participant becomes pregnant during the study, they will returned to FDA-approved ANT stimulation parameters (standard of care).

Sites / Locations

  • Mayo Clinic
  • The University of Texas Science Center at Houston

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Site 1, then SOC, then site 2, then SOC, then site 3, then SOC, then site 4, then SOC, then site 1

Site 1, then SOC, then site 2, then SOC, then site 3, then SOC, then site 4, then SOC, then site 2

Site 1, then SOC, then site 2, then SOC, then site 3, then SOC, then site 4, then SOC, then site 3

Site 1, then SOC, then site 2, then SOC, then site 3, then SOC, then site 4, then SOC, then site 4

Arm Description

Outcomes

Primary Outcome Measures

Number of seizures as self-reported by participants
Number of seizures as self-reported by participants
Number of seizures as self-reported by participants
Number of seizures as self-reported by participants
Number of seizures as self-reported by participants
Number of seizures as self-reported by participants
Number of seizures as self-reported by participants
Number of seizures as self-reported by participants
Number of seizures as self-reported by participants
Number of seizures as assessed by EEG
Number of seizures as assessed by EEG
Number of seizures as assessed by the Percept PC
Number of seizures as assessed by the Percept PC
Number of inter-ictal spikes as assessed by the Percept PC
Number of inter-ictal spikes as assessed by the Percept PC

Secondary Outcome Measures

Verbal memory as assessed by score on the California Verbal Learning Test second edition
Individuals read a list of 16 words and are asked to repeat them immediately for each of 5 trials.
Verbal memory as assessed by score on the California Verbal Learning Test second edition
Individuals read a list of 16 words and are asked to repeat them immediately for each of 5 trials.
Verbal memory as assessed by score on the Logical Memory I and II subtests from the Wechsler Memory Scale - IV
Verbal memory as assessed by score on the Logical Memory I and II subtests from the Wechsler Memory Scale - IV
Wellness as assessed by score on the the Quality of Life in Epilepsy 31 (QOLIE-31) survey
QOLIE-31 total score ranges from 0 to 100, with a higher score indicating a more favorable quality of life.
Wellness as assessed by score on the Quality of Life in Epilepsy 31 (QOLIE-31) survey
QOLIE-31 total score ranges from 0 to 100, with a higher score indicating a more favorable quality of life.
Wellness as assessed by score on the 36-Item Short Form Health Survey (SF-36)
SF-36 total score ranges from 0 to 100, with a higher score indicating a better health status.
Wellness as assessed by score on the 36-Item Short Form Health Survey (SF-36)
SF-36 total score ranges from 0 to 100, with a higher score indicating a better health status.

Full Information

First Posted
November 1, 2022
Last Updated
May 9, 2023
Sponsor
The University of Texas Health Science Center, Houston
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
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1. Study Identification

Unique Protocol Identification Number
NCT05608408
Brief Title
Network Neuro-modulation for Mesial Temporal Lobe Epilepsy
Official Title
Network Neuro-modulation for Mesial Temporal Lobe Epilepsy
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 1, 2023 (Anticipated)
Primary Completion Date
August 31, 2027 (Anticipated)
Study Completion Date
August 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The University of Texas Health Science Center, Houston
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
In this study, participants will receive unilateral Deep Brain Stimulation (DBS) for treatment of epilepsy, with network-based stimulation targets specifically defined using a stereo-electro-encephalographic evaluation and chronic recordings using the Medtronic Percept™ primary cell (PC) Neurostimulator DBS System with BrainSense™ Technology. The hypothesis is that, compared to no stimulation or to standard duty cycle high frequency stimulation, epilepsy neuromodulation using low frequency stimulation and informed by network architecture in patients with epilepsy that arises in a hippocampus that also subserves memory - epilepsy in a precious hippocampus (EPH) - will result in a significant decrease in seizure frequency and severity, paralleled by a decrease in EEG spike counts and improved memory function.
Detailed Description
Different stimulation types will be administered in a crossover fashion, as follows. There will be four four-month periods of low-frequency DBS stimulation, and in each of these four-month periods, stimulation will occur at one of four different sites [the anterior nucleus of the thalamus (ANT), entorhinal cortex (ERC), piriform cortex (PiC), and hippocampal fornix (HCF)], with the order of receipt differing among study participants. There will be a 3-month washout period after each 4-month stimulation period, with the washout being standard of care (SOC) high-frequency DBS stimulation of the ANT. Finally, there will be a 7 to 12 month DBS stimulation period with the stimulation type that yielded the best results.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mesial Temporal Lobe Epilepsy

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
Participant
Allocation
Non-Randomized
Enrollment
8 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Site 1, then SOC, then site 2, then SOC, then site 3, then SOC, then site 4, then SOC, then site 1
Arm Type
Experimental
Arm Title
Site 1, then SOC, then site 2, then SOC, then site 3, then SOC, then site 4, then SOC, then site 2
Arm Type
Experimental
Arm Title
Site 1, then SOC, then site 2, then SOC, then site 3, then SOC, then site 4, then SOC, then site 3
Arm Type
Experimental
Arm Title
Site 1, then SOC, then site 2, then SOC, then site 3, then SOC, then site 4, then SOC, then site 4
Arm Type
Experimental
Intervention Type
Device
Intervention Name(s)
Low Frequency Stimulation (LFS) of site with the Medtronic Percept PC system
Intervention Description
Stimulation of site with the Medtronic Percept PC system using low frequency stimulation at 0.5 Hz.
Intervention Type
Device
Intervention Name(s)
Standard of Care (SOC) High Frequency Stimulation of the Anterior Nucleus of the Thalamus (ANT) with the Medtronic Percept PC system
Intervention Description
Stimulation of the Anterior Nucleus of the Thalamus (ANT) with the Medtronic Percept PC system using standard of care high frequency stimulation parameters.
Primary Outcome Measure Information:
Title
Number of seizures as self-reported by participants
Time Frame
baseline
Title
Number of seizures as self-reported by participants
Time Frame
2 weeks
Title
Number of seizures as self-reported by participants
Time Frame
4 weeks
Title
Number of seizures as self-reported by participants
Time Frame
6 weeks
Title
Number of seizures as self-reported by participants
Time Frame
8 weeks
Title
Number of seizures as self-reported by participants
Time Frame
10 weeks
Title
Number of seizures as self-reported by participants
Time Frame
12 weeks
Title
Number of seizures as self-reported by participants
Time Frame
14 weeks
Title
Number of seizures as self-reported by participants
Time Frame
16 weeks
Title
Number of seizures as assessed by EEG
Time Frame
baseline
Title
Number of seizures as assessed by EEG
Time Frame
4 months
Title
Number of seizures as assessed by the Percept PC
Time Frame
baseline
Title
Number of seizures as assessed by the Percept PC
Time Frame
4 months
Title
Number of inter-ictal spikes as assessed by the Percept PC
Time Frame
baseline
Title
Number of inter-ictal spikes as assessed by the Percept PC
Time Frame
4 months
Secondary Outcome Measure Information:
Title
Verbal memory as assessed by score on the California Verbal Learning Test second edition
Description
Individuals read a list of 16 words and are asked to repeat them immediately for each of 5 trials.
Time Frame
baseline
Title
Verbal memory as assessed by score on the California Verbal Learning Test second edition
Description
Individuals read a list of 16 words and are asked to repeat them immediately for each of 5 trials.
Time Frame
4 months
Title
Verbal memory as assessed by score on the Logical Memory I and II subtests from the Wechsler Memory Scale - IV
Time Frame
baseline
Title
Verbal memory as assessed by score on the Logical Memory I and II subtests from the Wechsler Memory Scale - IV
Time Frame
4 months
Title
Wellness as assessed by score on the the Quality of Life in Epilepsy 31 (QOLIE-31) survey
Description
QOLIE-31 total score ranges from 0 to 100, with a higher score indicating a more favorable quality of life.
Time Frame
baseline
Title
Wellness as assessed by score on the Quality of Life in Epilepsy 31 (QOLIE-31) survey
Description
QOLIE-31 total score ranges from 0 to 100, with a higher score indicating a more favorable quality of life.
Time Frame
4 months
Title
Wellness as assessed by score on the 36-Item Short Form Health Survey (SF-36)
Description
SF-36 total score ranges from 0 to 100, with a higher score indicating a better health status.
Time Frame
baseline
Title
Wellness as assessed by score on the 36-Item Short Form Health Survey (SF-36)
Description
SF-36 total score ranges from 0 to 100, with a higher score indicating a better health status.
Time Frame
4 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with a presumptive diagnosis of EPH determined by the group of clinicians who participate in patient management conference. Ability to comply with test directions and provide informed consent or assent to the study, i.e. cognitively able to participate in studies [typically intelligence quotient (IQ) of 65 or above]. Relatively preserved verbal memory - as determined via formal neuropsychological evaluation performed by the neuropsychologist. The values must within 1 standard deviation (SD) of the mean for verbal memory Proficient in English, as all of our tasks and consent forms will be in English and the inclusion of non-English speakers will introduce another confound in this small sample size and preclude grouped analysis Age 18 - 65 years (we expect the trial to take 5 years and wish to target patients with minimal medical co-morbidities) Must have a minimum of 2 seizures of any type per month - this is essential to be able to detect the impact of neuromodulation on the epilepsy over relatively short intervals of time. Patients with secondary generalized seizures may also be enrolled so long as they have a maximum of 20 generalized seizures in the past 12 months (prior to enrollment), or an average of no more than 3 generalized seizures per month. Exclusion Criteria: Impaired reading and cognitive functions (more than 3 standard deviations below the mean, usually an IQ < 60), as determined by preoperative neuropsychological testing. Patients with gross structural abnormalities (hamartomata, tumors, vascular malformations, diffuse malformations of cortical development) in the brain that raise the possibility of dual pathology resulting in the epilepsy and by derivation, a larger epilepsy network. Patients with neurological conditions such as recent history (within past 5 years) of a stroke, encephalitis and meningitis. Any patient with a current diagnosis of these conditions will also be excluded. Patients with any episodes of status epilepticus in the past 12 months prior to enrollment. Patients with uncontrolled prominent psychiatric comorbidity that will preclude their meaningful participation. Patients with a Beck Depression Inventory II score at baseline examination greater than or equal to 29 (i.e., severe depression). Patients who have attempted suicide in the past 12 months. Patients with memory impairment due to other neurological conditions such as dementia and Parkinson's disease. Patients who are unable to speak or comprehend English. The inclusion of multiple languages will make task development and grouped comparisons of neuro-psychology data difficult. Patients with cardiac pacemakers, intracranial aneurysm clips, or other potentially mobile implanted metallic devices that are deemed MRI incompatible by the manufactures. The absence of high resolution structural imaging precludes appropriate targeting of the regions of interest. Classic hippocampal sclerosis [equivalent to International League Against Epilepsy (ILAE) type 1] by imaging. Prior brain surgery for any reason or failed prior brain neuromodulation [prior vagus nerve stimulation (VNS) therapy is acceptable so long as it is held constant for the duration of the trial]. History of or current non-epileptic spells (will confound accuracy of seizure detection with ANT Percept PC and the precision of the estimate of the neuromodulation effect). Patients who are pregnant. All female participants of childbearing potential will be counselled prior to enrollment regarding the unknown risks of treatment on a fetus and the importance of using contraception while they are a subject in this study. If a female participant becomes pregnant during the study, they will returned to FDA-approved ANT stimulation parameters (standard of care).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Eliana M Klier, PhD
Phone
713-500-5442
Email
Eliana.Klier@uth.tmc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nitin Tandon, MD
Organizational Affiliation
The University of Texas Health Science Center, Houston
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gregory Worrell, MD, PhD
Email
worrell.gregory@mayo.edu
Facility Name
The University of Texas Science Center at Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eliana M Klier, PhD

12. IPD Sharing Statement

Plan to Share IPD
No

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Network Neuro-modulation for Mesial Temporal Lobe Epilepsy

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