search
Back to results

Sleep Architecture & Intrinsic Oscillatory and Network Connectivity in Cognition and Executive Dysfunction in TLE

Primary Purpose

Temporal Lobe Epilepsy

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Acoustic Stimulation (AS)
SHAM Stimulation
Sponsored by
University of California, Davis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Temporal Lobe Epilepsy focused on measuring Epilepsy

Eligibility Criteria

18 Years - 25 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria for TLE participants: new onset TLE (defined as less than or equal to 3 years from original TLE diagnosis based on clinical characteristics, EEG, vEEG, and high-resolution epilepsy protocol 3T MRI) epilepsy/neurology patients at UC Davis ADHD accepted Capacity to fully cooperate and follow directions, and provide consent No significant structural brain abnormalities (stroke or tumor) No circadian rhythm disorders No history of alcohol or substance abuse No claustrophobia Mesial temporal sclerosis and subtle diffuse cortical dysplasia accepted Inclusion Criteria for Healthy Controls: age, education, and sex-matched without TLE and no family history of TLE Exclusion Criteria: non-MRI compatible devices MRI safe metallic implants that distort MRI signal including braces Medications that affect cognition: topiramate, zonisamide, chronic barbiturates or benzos hearing loss/hearing aid Moderate to severe sleep apnea (apnea-hypopnea index>15 events/hour) Major neurologic disorders diagnosed or suspected Exclusion Criteria for healthy controls: History of loss of consciousness for >5 minutes

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Sham Comparator

    Arm Label

    Acoustic Stimulation (AS)

    SHAM Stimulation

    Arm Description

    Participants in this arm will be exposed to acoustic stimulation while they sleep during a night of monitoring in the UC Davis Epilepsy Monitoring Unit (EMU).

    Participants in this arm will not be exposed to any stimulation while they have their sleep monitored for one night in the UC Davis Epilepsy Monitoring Unit (EMU).

    Outcomes

    Primary Outcome Measures

    Stanford Sleepiness Scale
    Alertness Test; charts how alert a participant feels for up to 18 hours of the day for 7 days; scale is from 1-7 with higher scores meaning more sleepiness; abnormal is 4 and above
    Pittsburgh Sleep Quality Index (PSQI)
    used to measure quality and patterns of sleep in adults
    Epworth Sleepiness Scale
    subjective measure of a patient's sleepiness; scores are from 0-24 with higher scores meaning more sleepiness; abnormal is 10 and above
    Karolinska Sleepiness Scale / Sleep Diary
    Self-administered indication of sleepiness; scores are from 1-9 with higher scores meaning more sleepiness; abnormal is 7 and above
    Vigor Affect Visual Analog Scale
    self-administered assessment of mood; scores are from 0-10; depending on the question, higher score can mean more sleepiness or less sleepiness

    Secondary Outcome Measures

    Full Information

    First Posted
    February 28, 2023
    Last Updated
    September 13, 2023
    Sponsor
    University of California, Davis
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT05794295
    Brief Title
    Sleep Architecture & Intrinsic Oscillatory and Network Connectivity in Cognition and Executive Dysfunction in TLE
    Official Title
    Using Sleep Architecture Along With Intrinsic Oscillatory and Network Connectivity to Understand Cognition and Executive Dysfunction in Temporal Lobe Epilepsy
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    December 2023 (Anticipated)
    Primary Completion Date
    November 2026 (Anticipated)
    Study Completion Date
    June 2028 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    University of California, Davis

    4. Oversight

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

    5. Study Description

    Brief Summary
    Temporal Lobe Epilepsy (TLE) patients and healthy controls will undergo a night of sleep at the UC Davis Epilepsy Monitoring Unit (EMU) to characterize sleep architecture. A subset of TLE patients will be randomly assigned to an Acoustic Stimulation (AS) or SHAM stimulation night and return at least 7 days later for the other condition. Cognitive tests will be conducted 90 minutes prior to sleep (learning and immediate recall) and again 1 hour after awakening for 120 minutes (delayed recall and attention), while monitoring neural networks using functional Magnetic Resonance Imaging (fMRI).
    Detailed Description
    Temporal Lobe Epilepsy (TLE) is characterized by disordered neural network activity and temporal lobe onset seizures. Individuals with TLE experience debilitating diseases and medical conditions including sleep disruption and cognitive deficits, which compromise daily activity and quality of life. While these conditions can be long-term consequences of repeated seizures and anti-seizure medications, research demonstrates that these conditions can occur before the first recognized seizure and worsen over time, even with successful seizure treatment. This suggests that early neural network abnormalities may underlie seizure development while simultaneously impairing sleep and cognitive development, even prior to the added effects of long term disease and treatments. Individuals with TLE experience sleep disruption, which impairs memory consolidation and sustained attention, both of which are compromised in TLE. A prominent, yet untested hypothesis is that TLE-related neural network activity including interictal epileptiform discharges (IEDs) interrupt non-rapid eye movement (NREM) sleep architecture, interfering with memory consolidation and attention. However, specific mechanisms by which abnormal neural network activity contributes to disordered sleep and cognition in TLE remain elusive. Pilot data demonstrate that new-onset TLE patients exhibit cognitive deficits that are linked with reduced activation of key frontal-temporal neural networks, as measured by task-based functional magnetic resonance imaging (fMRI), which positively correlates with poor sleep. These new and exciting findings suggest that characterizing the sleep architecture patterns that contribute to less effective cognitive processing in TLE is critical to identifying modifiable sleep biomarkers, and ultimately improving cognitive function in TLE patients. This study will begin to address the existing gap in knowledge by investigating sleep architecture patterns in TLE that directly contribute to cognitive deficits using both an observational and a mechanism-probing interventional approach. In NREM sleep, slow wave oscillations on electroencephalogram (EEG) are phase-locked and coupled with sleep spindle oscillations (SW-SSO), which facilitates memory consolidation and potentially improves attention. In TLE, disordered networks leading to IEDs and seizures may contribute to altered SW-SSO coupling during sleep, resulting in memory and attention deficits. A single night of acoustic stimulation (AS) has been demonstrated to improve cognitive performance and enhance SW-SSO coupling in healthy adults, but has not been studied in TLE. The central hypothesis for this study is that disordered networks in newly diagnosed TLE patients result in altered sleep patterns, disrupting memory consolidation and attention. This study will test this hypothesis by: (1) characterizing TLE sleep patterns using computational EEG - sleep spindle density, slow wave power, IEDs, and SW-SSO coupling, (2) linking these TLE-related sleep architecture alterations to cognitive processing; (3) determining if AS enhances SW-SSO coupling in TLE; and (4) determining if AS improves memory and attention in young adults with TLE. First, we will characterize sleep architecture patterns in TLE and determine the relationship to cognitive processing. New-onset TLE patients and healthy controls will undergo one night of scalp EEG-monitored sleep to characterize sleep spindle density, slow wave power, IEDs, and SW-SSO coupling (i.e., phase-locking). Hypothesis: Compared to controls, TLE patients will exhibit IEDs as well as reduced sleep spindle density and slow wave power with reduced SW-SSO coupling. The next morning, I will use fMRI to monitor network activation as participants perform an attention task and declarative memory recall, learned the night prior. Hypothesis: Compared to controls, reduced SW-SSO coupling during sleep in TLE patients will be associated with reduced activation on task-based fMRI, as well as poorer memory and attention. Next, the study will determine the effect of AS on sleep architecture patterns and cognitive processing in TLE. New-onset TLE patients will be randomly assigned to AS or SHAM stimulation as the initial condition in a cross-over design and will undergo a night of scalp EEG monitored sleep under each condition, separated by at least one week. Hypothesis: AS will exhibit greater levels of SW-SSO coupling compared to SHAM. The next morning, I will use fMRI to monitor network activation as participants perform an attention task and declarative memory recall learned the night prior. Hypothesis: Compared to SHAM, AS will show increased activation on task-based fMRI, and improved memory and attention.

    6. Conditions and Keywords

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

    7. Study Design

    Primary Purpose
    Other
    Study Phase
    Not Applicable
    Interventional Study Model
    Crossover Assignment
    Model Description
    The first part of the study is a parallel design with new-onset TLE patients and healthy controls. The second part of the study is a crossover design with new-onset TLE patients randomized to acoustic stimulation or sham as the initial condition. At least one week later, these patients will return for a second night of evaluation with the other condition.
    Masking
    Participant
    Masking Description
    Participants will not be aware of whether they have acoustic stimulation or sham stimulation. They will be asleep while they are monitored.
    Allocation
    Randomized
    Enrollment
    72 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Acoustic Stimulation (AS)
    Arm Type
    Active Comparator
    Arm Description
    Participants in this arm will be exposed to acoustic stimulation while they sleep during a night of monitoring in the UC Davis Epilepsy Monitoring Unit (EMU).
    Arm Title
    SHAM Stimulation
    Arm Type
    Sham Comparator
    Arm Description
    Participants in this arm will not be exposed to any stimulation while they have their sleep monitored for one night in the UC Davis Epilepsy Monitoring Unit (EMU).
    Intervention Type
    Other
    Intervention Name(s)
    Acoustic Stimulation (AS)
    Intervention Description
    Acoustic Stimulation will be administered while participants have their sleep monitored during one night in the UC Davis Epilepsy Monitoring Unit (EMU).
    Intervention Type
    Other
    Intervention Name(s)
    SHAM Stimulation
    Intervention Description
    No stimulation will be administered while participants have their sleep monitored during one night in the UC Davis Epilepsy Monitoring Unit (EMU).
    Primary Outcome Measure Information:
    Title
    Stanford Sleepiness Scale
    Description
    Alertness Test; charts how alert a participant feels for up to 18 hours of the day for 7 days; scale is from 1-7 with higher scores meaning more sleepiness; abnormal is 4 and above
    Time Frame
    participant completes over one week post EMU stay
    Title
    Pittsburgh Sleep Quality Index (PSQI)
    Description
    used to measure quality and patterns of sleep in adults
    Time Frame
    screening
    Title
    Epworth Sleepiness Scale
    Description
    subjective measure of a patient's sleepiness; scores are from 0-24 with higher scores meaning more sleepiness; abnormal is 10 and above
    Time Frame
    screening
    Title
    Karolinska Sleepiness Scale / Sleep Diary
    Description
    Self-administered indication of sleepiness; scores are from 1-9 with higher scores meaning more sleepiness; abnormal is 7 and above
    Time Frame
    screening
    Title
    Vigor Affect Visual Analog Scale
    Description
    self-administered assessment of mood; scores are from 0-10; depending on the question, higher score can mean more sleepiness or less sleepiness
    Time Frame
    screening

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    25 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria for TLE participants: new onset TLE (defined as less than or equal to 3 years from original TLE diagnosis based on clinical characteristics, EEG, vEEG, and high-resolution epilepsy protocol 3T MRI) epilepsy/neurology patients at UC Davis ADHD accepted Capacity to fully cooperate and follow directions, and provide consent No significant structural brain abnormalities (stroke or tumor) No circadian rhythm disorders No history of alcohol or substance abuse No claustrophobia Mesial temporal sclerosis and subtle diffuse cortical dysplasia accepted Inclusion Criteria for Healthy Controls: age, education, and sex-matched without TLE and no family history of TLE Exclusion Criteria: non-MRI compatible devices MRI safe metallic implants that distort MRI signal including braces Medications that affect cognition: topiramate, zonisamide, chronic barbiturates or benzos hearing loss/hearing aid Moderate to severe sleep apnea (apnea-hypopnea index>15 events/hour) Major neurologic disorders diagnosed or suspected Exclusion Criteria for healthy controls: History of loss of consciousness for >5 minutes
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Colleen Stone
    Phone
    916-734-6472
    Email
    colstone@ucdavis.edu
    First Name & Middle Initial & Last Name or Official Title & Degree
    Kristina Teresinski
    Phone
    916-734-7702
    Email
    kteresinski@ucdavis.edu

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    Sleep Architecture & Intrinsic Oscillatory and Network Connectivity in Cognition and Executive Dysfunction in TLE

    We'll reach out to this number within 24 hrs