Drug Resistant Epilepsy, Sleep, Temporal Lobe Epilepsy (TLE)
Conditions
Keywords
Epilepsy, Temporal Lobe, Epilepsy and Sleep, Drug Resistant Epilepsy, Temporal Interference, Stimulation, Hippocampus, Sleep
Brief summary
The goal of this clinical trial is to gauge whether overnight, non-invasive temporal interference (TI) stimulation aimed at the hippocampus can reduce abnormal brain activity linked to seizures and improve sleep in adults with drug-resistant temporal lobe epilepsy. The main questions are: Does overnight TI stimulation lower seizure-related EEG activity during sleep? Does overnight TI stimulation improve sleep quality and sleep patterns measured overnight in the lab? Researchers will compare each participant's nights without stimulation to nights with active stimulation, and will also look at a night after stimulation ends to see whether any changes last. Participants will: Stay in-lab for six days for overnight sleep and EEG monitoring Have one night of monitoring without stimulation Receive TI stimulation during sleep for several nights Have another night of monitoring without stimulation after the stimulation nights Complete brief questionnaires and thinking/memory tasks before and after the stimulation nights Be checked for side effects and comfort during the study and at follow-up
Interventions
DEVICENon-invasive Temporal Interference (TI) Stimulation Targeting Bilateral Hippocampi
Non-invasive temporal interference (TI) electrical stimulation delivered overnight to target the bilateral hippocampi during in-laboratory polysomnography and scalp EEG monitoring. Stimulation is applied via a multi-channel, current-controlled stimulator using a scalp electrode montage planned with MRI-guided modeling. TI is delivered continuously from lights-off to lights-on for three consecutive nights, with gradual ramp-up and ramp-down at the start and end of each session. Stimulation parameters use kilohertz carrier currents arranged to produce an amplitude-modulated envelope at 130 Hz at each hippocampal target, with current adjusted within preset safety limits based on tolerability and impedance.
Sponsors
Duke University
St. Anne's University Hospital Brno, Czech Republic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 - 70 years * Diagnosis of focal drug-resistant temporal lobe epilepsy * Candidate for in-laboratory overnight monitoring with PSG and scalp EEG, with ability to comply with study procedures * Stable antiseizure medication regimen for at least 1 week prior to admission * Capacity to provide consent
Exclusion criteria
* Generalized epilepsy syndromes or primary generalized seizures * Recent status epilepticus, seizure clusters requiring emergency intervention, or other features indicating unacceptable risk for monitored participation * Uncontrolled psychiatric illness (e.g., acute psychosis, severe untreated depression with high suicide risk) * Implanted electronic or metallic devices incompatible with TI (e.g., certain pacemakers, cochlear implants) as per device manual * Severe obstructive sleep apnea requiring immediate CPAP initiation and not yet treated * Dermatologic disease at electrode sites or known contact allergy to electrode materials * Pregnancy or breastfeeding * Concurrent enrollment in other interventional neuromodulation or pharmacological trials likely to confound EEG or sleep outcomes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Overnight Interictal Epileptiform Discharge (IED) Rate on Scalp EEG | Baseline (Night 1, no stimulation) and during active TI stimulation nights (average of Nights 2-4, overnight sleep period). | Overnight interictal epileptiform discharge (IED) rate (spikes per minute) computed from scalp EEG during sleep. IEDs will be identified using a standardized scoring pipeline, and the rate will be calculated as total IED count divided by total minutes of sleep (PSG-defined sleep time). Lower values indicate fewer epileptiform discharges (improvement). The primary comparison is baseline no-stimulation night versus the average of the active TI stimulation nights. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PSG sleep outcomes - time in REM (rapid eye movement) | Night 1 (no stimulation), Nights 2-4 (active TI), and Night 5 (no stimulation), assessed over each overnight sleep period. | Overnight polysomnography (PSG) measures of sleep stages and sleep quality/continuity. Higher sleep efficiency and lower fragmentation indicate improvement. |
| PSG sleep outcomes - efficiency | Night 1 (no stimulation), Nights 2-4 (active TI), and Night 5 (no stimulation), assessed over each overnight sleep period. | Overnight polysomnography (PSG) measures of sleep stages and sleep quality/continuity. Higher sleep efficiency and lower fragmentation indicate improvement. |
| PSG sleep outcomes - wake after sleep onset | Night 1 (no stimulation), Nights 2-4 (active TI), and Night 5 (no stimulation), assessed over each overnight sleep period. | Overnight polysomnography (PSG) measures of sleep stages and sleep quality/continuity. Higher sleep efficiency and lower fragmentation indicate improvement. |
| PSG sleep outcomes - arousal index | Night 1 (no stimulation), Nights 2-4 (active TI), and Night 5 (no stimulation), assessed over each overnight sleep period. | Overnight polysomnography (PSG) measures of sleep stages and sleep quality/continuity. Higher sleep efficiency and lower fragmentation indicate improvement. |
| Morning and evening scalp EEG biomarker burden | Evening (~20:00) and morning (~10:00) assessments across the in-lab week (Days 1-6) | Standardized scalp EEG recordings collected twice daily to quantify seizure-related biomarker burden (e.g., IED rate) and track day-to-day changes during the monitoring week. Lower biomarker burden indicates improvement. |
| Persistence of biomarker changes after stimulation ends - Post treatment night | Night 5 (no stimulation; overnight sleep period), compared with Night 1 and the average of Nights 2-4 | Biomarker burden on the post-treatment no-stimulation night to assess whether overnight TI effects carry over after stimulation stops, compared with baseline and stimulation nights. Lower biomarker burden indicates improvement |
| Cognitive performance - Rey/Taylor Figure-copy and immediate recall | Pre-stimulation (baseline, prior to Night 2) and post-stimulation (after Night 4 or on Day 6) | Scores on Rey/Taylor Figure copy and immediate recall to assess short-term changes in visuospatial construction and memory before versus after the stimulation block. Higher scores indicate better performance |
| Psychiatric symptom measures - Beck Anxiety Inventory (BAI) | Pre-stimulation (baseline, prior to Night 2) and post-stimulation (after Night 4 or on Day 6) | Scores on validated anxiety and depression scales to assess changes in symptoms before versus after the stimulation block. Lower scores indicate fewer symptoms. |
| Psychiatric symptom measures - Hamilton Anxiety Rating Scale (HAM-A) | Pre-stimulation (baseline, prior to Night 2) and post-stimulation (after Night 4 or on Day 6) | Scores on validated anxiety and depression scales to assess changes in symptoms before versus after the stimulation block. Lower scores indicate fewer symptoms. |
| Psychiatric symptom measures - Hamilton Depression Rating Scale (HAM-D) | Pre-stimulation (baseline, prior to Night 2) and post-stimulation (after Night 4 or on Day 6) | Scores on validated anxiety and depression scales to assess changes in symptoms before versus after the stimulation block. Lower scores indicate fewer symptoms. |
| Safety and tolerability - adverse events, skin checks, discomfort | During in-lab monitoring (Nights 1-5) and follow-up (Day 7) | Frequency, type, and severity of device- and study-related adverse events (e.g., skin irritation, headache, dizziness, sleep disturbance), plus tolerability/comfort checks during the admission and at follow-up |
Countries
United States
Contacts
CONTACTMatthew K Moye, BSc
PRINCIPAL_INVESTIGATORBirgit Frauscher, MD / PD
Duke University
PRINCIPAL_INVESTIGATORAdam Williamson, PhD
St. Anne's University Hospital, Brno Czechia
Outcome results
None listed