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| Name | Class |
|---|---|
| St. Anne's University Hospital Brno, Czech Republic | OTHER |
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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Single Group: Overnight TI Stimulation and Within-Subject No-Stimulation Control Nights | Experimental | Single-group, within-subject protocol with in-laboratory overnight PSG and scalp EEG. Participants complete one baseline night with no stimulation, followed by three consecutive nights of active overnight temporal interference (TI) stimulation targeting bilateral hippocampi, then one post-treatment night with no stimulation to assess persistence. Evening and morning EEG biomarker recordings are collected throughout, with safety/tolerability monitoring and pre/post cognitive and mood assessments. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Non-invasive Temporal Interference (TI) Stimulation Targeting Bilateral Hippocampi | Device | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Overnight Interictal Epileptiform Discharge (IED) Rate on Scalp EEG | 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. | Baseline (Night 1, no stimulation) and during active TI stimulation nights (average of Nights 2-4, overnight sleep period). |
| Measure | Description | Time Frame |
|---|---|---|
| PSG sleep outcomes - time in REM (rapid eye movement) | Overnight polysomnography (PSG) measures of sleep stages and sleep quality/continuity. Higher sleep efficiency and lower fragmentation indicate improvement. | Night 1 (no stimulation), Nights 2-4 (active TI), and Night 5 (no stimulation), assessed over each overnight sleep period. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Matthew K Moye, BSc | Contact | 919-668-9021 | matthew.moye@duke.edu |
| Name | Affiliation | Role |
|---|---|---|
| Birgit Frauscher, MD / PD | Duke University | Principal Investigator |
| Adam Williamson, PhD | St. Anne's University Hospital, Brno Czechia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Anphy Lab - Inside Hock Plaza | Durham | North Carolina | 27705 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36061593 | Background | Acerbo E, Jegou A, Luff C, Dzialecka P, Botzanowski B, Missey F, Ngom I, Lagarde S, Bartolomei F, Cassara A, Neufeld E, Jirsa V, Carron R, Grossman N, Williamson A. Focal non-invasive deep-brain stimulation with temporal interference for the suppression of epileptic biomarkers. Front Neurosci. 2022 Aug 17;16:945221. doi: 10.3389/fnins.2022.945221. eCollection 2022. | |
| 29244226 |
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| ID | Term |
|---|---|
| D004833 | Epilepsy, Temporal Lobe |
| D000069279 | Drug Resistant Epilepsy |
| D004827 | Epilepsy |
| ID | Term |
|---|---|
| D004828 | Epilepsies, Partial |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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|
| PSG sleep outcomes - efficiency |
Overnight polysomnography (PSG) measures of sleep stages and sleep quality/continuity. Higher sleep efficiency and lower fragmentation indicate improvement. |
| Night 1 (no stimulation), Nights 2-4 (active TI), and Night 5 (no stimulation), assessed over each overnight sleep period. |
| PSG sleep outcomes - wake after sleep onset | Overnight polysomnography (PSG) measures of sleep stages and sleep quality/continuity. Higher sleep efficiency and lower fragmentation indicate improvement. | Night 1 (no stimulation), Nights 2-4 (active TI), and Night 5 (no stimulation), assessed over each overnight sleep period. |
| PSG sleep outcomes - arousal index | Overnight polysomnography (PSG) measures of sleep stages and sleep quality/continuity. Higher sleep efficiency and lower fragmentation indicate improvement. | Night 1 (no stimulation), Nights 2-4 (active TI), and Night 5 (no stimulation), assessed over each overnight sleep period. |
| Morning and evening scalp EEG biomarker burden | 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. | Evening (~20:00) and morning (~10:00) assessments across the in-lab week (Days 1-6) |
| Persistence of biomarker changes after stimulation ends - Post treatment night | 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 | Night 5 (no stimulation; overnight sleep period), compared with Night 1 and the average of Nights 2-4 |
| Cognitive performance - Rey/Taylor Figure-copy and immediate recall | 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 | Pre-stimulation (baseline, prior to Night 2) and post-stimulation (after Night 4 or on Day 6) |
| Psychiatric symptom measures - Beck Anxiety Inventory (BAI) | Scores on validated anxiety and depression scales to assess changes in symptoms before versus after the stimulation block. Lower scores indicate fewer symptoms. | Pre-stimulation (baseline, prior to Night 2) and post-stimulation (after Night 4 or on Day 6) |
| Psychiatric symptom measures - Hamilton Anxiety Rating Scale (HAM-A) | Scores on validated anxiety and depression scales to assess changes in symptoms before versus after the stimulation block. Lower scores indicate fewer symptoms. | Pre-stimulation (baseline, prior to Night 2) and post-stimulation (after Night 4 or on Day 6) |
| Psychiatric symptom measures - Hamilton Depression Rating Scale (HAM-D) | Scores on validated anxiety and depression scales to assess changes in symptoms before versus after the stimulation block. Lower scores indicate fewer symptoms. | Pre-stimulation (baseline, prior to Night 2) and post-stimulation (after Night 4 or on Day 6) |
| Safety and tolerability - adverse events, skin checks, discomfort | 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 | During in-lab monitoring (Nights 1-5) and follow-up (Day 7) |
| Roehri N, Pizzo F, Lagarde S, Lambert I, Nica A, McGonigal A, Giusiano B, Bartolomei F, Benar CG. High-frequency oscillations are not better biomarkers of epileptogenic tissues than spikes. Ann Neurol. 2018 Jan;83(1):84-97. doi: 10.1002/ana.25124. |
| 25614386 | Background | Colombet B, Woodman M, Badier JM, Benar CG. AnyWave: a cross-platform and modular software for visualizing and processing electrophysiological signals. J Neurosci Methods. 2015 Mar 15;242:118-26. doi: 10.1016/j.jneumeth.2015.01.017. Epub 2015 Jan 19. |
| 19817814 | Background | McLachlan RS, Pigott S, Tellez-Zenteno JF, Wiebe S, Parrent A. Bilateral hippocampal stimulation for intractable temporal lobe epilepsy: impact on seizures and memory. Epilepsia. 2010 Feb;51(2):304-7. doi: 10.1111/j.1528-1167.2009.02332.x. Epub 2009 Oct 8. |
| 29396478 | Background | Voroslakos M, Takeuchi Y, Brinyiczki K, Zombori T, Oliva A, Fernandez-Ruiz A, Kozak G, Kincses ZT, Ivanyi B, Buzsaki G, Berenyi A. Direct effects of transcranial electric stimulation on brain circuits in rats and humans. Nat Commun. 2018 Feb 2;9(1):483. doi: 10.1038/s41467-018-02928-3. |
| 17634064 | Background | Velasco AL, Velasco F, Velasco M, Trejo D, Castro G, Carrillo-Ruiz JD. Electrical stimulation of the hippocampal epileptic foci for seizure control: a double-blind, long-term follow-up study. Epilepsia. 2007 Oct;48(10):1895-903. doi: 10.1111/j.1528-1167.2007.01181.x. Epub 2007 Jul 18. |
| 39711722 | Background | Missey F, Acerbo E, Dickey A, Trajlinek J, Studnicka O, Lubrano C, De Araujo E Silva M, Brady E, Vsiansky V, Szabo JP, Dolezalova I, Fabo D, Pail M, Gutekunst CA, Migliore R, Migliore M, Lagarde S, Carron R, Karimi F, Astorga R, Cassara A, Kuster N, Neufeld E, Bartolomei F, Pedersen NP, Gross R, Jirsa V, Drane D, Brazdil M, Williamson A. Non-invasive Temporal Interference Stimulation of the Hippocampus Suppresses Epileptic Biomarkers in Patients with Epilepsy: Biophysical Differences between Kilohertz and Amplitude Modulated Stimulation. medRxiv [Preprint]. 2025 Jan 14:2024.12.05.24303799. doi: 10.1101/2024.12.05.24303799. |
| 37857775 | Background | Violante IR, Alania K, Cassara AM, Neufeld E, Acerbo E, Carron R, Williamson A, Kurtin DL, Rhodes E, Hampshire A, Kuster N, Boyden ES, Pascual-Leone A, Grossman N. Non-invasive temporal interference electrical stimulation of the human hippocampus. Nat Neurosci. 2023 Nov;26(11):1994-2004. doi: 10.1038/s41593-023-01456-8. Epub 2023 Oct 19. |
| 28575667 | Background | Grossman N, Bono D, Dedic N, Kodandaramaiah SB, Rudenko A, Suk HJ, Cassara AM, Neufeld E, Kuster N, Tsai LH, Pascual-Leone A, Boyden ES. Noninvasive Deep Brain Stimulation via Temporally Interfering Electric Fields. Cell. 2017 Jun 1;169(6):1029-1041.e16. doi: 10.1016/j.cell.2017.05.024. |
| D000073376 | Epileptic Syndromes |