Overnight TI in TLE

NCT07434986 | Not Yet Recruiting

• 1 other identifier: Pro00119826
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Conditions

Temporal Lobe Epilepsy (TLE); Drug Resistant Epilepsy; Sleep

Keywords

Epilepsy; Temporal Lobe; Epilepsy and Sleep; Drug Resistant Epilepsy; Temporal Interference; Stimulation; Hippocampus; Sleep

Outcome Measures

Primary Outcomes (1)

• 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).

Secondary Outcomes (11)

• 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.

• PSG sleep outcomes - efficiency

  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

  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

  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

  Evening (~20:00) and morning (~10:00) assessments across the in-lab week (Days 1-6)

Study Arms (1)

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.

Device: Non-invasive Temporal Interference (TI) Stimulation Targeting Bilateral Hippocampi

Interventions

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.

Single Group: Overnight TI Stimulation and Within-Subject No-Stimulation Control Nights

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Duke University: lead
• St. Anne's University Hospital Brno, Czech Republic: collaborator

Study Sites (1)

Anphy Lab - Inside Hock Plaza

Durham, North Carolina, 27705, United States

Location

Related Publications (9)

• 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.

  PMID: 36061593 BACKGROUND

• 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.

  PMID: 29244226 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.

  PMID: 25614386 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.

  PMID: 19817814 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.

  PMID: 29396478 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.

  PMID: 17634064 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.

  PMID: 39711722 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.

  PMID: 37857775 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.

  PMID: 28575667 BACKGROUND

MeSH Terms

Conditions

Epilepsy, Temporal Lobe; Drug Resistant Epilepsy; Epilepsy

Condition Hierarchy (Ancestors)

Epilepsies, Partial; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes

Study Officials

• Birgit Frauscher, MD / PD

  Duke University

  PRINCIPAL INVESTIGATOR

• Adam Williamson, PhD

  St. Anne's University Hospital, Brno Czechia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Matthew K Moye, BSc

CONTACT

919-668-9021; matthew.moye@duke.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2026
• First Posted: February 27, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 15, 2026
• Study Completion (Estimated): June 15, 2026
• Last Updated: March 18, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)