Overnight TI in TLE

Official title

Overnight Temporal Interference Stimulation of Bilateral Hippocampi to Reduce Epileptogenic Biomarkers and Improve Sleep in Temporal Lobe Epilepsy

Overview

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

• Device Non-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 param

Primary outcome measures

• Change in Overnight Interictal Epileptiform Discharge (IED) Rate on Scalp EEG [Time frame: Baseline (Night 1, no stimulation) and during active TI stimulation nights (average of Nights 2-4, overnight sleep period).]

Secondary outcome measures (11)

• PSG sleep outcomes - time in REM (rapid eye movement) [Time frame: Night 1 (no stimulation), Nights 2-4 (active TI), and Night 5 (no stimulation), assessed over each overnight sleep period.]
• PSG sleep outcomes - efficiency [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: Pre-stimulation (baseline, prior to Night 2) and post-stimulation (after Night 4 or on Day 6)]
• Psychiatric symptom measures - Beck Anxiety Inventory (BAI) [Time frame: 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) [Time frame: 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) [Time frame: 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 [Time frame: During in-lab monitoring (Nights 1-5) and follow-up (Day 7)]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Anphy Lab - Inside Hock Plaza — Durham

Publications

• 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
• 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
• 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
• 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
• 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
• 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
• 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 Hippoc PMID 39711722
• 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

Identifiers

NCT: NCT07434986 · Pro00119826

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗