Overnight TI in TLE (TI-HPC-TLE)

May 8, 2026 updated by: Duke University

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

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

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • North Carolina
      • Durham, North Carolina, United States, 27705
        • Anphy Lab - Inside Hock Plaza
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Single Group: Overnight TI Stimulation and Within-Subject No-Stimulation Control Nights
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

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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 - efficiency
Time Frame: 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.
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.
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
Time Frame: 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.
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)
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
Time Frame: 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
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)
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)
Time Frame: 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.
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)
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)
Time Frame: 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.
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)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Duke University

Collaborators

St. Anne's University Hospital Brno, Czech Republic

Investigators

  • Principal Investigator: Birgit Frauscher, MD / PD, Duke University
  • Principal Investigator: Adam Williamson, PhD, St. Anne's University Hospital, Brno Czechia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 1, 2026

Primary Completion (Estimated)

October 30, 2026

Study Completion (Estimated)

October 30, 2026

Study Registration Dates

First Submitted

February 12, 2026

First Submitted That Met QC Criteria

February 20, 2026

First Posted (Actual)

February 27, 2026

Study Record Updates

Last Update Posted (Actual)

May 12, 2026

Last Update Submitted That Met QC Criteria

May 8, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00119826

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Sleep

Clinical Trials on Non-invasive Temporal Interference (TI) Stimulation Targeting Bilateral Hippocampi

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Lebanon

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe