An interventional study of Anterior thalamic deep brain stimulation with a standardized amplitude schedule and acute stimulation challenges in Drug Resistant Epilepsy and Focal Epilepsy, sponsored by Yonsei University. Not yet recruiting at 1 site in South Korea. Open to participants aged 19 Years and older. Per ClinicalTrials.gov, last updated 2026-11-03.
Sponsored by Yonsei University · Not applicable, Interventional, and Basic science
This prospective, single-center mechanistic pilot study will investigate the electrophysiological dose-response to anterior thalamic deep brain stimulation (ANT-DBS) in 10 adults with drug-resistant focal epilepsy undergoing clinically indicated DBS implantation.
Using local field potentials (LFPs) recorded from implanted sensing-enabled DBS leads, investigators will assess stimulation-induced changes in slow-gamma (20-50 Hz) power. Standardized acute stimulation challenges will be performed at DBS activation (2.0 mA), 1 month after activation (2.0 and 3.5 mA), and 3 months after activation (2.0, 3.5, and up to 5.0 mA, as tolerated). Each amplitude will be tested at least twice against a stimulation-OFF baseline.
The primary objective is to characterize the amplitude-dependent electrophysiological response, with the hypothesis that higher stimulation amplitudes produce greater slow-gamma suppression. Secondary objectives include assessing response reproducibility, characterizing longitudinal LFP adaptation during the first 3 months, investigating associations with electrode location and modeled electric fields, and exploring relationships with seizure-frequency reduction during months 7-12 after stimulation activation.
Study Design This is a prospective, single-center, single-arm mechanistic pilot study involving 10 adults with drug-resistant focal epilepsy. Bilateral anterior thalamic deep brain stimulation (ANT-DBS) implantation using a sensing-enabled neurostimulator (Medtronic Percept PC) is determined as part of standard clinical care, independently of study participation.
The study consists of two periods. During the standardized stimulation period (activation to 3 months), stimulation frequency (145 Hz), pulse width (90 μs), and cycling follow the SANTE protocol, with scheduled chronic stimulation amplitudes of 2.0 mA at activation and 3.5 mA at 1 month. Adjustments are permitted whenever clinically necessary. From 3 to 12 months, stimulation parameters are managed according to routine clinical care, with all changes documented.
Study Visits Research assessments are performed during scheduled clinical visits. Before implantation, participants undergo baseline clinical, seizure-frequency, neuropsychological, and mood assessments. Within 1 week after implantation, two 120-second stimulation-OFF recordings are obtained to select sensing contacts and determine the chronic sensing frequency band.
Acute stimulation challenges are performed at activation (2.0 mA), 1 month after activation (2.0 and 3.5 mA), and 3 months after activation (2.0, 3.5, and up to 5.0 mA). The final clinical and electrophysiological assessments are performed at 12 months after activation.
Acute Stimulation Challenge Each stimulation condition is assessed against a stable, 2-minute stimulation-OFF baseline, followed by continuous stimulation at the target amplitude and 60 seconds of stable local field potential (LFP) recording after the target amplitude is reached. Stimulation is then switched OFF for a minimum 5-minute washout interval, with the final 2 minutes serving as the local baseline for the subsequent block when stability criteria are met.
Each amplitude is tested at least twice using a prespecified counterbalanced sequence. At the 3-month visit, the high-amplitude condition targets 5.0 mA, approached in 0.5-mA increments from 3.5 mA. If 5.0 mA is not tolerated bilaterally, the maximum amplitude tolerated on both sides is used and analyzed separately from the complete-dose primary analysis.
Challenges are conducted under direct medical supervision with predefined safety criteria. Transient mild adverse symptoms require immediate interruption of the affected block, while persistent or clinically significant symptoms, mood or behavioral changes, or seizures require termination of the session and appropriate clinical management.
Electrophysiological and Imaging Analyses The primary electrophysiological measure is the stimulation-induced change in 20-50 Hz slow-gamma power, calculated as the natural logarithm of the ratio of stimulation-ON to local stimulation-OFF integrated band power.
Within-session reproducibility and longitudinal electrophysiological adaptation are evaluated using repeated acute recordings and device-derived chronic sensing data. Correspondence between broadband acute slow-gamma measures and device-matched narrow-band measures is assessed before examining their longitudinal relationships.
Electrode locations are reconstructed using postoperative CT co-registered to preoperative MRI. Electric-field or volume-of-tissue-activated modeling is performed using Lead-DBS or an equivalent validated pipeline to explore relationships between anatomical network engagement and electrophysiological responses.
Statistical Analysis The primary dose-response analysis uses repeated stimulation challenges obtained at the 3-month visit. A linear mixed-effects model includes stimulation amplitude as a categorical fixed effect and participant as a random intercept, using restricted maximum likelihood estimation with Kenward-Roger or Satterthwaite degrees-of-freedom adjustment.
Given the pilot sample size (N=10), interpretation emphasizes estimated effects, 95% confidence intervals, within-participant reproducibility, and individual response trajectories rather than statistical significance alone.
The primary frequency band, response metric, and analysis framework are prespecified and will not be modified based on observed clinical outcomes. Associations between electrophysiological measures and seizure-frequency reduction during months 7-12 are considered exploratory.
275 studies on the registry are indexed under Drug Resistant Epilepsy; 104 are open to participants now.
This study's planned enrollment of 10 is below the median of 30 across 217 interventional studies indexed under Drug Resistant Epilepsy.
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Exclusion Criteria:
Adults with drug-resistant focal epilepsy undergoing clinically indicated bilateral anterior thalamic DBS implantation using a sensing-enabled Medtronic Percept PC system. Research procedures include a protocol-defined stimulation amplitude titration schedule during the first 3 months, with adjustments permitted for clinical safety, and repeated acute stimulation challenges with concurrent local field potential (LFP) recording at activation and 1 and 3 months after activation.
Device: Anterior thalamic deep brain stimulation with a standardized amplitude schedule and acute stimulation challenges
ANT-DBS implantation using the sensing-enabled Medtronic Percept PC is standard care, independent of study participation. Study-specific procedures include scheduled chronic stimulation (145 Hz, 90 μs, cycling) at 2.0 mA from activation and 3.5 mA from month 1, with clinical adjustments permitted. At month 3, the physician selects 3.0-4.0 mA, followed by routine management. Acute challenges at activation, month 1, and month 3 test 2.0 mA; 2.0/3.5 mA; and 2.0/3.5/up to 5.0 mA, respectively. Each amplitude is repeated at least twice, with counterbalanced sequences at months 1 and 3. Each block includes a 2-minute local stimulation-OFF baseline, continuous stimulation with 60 seconds of stable LFP recording at the target amplitude, and at least 5 minutes of OFF washout between blocks. If bilateral 5.0 mA is not tolerated, the maximum common tolerated amplitude is used. Challenges may be modified or stopped for safety.
Stimulation-Induced Change in Anterior Thalamic Slow-Gamma (20-50 Hz) Power at 2.0, 3.5 and 5.0 mA
Stimulation-induced change in anterior thalamic local field potential (LFP) power in the 20-50 Hz slow-gamma band, quantified as ΔSG = ln(P\_ON/P\_OFF), where P\_ON and P\_OFF are integrated band power during 60 s of stable continuous stimulation and during the immediately preceding 2-minute stimulation-off baseline, respectively, recorded with the implanted device (BrainSense Streaming). At the 3-month visit, ΔSG is measured at 2.0, 3.5 and 5.0 mA, with at least two repetitions per amplitude in a counterbalanced order; repeats are averaged within each hemisphere and then across hemispheres. Participants who cannot tolerate bilateral 5.0 mA are tested at the highest amplitude tolerated on both sides and analyzed separately in prespecified available-dose sensitivity analyses. Zero indicates no change; negative values indicate suppression.
Time frame: 3 months after stimulation activation
Test-Retest Agreement of the Acute Slow-Gamma Response
Intraclass correlation coefficient (two-way mixed-effects, absolute agreement, single measure) between the two repeated measurements of ΔSG (defined in the primary outcome) at the same amplitude and visit, calculated for each amplitude at each visit.
Time frame: At stimulation activation, and 1 and 3 months after activation
Difference in Slow-Gamma Response Between 3.5 and 2.0 mA at 1 Month
Within-participant difference in repeat-averaged ΔSG (defined in the primary outcome) between 3.5 and 2.0 mA (3.5 minus 2.0 mA), tested at the same visit as supportive replication of the primary dose-response.
Time frame: 1 month after stimulation activation
Amplitude-Response Slope of the Slow-Gamma Response
Per-participant slope of repeat-averaged ΔSG (defined in the primary outcome) against stimulation amplitude across 2.0, 3.5 and 5.0 mA, in log ratio per mA.
Time frame: 3 months after stimulation activation
Change in Slow-Gamma Response to 2.0 mA Stimulation Across Visits
Repeat-averaged ΔSG (defined in the primary outcome) at 2.0 mA at each visit, each normalized to its own local stimulation-off baseline, describing how the response to the same amplitude changes with cumulative chronic stimulation.
Time frame: At stimulation activation, and 1 and 3 months after activation
Device-Matched Narrow-Band Power Change During Acute Challenges
Power in an approximately 5-Hz band centered on each participant's chronic sensing frequency, recomputed offline from the same challenge recordings and expressed as ln(ON/OFF). Its agreement with ΔSG is assessed by Spearman correlation and direction concordance.
Time frame: At stimulation activation, and 1 and 3 months after activation
Change in Chronic Narrow-Band Anterior Thalamic Power During the First 3 Months of Stimulation
Narrow-band power stored by the device during daily life (BrainSense Timeline), normalized to the stimulation-free period after implantation; change from a prespecified early stimulation window to a window at month 3. Its relation to ΔSG is assessed by Spearman correlation.
Time frame: From the stimulation-free period after implantation to 3 months after stimulation activation
Percent Reduction in Monthly Seizure Frequency in Months 7-12
(Baseline monthly seizure frequency - mean monthly seizure frequency in months 7-12) / baseline × 100, from seizure diaries; positive values indicate reduction. Baseline uses a prospective diary of at least 8 weeks (target 12 weeks) before implantation where available, and otherwise systematically recorded diaries or medical records. Its relation to the acute and chronic LFP measures is assessed by Spearman correlation.
Time frame: Preoperative baseline and months 7-12 after stimulation activation
Overlap of the Modeled Stimulation Field With the Anterior Thalamic Nucleus and Mammillothalamic Tract
Overlap of the modeled electric field (volume of tissue activated) with the anterior thalamic nucleus and with the mammillothalamic tract for each challenge condition, expressed as the percentage of each structure's volume, estimated with Lead-DBS from postoperative CT co-registered to preoperative MRI. Active-contact location and diffusion tensor imaging (DTI) structural connectivity are analyzed as additional explanatory measures. Relation to ΔSG is assessed by Spearman correlation.
Time frame: Postoperative imaging, modeled for challenge conditions at activation and 1 and 3 months after activation
Percent Reduction in Focal-to-Bilateral Tonic-Clonic Seizure Frequency
Same calculation as the main seizure outcome, restricted to focal-to-bilateral tonic-clonic seizures, in participants who have them at baseline; prespecified sensitivity anchor
Time frame: Preoperative baseline and months 7-12 after stimulation activation
Percent Reduction in Caregiver-Corroborated or Witnessed Disabling Seizure Frequency
Same calculation, restricted to disabling seizures witnessed or confirmed by a cohabiting or primary caregiver; prespecified sensitivity anchor
Time frame: Preoperative baseline and months 7-12 after stimulation activation
Burden of Device-Recorded Electrographic Seizure-Like Events and Epileptiform Transients
Number of electrographic seizure-like events or epileptiform transients per hour of analyzable recording (per analyzable segment for event-triggered recordings), using prespecified criteria. Where possible, events are adjudicated independently by two clinical neurophysiologists blinded to clinical outcomes. Calculated only for participants with raw time-domain or event-specific LFP recordings; agreement with diary-based seizure outcomes is assessed.
Time frame: From implantation to 12 months after stimulation activation
Proportion of Planned Acute Challenges Completed With Two Valid Repeats at Each Amplitude
Challenges with two valid repeats at every planned amplitude, divided by challenges planned
Time frame: At stimulation activation, and 1 and 3 months after activation
Proportion of Participants Reaching 5.0 mA on Both Sides
Reasons for not reaching it (adverse event, seizure worsening, clinical judgment or technical limitation) are reported
Time frame: 3 months after stimulation activation
Proportion of Recordings With Analyzable Bilateral Local Field Potential Signals
Recordings meeting prespecified signal-quality criteria in both hemispheres, divided by recordings performed
Time frame: Within 1 week after implantation, and at stimulation activation and 1 and 3 months after activation
Proportion of Participants With Usable Bilateral Chronic Sensing Data
Participants whose chronic narrow-band data meet prespecified coverage in both hemispheres
Time frame: From implantation to 3 months after stimulation activation
Number of Protocol Modifications to the Amplitude Schedule
Changes made for clinical safety during the first 3 months after activation
Time frame: From stimulation activation to 3 months after activation
Number of Participants With Adverse Events Related to Study Procedures
Graded with the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Time frame: From consent to 12 months after stimulation activation
Change in Korean Montreal Cognitive Assessment (K-MoCA) Score
Range 0-30; higher scores indicate better cognition
Time frame: Before implantation and 3 and 12 months after stimulation activation
Change in Quality of Life in Epilepsy Inventory-31 (QOLIE-31) Total Score
Range 0-100; higher scores indicate better quality of life
Time frame: Before implantation and 3 and 12 months after stimulation activation
Stimulation-Induced Change in Theta/Alpha/Beta Power
Log ratio ln(ON/OFF) computed as for ΔSG; band limits defined in the statistical analysis plan
Time frame: At stimulation activation, and 1 and 3 months after activation
Stimulation-Induced Change in Aperiodic Exponent/Offset
Difference between ON and OFF in the aperiodic exponent/offset of the parameterized LFP power spectrum
Time frame: At stimulation activation, and 1 and 3 months after activation
Interhemispheric Asymmetry of Anterior Thalamic Spectral Power
Difference between left and right hemispheres in device-recorded spectral power over time
Time frame: From stimulation activation to 12 months after activation
Change in Anterior Thalamic Local Field Potential Power Around Patient-Marked Seizures or Auras
Deviation from the participant's usual narrow-band power around events marked with the patient programmer
Time frame: From stimulation activation to 12 months after activation
Proportion of Participants With at Least 50% Reduction in Seizure Frequency
Months 7-12 compared with baseline
Time frame: Preoperative baseline and months 7-12 after stimulation activation
Percent Reduction in Monthly Seizure Frequency in Months 10-12
Same calculation as the main seizure outcome, using months 10-12
Time frame: Preoperative baseline and months 10-12 after stimulation activation
Percent Reduction in Disabling Seizure Frequency
All disabling seizures recorded in the diary, regardless of corroboration
Time frame: Preoperative baseline and months 7-12 after stimulation activation
Longest Seizure-Free Interval
Longest run of days without a diary-recorded seizure
Time frame: From stimulation activation to 12 months after activation
Plan to share: No — Individual participant data will not be shared outside the study team. The approved consent states that study data will not be provided to third parties.
No publications or documents are linked to this record.
Start is estimated for Nov 2026; primary completion for May 2028, 18 months later.
Of 96 non-industry interventional studies with no phase under Drug Resistant Epilepsy, half reached primary completion within 34 months of starting (the median), counting those still running; a quarter within 20 and three quarters within 75. This study's planned 18 months is below that.
Counting every sponsor, half of 108 studies reached it within 34 months; a quarter within 20 and three quarters within 50.
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From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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