EpilepsyPhase 2Ketamine-sEEGNCT07768618
Electrophysiologic Mechanisms of Ketamine Antidepressant Response
A Phase 2 study testing Ketamine in people with Epilepsy and Depressive Symptoms, run by Emory University at 1 site in United States.
Trial summary
This study aims to identify electrophysiologic biomarkers associated with antidepressant response to ketamine in adults with epilepsy undergoing clinically indicated stereo-electroencephalography (sEEG) monitoring who have at least mild depressive symptoms. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Epilepsy, Depressive Symptoms
- What is being tested?
- Ketamine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2026to Dec 2031
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Admitted to the Emory EMU for clinically indicated sEEG monitoring for epilepsy.
- At least mild depressive symptoms at baseline, defined as MADRS ≥7 or BDI-II ≥14.
- Electrode coverage that includes midline regions sufficient for enrollment and analyses.
- Ability to provide informed consent and to complete bedside tasks/questionnaires in English.
- Expected to remain under inpatient monitoring through the planned ~24-hour post-infusion follow-up unless clinical needs dictate otherwise.
Who cannot join
- Documented IQ <70, intellectual disability, severe cognitive impairment, delirium, severe aphasia, or other condition that prevents valid consent or task participation.
- Current or past schizophrenia-spectrum disorder or other psychotic disorder.
- Current manic/hypomanic episode or bipolar-spectrum illness judged by study psychiatrist/investigator to increase risk or confound interpretation.
- Active alcohol or substance abuse/dependence within the past 3 months.
- Imminent suicide risk or active suicidal intent requiring urgent intervention as determined by clinical assessment. Passive ideation without imminent intent may be considered on a case-by-case basis with psychiatric approval and enhanced monitoring.
- Contraindication to subanesthetic ketamine, including uncontrolled hypertension, unstable cardiovascular disease, aneurysm/vascular malformation or similar condition conferring unacceptable risk, pregnancy, breastfeeding, or other clinically significant medical instability.
- Clinical team determination that ketamine administration or study timing would interfere with epilepsy care or perioperative management.
- Sedative or other medication exposure at a level that, in the judgment of the clinical team, precludes safe ketamine administration or reliable behavioral assessment (participant may be deferred rather than permanently excluded if the issue resolves).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Emory University
Atlanta, Georgia, 30322
Carl Hacker, MD, PhD, 404-778-5770, carl.hacker@emory.edu
Carl Hacker, MD, PhD
About this study
Official title: Electrophysiologic Dynamics of Depression and Antidepressant Response in Epilepsy
This study aims to identify electrophysiologic biomarkers associated with antidepressant response to ketamine in adults with epilepsy undergoing clinically indicated stereo-electroencephalography (sEEG) monitoring who have at least mild depressive symptoms.
Participants will receive a single subanesthetic intravenous ketamine infusion (0.5 mg/kg over 40 minutes) during their Epilepsy Monitoring Unit admission. Intracranial neural recordings and behavioral assessments will be collected before and approximately 24 hours after infusion to examine changes in neural circuits associated with rumination and anhedonia.
Read the detailed description
Depressive symptoms are common among individuals with epilepsy and are associated with reduced quality of life and poorer clinical outcomes. Although neuromodulation therapies have shown promise for treatment-resistant depression, the development of objective biomarkers to guide treatment remains a major challenge. Patients undergoing clinically indicated stereo-electroencephalography (sEEG) monitoring for epilepsy provide a unique opportunity to study human brain circuits with high spatial and temporal resolution.
This prospective, single-site, open-label, within-subject mechanistic clinical trial will enroll adults with epilepsy undergoing inpatient sEEG monitoring who have at least mild depressive symptoms at baseline. Participants will receive a single intravenous ketamine infusion (0.5 mg/kg over 40 minutes) while hospitalized in the Epilepsy Monitoring Unit. Research assessments will be completed before infusion and approximately 24 hours afterward.
The study examines candidate intracranial electrophysiologic measures of prefrontal-posterior midline connectivity and local cortical excitability, drawn from regions implicated in mood-relevant circuits. Behavioral and symptom measures include a task-based measure of thought content and a validated self-report measure of hedonic capacity. Investigators will test whether ketamine-induced neural changes correspond to changes in these behavioral and symptom measures. Additional exploratory analyses will examine whether acute effects during infusion predict delayed responses observed 24 hours later.
All research procedures occur during routine clinical epilepsy monitoring, and no research-driven intracranial stimulation, surgery, imaging, or biospecimen collection is performed.
- Conditions
- Epilepsy, Depressive Symptoms
- Being tested
- Ketamine
- Keywords
- Depression, Epilepsy, Ketamine, Stereo-electroencephalography, Antidepressant Response, Electrophysiologic Biomarker
- Medical subject headings
- Epilepsy, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Participants will receive one subanesthetic intravenous ketamine infusion administered at a dose of 0.5 mg/kg over 40 minutes during admission to the Epilepsy Monitoring Unit. The infusion will be supervised by a psychiatrist experienced in ketamine administration and conducted under continuous clinical monitoring. Intracranial sEEG recordings, behavioral assessments, and symptom measures collected before and approximately 24 hours after infusion will be used to evaluate electrophysiologic biomarkers associated with antidepressant response
| Study group | Role | What they receive |
|---|---|---|
| Intravenous Ketamine During sEEG Monitoring | Experimental | Adults undergoing clinically indicated sEEG monitoring for epilepsy who have at least mild depressive symptoms will receive a single intravenous ketamine infusion (0.5 mg/kg over 40 minutes). Neural, behavioral, and symptom assessments will be performed before and approximately 24 hours after infusion to evaluate electrophysiologic correlates of antidepressant response. Receives: Drug: Ketamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Prefrontal-Posterior Brain Connectivity
This outcome measures intracranial electrophysiologic connectivity between prefrontal and posterior midline brain regions, calculated from gamma-band neural activity.
Measured: Baseline and approximately 24 hours post-ketamine infusion
Change in Prefrontal Cortical Excitability Measure
This outcome measures local cortical excitability using a spectral measure derived from intracranial electrophysiologic recordings in prefrontal brain regions.
Measured: Baseline (pre-infusion) and approximately 24 hours post-ketamine infusion.
Secondary outcomes (4)
Change in Thought Content Task Score
This outcome measures a task-based measure of the emotional content of participants' self-generated thoughts, reflecting positive versus negative thought bias.
Measured: Baseline and approximately 24 hours post-ketamine infusion.
Association Between Change in Prefrontal-Posterior Brain Connectivity and Change in Thought Content Task Score
This outcome evaluates whether change in prefrontal-posterior brain connectivity is associated with change in the thought content task score.
Measured: Baseline and approximately 24 hours post-ketamine infusion.
Change in Hedonic Capacity Score
This outcome measures a validated self-report measure of hedonic capacity, or the ability to experience pleasure.
Measured: Baseline and approximately 24 hours post-ketamine infusion.
Association Between Change in Prefrontal Cortical Excitability and Change in Hedonic Capacity Score
This outcome evaluates whether a change in the prefrontal cortical excitability measure is associated with a change in the hedonic capacity score.
Measured: Baseline and approximately 24 hours post-ketamine infusion.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2026
- Study startDec 2026 (estimated)
- Primary completionDec 2031 (estimated)
- Study completionDec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EpilepsyStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 37 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Principal investigator, Carl Hacker, Emory University
- Investigators
- Carl Hacker, MD, PhD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07768618
- Sponsor's protocol ID
- 2026P000976
- Other IDs
- 1K23MH146912-01
- Acronym
- Ketamine-sEEG
- Status last verified
- Aug 2026
- First submitted
- 12 Aug 2026
- Last updated
- 17 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data shared at study conclusion will include de-identified scientific data underlying the primary findings: intracranial electrophysiology summaries, electrode localization data, behavioral task and symptom-scale data, analysis code, metadata, and documentation needed to validate and replicate the results. Data will be shared through the NIMH Data Archive under controlled access.
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Electrophysiologic Dynamics of Depression and Antidepressant Response in Epilepsy
- ClinicalTrials.gov ID
- NCT07768618
- Acronym / sponsor ID
- Ketamine-sEEG / 2026P000976
- Conditions
- Epilepsy, Depressive Symptoms
- Keywords
- Depression, Epilepsy, Ketamine, Stereo-electroencephalography, Antidepressant Response, Electrophysiologic Biomarker
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 37 participants (estimated)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- Dec 2026 (estimated)
- Primary completion
- Dec 2031 (estimated)
- Study completion
- Dec 2031 (estimated)
- First posted
- 17 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims to identify electrophysiologic biomarkers associated with antidepressant response to ketamine in adults with epilepsy undergoing clinically indicated stereo-electroencephalography (sEEG) monitoring who have at least mild depressive symptoms.
Participants will receive a single subanesthetic intravenous ketamine infusion (0.5 mg/kg over 40 minutes) during their Epilepsy Monitoring Unit admission. Intracranial neural recordings and behavioral assessments will be collected before and approximately 24 hours after infusion to examine changes in neural circuits associated with rumination and anhedonia.
Detailed description
Depressive symptoms are common among individuals with epilepsy and are associated with reduced quality of life and poorer clinical outcomes. Although neuromodulation therapies have shown promise for treatment-resistant depression, the development of objective biomarkers to guide treatment remains a major challenge. Patients undergoing clinically indicated stereo-electroencephalography (sEEG) monitoring for epilepsy provide a unique opportunity to study human brain circuits with high spatial and temporal resolution.
This prospective, single-site, open-label, within-subject mechanistic clinical trial will enroll adults with epilepsy undergoing inpatient sEEG monitoring who have at least mild depressive symptoms at baseline. Participants will receive a single intravenous ketamine infusion (0.5 mg/kg over 40 minutes) while hospitalized in the Epilepsy Monitoring Unit. Research assessments will be completed before infusion and approximately 24 hours afterward.
The study examines candidate intracranial electrophysiologic measures of prefrontal-posterior midline connectivity and local cortical excitability, drawn from regions implicated in mood-relevant circuits. Behavioral and symptom measures include a task-based measure of thought content and a validated self-report measure of hedonic capacity. Investigators will test whether ketamine-induced neural changes correspond to changes in these behavioral and symptom measures. Additional exploratory analyses will examine whether acute effects during infusion predict delayed responses observed 24 hours later.
All research procedures occur during routine clinical epilepsy monitoring, and no research-driven intracranial stimulation, surgery, imaging, or biospecimen collection is performed.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intravenous Ketamine During sEEG Monitoring | Experimental | Drug: KetamineAdults undergoing clinically indicated sEEG monitoring for epilepsy who have at least mild depressive symptoms will receive a single intravenous ketamine infusion (0.5 mg/kg over 40 minutes). Neural, behavioral, and symptom assessments will be performed before and approximately 24 hours after infusion to evaluate electrophysiologic correlates of antidepressant response. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Admitted to the Emory EMU for clinically indicated sEEG monitoring for epilepsy.
- At least mild depressive symptoms at baseline, defined as MADRS ≥7 or BDI-II ≥14.
- Electrode coverage that includes midline regions sufficient for enrollment and analyses.
- Ability to provide informed consent and to complete bedside tasks/questionnaires in English.
- Expected to remain under inpatient monitoring through the planned ~24-hour post-infusion follow-up unless clinical needs dictate otherwise.
Key exclusion criteria (8 listed)
- Documented IQ <70, intellectual disability, severe cognitive impairment, delirium, severe aphasia, or other condition that prevents valid consent or task participation.
- Current or past schizophrenia-spectrum disorder or other psychotic disorder.
- Current manic/hypomanic episode or bipolar-spectrum illness judged by study psychiatrist/investigator to increase risk or confound interpretation.
- Active alcohol or substance abuse/dependence within the past 3 months.
- Imminent suicide risk or active suicidal intent requiring urgent intervention as determined by clinical assessment. Passive ideation without imminent intent may be considered on a case-by-case basis with psychiatric approval and enhanced monitoring.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KetamineParticipants will receive one subanesthetic intravenous ketamine infusion administered at a dose of 0.5 mg/kg over 40 minutes during admission to the Epilepsy Monitoring Unit. The infusion will be supervised by a psychiatrist experienced in ketamine administration and conducted under continuous clinical monitoring. Intracranial sEEG recordings, behavioral assessments, and symptom measures collected before and approximately 24 hours after infusion will be used to evaluate electrophysiologic biomarkers associated with antidepressant response | Drug | Intravenous Ketamine During sEEG Monitoring |
Primary outcome
Change in Prefrontal-Posterior Brain Connectivity
Time frame: Baseline and approximately 24 hours post-ketamine infusion
This outcome measures intracranial electrophysiologic connectivity between prefrontal and posterior midline brain regions, calculated from gamma-band neural activity.
Change in Prefrontal Cortical Excitability Measure
Time frame: Baseline (pre-infusion) and approximately 24 hours post-ketamine infusion.
This outcome measures local cortical excitability using a spectral measure derived from intracranial electrophysiologic recordings in prefrontal brain regions.
4 secondary outcomes
Change in Thought Content Task Score
Time frame: Baseline and approximately 24 hours post-ketamine infusion.
Association Between Change in Prefrontal-Posterior Brain Connectivity and Change in Thought Content Task Score
Time frame: Baseline and approximately 24 hours post-ketamine infusion.
Change in Hedonic Capacity Score
Time frame: Baseline and approximately 24 hours post-ketamine infusion.
Association Between Change in Prefrontal Cortical Excitability and Change in Hedonic Capacity Score
Time frame: Baseline and approximately 24 hours post-ketamine infusion.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2026.
- Individual participant dataSharing planned: Yes. Data shared at study conclusion will include de-identified scientific data underlying the primary findings: intracranial electrophysiology summaries, electrode localization data, behavioral task and symptom-scale data, analysis code, metadata, and documentation needed to validate and replicate the results. Data will be shared through the NIMH Data Archive under controlled access.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Carl Hacker, MD, PhD principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ketamine in people with Epilepsy and Depressive Symptoms, run by Emory University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 17 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Carl Hacker, MD, PhD (404-778-5770, carl.hacker@emory.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Prefrontal-Posterior Brain Connectivity (time frame: Baseline and approximately 24 hours post-ketamine infusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2026.