Major Depressive DisorderNCT05996900
Investigating the Neural Mechanisms of Repetitive Brain Stimulation With Invasive and Noninvasive Electrophysiology in Humans
A study testing Intracranial electrodes and TMS in people with Major Depressive Disorder and Epilepsy, run by Stanford University at 1 site in United States.
Trial summary
Transcranial magnetic stimulation (TMS) is an effective treatment for depression, but clinical outcome is suboptimal, partially because investigators are missing biologically-grounded brain markers which show that TMS is modifying activity at the intended target in the brain. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder, Epilepsy
- What is being tested?
- Intracranial electrodes and TMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 49 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2023to 1 Dec 2027
- Phase
- Interventional
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women, ages 18 to 65
- Medication-refractory epilepsy requiring phase II monitoring
- Must have intellectual capacity to ensure adequate comprehension of the study and potential risks involved in order to provide informed consent
- No current or history of major neurological disorders other than epilepsy
Who cannot join
- Those with a contraindication for MRIs (e.g. implanted metal)
- Any unstable medical condition
- Neurological or uncontrolled medical disease
- Active substance abuse
- Currently pregnant or breastfeeding
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, 1 recruiting
- Recruiting
Stanford University
Stanford, California, 94305
Jade Truong, kellerlab@stanford.edu
About this study
Transcranial magnetic stimulation (TMS) is an effective treatment for depression, but clinical outcome is suboptimal, partially because investigators are missing biologically-grounded brain markers which show that TMS is modifying activity at the intended target in the brain. The goal of this proposal is to characterize the key markers of the brain's response to repeated doses of TMS with high resolution using invasive brain recordings in humans, and relate these brain markers to noninvasive recordings. These markers will improve the understanding of TMS and can be used to optimize and enhance clinical efficacy for depression and other psychiatric disorders.
Read the detailed description
Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder, but remission rates are 20-40%, and ideal stimulation parameters are unknown. rTMS is thought to work by changing the synaptic strength of neurons. The ability of the brain to make these changes is referred to as plasticity. rTMS-induced changes are thought to build with successive treatment sessions, a process referred to as metaplasticity. While both plasticity and metaplasticity are well-established in single cell physiology, relevance to rTMS in humans remains unknown. To improve clinical efficacy, the investigators need to understand 1) the neural response to a single rTMS session (plasticity), 2) the neural response to repeated daily rTMS sessions (metaplasticity), and 3) whether computational models of plasticity based on single-cell physiology apply to human patients receiving rTMS for depression.
Goals of the study are to 1) establish a detailed mechanistic understanding of the brain changes during current rTMS treatment; 2) identify clinically meaningful electrophysiological biomarkers for rTMS treatment; 3) establish a computational model to help predict both brain and clinical changes.
- Conditions
- Major Depressive Disorder, Epilepsy
- Being tested
- Intracranial electrodes, TMS
- Medical subject headings
- Depressive Disorder, Major, Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intracranial electrodesDevice
Intracranial electrodes will be used for the delivery of invasive brain stimulation.
TMSDevice
TMS will be used for the delivery of noninvasive brain stimulation both before and after implantation electrode surgery.
| Study group | Role | What they receive |
|---|---|---|
| TBS via direct electrical stimulation | Active comparator | Not described Receives: Device: Intracranial electrodes |
| TBS via transcranial magnetic stimulation | Active comparator | Not described Receives: Device: TMS |
| Sham TBS via direct electrical stimulation | Sham comparator | Not described Receives: Device: Intracranial electrodes |
| Sham TBS via transcranial magnetic stimulation | Sham comparator | Not described Receives: Device: TMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
TMS-iEEG change after one TBS session
Change in evoked response measured after a single TBS session for active and sham, by resting state iEEG (intracranial EEG) and/or sEEG (stereo EEG).
Measured: 45 minutes
Secondary outcomes (3)
ES-iEEG change after one TBS session
Change in evoked response measured after a single TBS session for active and sham, by resting state iEEG and/or sEEG.
Measured: 45 minutes
ES-iEEG change between two sequential TBS sessions
Change in single-pulse evoked response, or cortico-cortical evoked potentials (CCEPs), measured between two sequential TBS sessions, by resting state iEEG and/or sEEG.
Measured: 45 minutes
TMS-iEEG change between two sequential TBS sessions
Change in single-pulse evoked response, or cortico-cortical evoked potentials (CCEPs), measured between two sequential TBS sessions, by resting state iEEG and/or sEEG.
Measured: 45 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2023
- Study start1 Sep 2023
- Primary completion1 Oct 2027 (estimated)
- Study completion1 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Stanford 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 49 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Iowa, Massachusetts General Hospital, National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Corey Keller, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05996900
- Sponsor's protocol ID
- 11354-1
- Other IDs
- 1R01MH132074
- Status last verified
- Mar 2026
- First submitted
- 18 Jul 2023
- Last updated
- 12 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating the Neural Mechanisms of Repetitive Brain Stimulation With Invasive and Noninvasive Electrophysiology in Humans
- ClinicalTrials.gov ID
- NCT05996900
- Acronym / sponsor ID
- 11354-1
- Conditions
- Major Depressive Disorder, Epilepsy
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 49 participants (estimated)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- University of Iowa, Massachusetts General Hospital, National Institute of Mental Health (NIMH)
- Study start
- 1 Sep 2023 (actual)
- Primary completion
- 1 Oct 2027 (estimated)
- Study completion
- 1 Dec 2027 (estimated)
- First posted
- 18 Aug 2023 (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.
Transcranial magnetic stimulation (TMS) is an effective treatment for depression, but clinical outcome is suboptimal, partially because investigators are missing biologically-grounded brain markers which show that TMS is modifying activity at the intended target in the brain. The goal of this proposal is to characterize the key markers of the brain's response to repeated doses of TMS with high resolution using invasive brain recordings in humans, and relate these brain markers to noninvasive recordings. These markers will improve the understanding of TMS and can be used to optimize and enhance clinical efficacy for depression and other psychiatric disorders.
Detailed description
Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder, but remission rates are 20-40%, and ideal stimulation parameters are unknown. rTMS is thought to work by changing the synaptic strength of neurons. The ability of the brain to make these changes is referred to as plasticity. rTMS-induced changes are thought to build with successive treatment sessions, a process referred to as metaplasticity. While both plasticity and metaplasticity are well-established in single cell physiology, relevance to rTMS in humans remains unknown. To improve clinical efficacy, the investigators need to understand 1) the neural response to a single rTMS session (plasticity), 2) the neural response to repeated daily rTMS sessions (metaplasticity), and 3) whether computational models of plasticity based on single-cell physiology apply to human patients receiving rTMS for depression.
Goals of the study are to 1) establish a detailed mechanistic understanding of the brain changes during current rTMS treatment; 2) identify clinically meaningful electrophysiological biomarkers for rTMS treatment; 3) establish a computational model to help predict both brain and clinical changes.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| TBS via direct electrical stimulation | Active comparator | Device: Intracranial electrodes |
| TBS via transcranial magnetic stimulation | Active comparator | Device: TMS |
| Sham TBS via direct electrical stimulation | Sham comparator | Device: Intracranial electrodes |
| Sham TBS via transcranial magnetic stimulation | Sham comparator | Device: TMS |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Men and women, ages 18 to 65
- Medication-refractory epilepsy requiring phase II monitoring
- Must have intellectual capacity to ensure adequate comprehension of the study and potential risks involved in order to provide informed consent
- No current or history of major neurological disorders other than epilepsy
Key exclusion criteria (5 listed)
- Those with a contraindication for MRIs (e.g. implanted metal)
- Any unstable medical condition
- Neurological or uncontrolled medical disease
- Active substance abuse
- Currently pregnant or breastfeeding
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 |
|---|---|---|
| Intracranial electrodesIntracranial electrodes will be used for the delivery of invasive brain stimulation. | Device | Sham TBS via direct electrical stimulation, TBS via direct electrical stimulation |
| TMSTMS will be used for the delivery of noninvasive brain stimulation both before and after implantation electrode surgery. | Device | Sham TBS via transcranial magnetic stimulation, TBS via transcranial magnetic stimulation |
Primary outcome
TMS-iEEG change after one TBS session
Time frame: 45 minutes
Change in evoked response measured after a single TBS session for active and sham, by resting state iEEG (intracranial EEG) and/or sEEG (stereo EEG).
3 secondary outcomes
ES-iEEG change after one TBS session
Time frame: 45 minutes
ES-iEEG change between two sequential TBS sessions
Time frame: 45 minutes
TMS-iEEG change between two sequential TBS sessions
Time frame: 45 minutes
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 12 Mar 2026.
Related trials for Major Depressive Disorder
Not yet recruiting
Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
Adverse Childhood Experience, Depression / Major Depressive Disorder
RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
Recruiting
Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics
Major Depressive Disorder, Apathy
RecruitingObservational study
Student Precarity and Psychiatry
Depressive Disorder, Major, Generalized Anxiety Disorder
Not yet recruiting
Acute Intermittent Hypoxia Therapy for Depression
Major Depressive Disorder (MDD)
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intracranial electrodes and TMS in people with Major Depressive Disorder and Epilepsy, run by Stanford 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 4 inclusion and 5 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: looking for participants now, as of the sponsor's last update on 12 Mar 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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 Jade Truong ((408) 840-3313, kellerlab@stanford.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
TMS-iEEG change after one TBS session (time frame: 45 minutes). 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 12 Mar 2026.