DepressionNCT04663841
Neural Circuit Biomarkers of Transcranial Magnetic Stimulation Study
An observational study of Depression, run by Stanford University at 1 site in United States.
Trial summary
This study is currently recruiting Veterans only. The objective of this observational study is to test whether neuroimaging biomarkers of repetitive transcranial magnetic stimulation (TMS) can be prospectively replicated in a large ecologically valid sample. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Depression
- What is being tested?
- transcranial magnetic stimulation
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Nov 2020to 31 May 2026
- Phase
- Observational
- 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
Study population: Veterans with pharmacoresistant major depressive disorder (MDD) participating in the VA Clinical TMS Program. Given the complex nature of the veteran sample, the primary diagnosis of MDD may be comorbid with other disorders, including post-traumatic stress disorder (PTSD).
Who may be able to join
- Ages 18 years and older
- Meets Diagnostic and Statistical Manual edition 5 (DSM-5) criteria for Major Depressive Disorder (MDD) (as documented by the treating physician)
- Meet study criteria for pharmacoresistance in accordance with the Clinical transcranial magnetic stimulation (TMS) Program (i.e. failed at least one antidepressant in the current episode)
- Ability to obtain a motor threshold (MT) prior to the start of treatment
- Stable medical conditions and ability to maintain stability on current medication regimen for the duration of treatment
- Ability to participate in a daily treatment regimen
- Able to read, verbalize understanding, and voluntarily sign the Informed Consent Form prior to participating in any study-specific procedures or assessments
Who cannot join
- History of seizure disorder
- Structural or neurologic abnormalities present or in close proximity to the treatment site
- History of brain surgery
- Pacemaker or medical infusion device (unless magnetic resonance imaging compatible)
- History of traumatic brain injury within 60 days of the start of treatment
- Severe or uncontrolled alcohol or substance use disorders
Show all 14Show fewer
- Active withdrawal from alcohol or substances
- Implanted device in the head
- Metal in the head
- Severe impediment to vision, hearing and/or hand movement, likely to interfere with ability to complete the assessments, or unable and/or unlikely to follow the study protocols
- Lifetime history of bipolar I disorder
- Inability to speak, read or understand English
- Plans to move out of the area during the study period
- Clinician and/or Investigator discretion for clinical safety or protocol adherence
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University Department of Psychiatry
Stanford, California, 94305
About this study
Official title: Mechanistic Circuit Markers of Transcranial Magnetic Stimulation Outcomes in Pharmacoresistant Depression
This study is currently recruiting Veterans only. The objective of this observational study is to test whether neuroimaging biomarkers of repetitive transcranial magnetic stimulation (TMS) can be prospectively replicated in a large ecologically valid sample. We focus on cognitive network connectivity as a predictive biomarker of the clinical effect of TMS, and as a response biomarker of change with TMS. We address this objective through a pragmatic approach in which we recruit patients undergoing routine clinical care and program evaluation in a Veterans Administration multi-site clinical TMS program.
Read the detailed description
Although repetitive transcranial magnetic stimulation (TMS) is becoming a gold standard treatment for pharmacoresistant depression, we lack neural target biomarkers for identifying who is most likely to respond to TMS and why. To address this gap in knowledge this observational study evaluates neural targets defined by activation and functional connectivity of the dorsolateral prefrontal cortex-anchored cognitive control circuit, regions of the default mode network and attention circuit, and interactions with the subgenual anterior cingulate.
The study evaluates whether these targets and interactions between them change in a dose-dependent manner, whether changes in these neural targets correspond to changes in cognitive behavioral performance, and whether baseline and early change in neural target and cognitive behavioral performance predict subsequent symptom severity, suicidality, and quality of life outcomes.
This study is designed as a pragmatic, mechanistic observational trial partnering with the National Clinical TMS Program of the Veteran's Health Administration.
All veterans will receive a clinical course of TMS as part of their routine care. Those who agree to enrollment in the observational study will be assessed at 'baseline' prior to commencement of their TMS treatment, 'first week' after initiation of TMS (targeting five sessions) and 'post-treatment' at the completion of TMS (targeting 30 sessions).
Veterans will be assessed using functional magnetic resonance imaging (fMRI), a cognitive behavioral performance battery, and established questionnaires.
To our knowledge, our study will be the first pragmatic, mechanistic observational trial to use fMRI imaging and cognitive-behavioral performance as biomarkers of TMS treatment response in pharmacoresistant MDD.
- Conditions
- Depression
- Being tested
- transcranial magnetic stimulation
- Keywords
- treatment resistant depression
- Medical subject headings
- Depression, Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
transcranial magnetic stimulationOther
Also called TMS; repetitive transcranial magnetic stimulation
transcranial magnetic stimulation is delivered as part of routine care and is not managed by this observational study
What is being measured
The primary outcome is the main question the study is designed to answer.
Go-NoGo elicited neural circuit function
Activation and connectivity assessed using functional magnetic resonance imaging during a GoNoGo task
Measured: Baseline
Go-NoGo elicited neural circuit function
Activation and connectivity assessed using functional magnetic resonance imaging during a GoNoGo task
Measured: Up to 2 weeks
Go-NoGo elicited neural circuit function
Activation and connectivity assessed using functional magnetic resonance imaging during a GoNoGo task
Measured: Up to 8 weeks
N-Back elicited neural circuit function
Activation and connectivity assessed using functional magnetic resonance imaging during an N-Back task
Measured: Baseline
N-Back elicited neural circuit function
Activation and connectivity assessed using functional magnetic resonance imaging during an N-Back task
Measured: Up to 2 weeks
N-Back elicited neural circuit function
Activation and connectivity assessed using functional magnetic resonance imaging during an N-Back task
Measured: Up to 8 weeks
Resting state neural circuit function
connectivity assessed using functional magnetic resonance imaging during a resting condition
Measured: Baseline
Resting state neural circuit function
connectivity assessed using functional magnetic resonance imaging during a resting condition
Measured: Up to 2 weeks
Resting state neural circuit function
connectivity assessed using functional magnetic resonance imaging during a resting condition
Measured: Up to 8 weeks
Secondary outcomes (21)
Symbol Digit Coding Test
Cognitive-Behavioral Performance accuracy on the Symbol Digit Coding Test
Measured: Baseline
Symbol Digit Coding Test
Cognitive-Behavioral Performance accuracy on the Symbol Digit Coding Test
Measured: Up to 2 weeks
Symbol Digit Coding Test
Cognitive-Behavioral Performance accuracy on the Symbol Digit Coding Test
Measured: Up to 8 weeks
Stroop Test
Cognitive-Behavioral Performance accuracy and reaction time on the Stroop Test
Measured: Baseline
Stroop Test
Cognitive-Behavioral Performance accuracy and reaction time on the Stroop Test
Measured: Up to 2 weeks
Stroop Test
Cognitive-Behavioral Performance accuracy and reaction time on the Stroop Test
Measured: Up to 8 weeks
Shifting Attention Test
Cognitive-Behavioral Performance accuracy and reaction time on the Shifting Attention Test
Measured: Baseline
Shifting Attention Test
Cognitive-Behavioral Performance accuracy and reaction time on the Shifting Attention Test
Measured: Up to 2 weeks
Shifting Attention Test
Cognitive-Behavioral Performance accuracy and reaction time on the Shifting Attention Test
Measured: Up to 8 weeks
Continuous Performance Test
Cognitive-Behavioral Performance accuracy and reaction time on the Continuous Performance Test platform
Measured: Baseline
Continuous Performance Test
Cognitive-Behavioral Performance accuracy and reaction time on the Continuous Performance Test platform
Measured: Up to 2 weeks
Continuous Performance Test
Cognitive-Behavioral Performance accuracy and reaction time on the Continuous Performance Test platform
Measured: Up to 8 weeks
Depressive Symptoms
Clinical outcome assessed using the Quick Inventory of Depressive Symptoms (QIDS)- Self Report Form. The total score ranges from 0 to 27 with higher scores indicating greater severity.
Measured: Baseline
Depressive Symptoms
Clinical outcome assessed using the Quick Inventory of Depressive Symptoms (QIDS)- Self Report Form. The total score ranges from 0 to 27 with higher scores indicating greater severity.
Measured: Up to 2 weeks
Depressive Symptoms
Clinical outcome assessed using the Quick Inventory of Depressive Symptoms (QIDS)- Self Report Form. The total score ranges from 0 to 27 with higher scores indicating greater severity.
Measured: Up to 8 weeks
Daily function related to quality of life
Clinical outcome assessed using the Veterans' RAND 36-item Health Survey (VR-36). All questions are scored on a scale from 0 to 100, with 100 representing the highest level of functioning possible.
Measured: Baseline
Daily function related to quality of life
Clinical outcome assessed using the Veterans' RAND 36-item Health Survey (VR-36). All questions are scored on a scale from 0 to 100, with 100 representing the highest level of functioning possible.
Measured: Up to 2 weeks
Daily function related to quality of life
Clinical outcome assessed using the Veterans' RAND 36-item Health Survey (VR-36). All questions are scored on a scale from 0 to 100, with 100 representing the highest level of functioning possible.
Measured: Up to 8 weeks
Suicidal ideation
Columbia-Suicide Severity Rating Scale (C-SSRS). The total score ranges from 2 to 25, with a higher number indicating more intense ideation and greater risk.
Measured: Baseline
Suicidal ideation
Columbia-Suicide Severity Rating Scale (C-SSRS). The total score ranges from 2 to 25, with a higher number indicating more intense ideation and greater risk.
Measured: Up to 2 weeks
Suicidal ideation
Columbia-Suicide Severity Rating Scale (C-SSRS). The total score ranges from 2 to 25, with a higher number indicating more intense ideation and greater risk.
Measured: Up to 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2020
- Study start2 Nov 2020
- Primary completion31 May 2026 (estimated)
- Study completion31 May 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DepressionStudies 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
- Observational
- Observational model
- Case only
- Time perspective
- Other
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- VA Palo Alto Health Care System, Florida State University, University of South Florida, Medical University of South Carolina, University of Minnesota, Minneapolis Veterans Affairs Medical Center, Brown University, Providence VA Medical Center, Dartmouth College, Dartmouth-Hitchcock Medical Center, White River Junction VA Medical Center
- Responsible party
- Principal investigator, Leanne Williams, Stanford University
- Investigators
- Leanne Williams, PhD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04663841
- Sponsor's protocol ID
- 52695
- Status last verified
- Dec 2025
- First submitted
- 27 Nov 2020
- Last updated
- 5 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanistic Circuit Markers of Transcranial Magnetic Stimulation Outcomes in Pharmacoresistant Depression
- ClinicalTrials.gov ID
- NCT04663841
- Acronym / sponsor ID
- 52695
- Conditions
- Depression
- Keywords
- treatment resistant depression
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- VA Palo Alto Health Care System, Florida State University, University of South Florida, Medical University of South Carolina, University of Minnesota, Minneapolis Veterans Affairs Medical Center, Brown University, Providence VA Medical Center, Dartmouth College, Dartmouth-Hitchcock Medical Center, White River Junction VA Medical Center
- Study start
- 2 Nov 2020 (actual)
- Primary completion
- 31 May 2026 (estimated)
- Study completion
- 31 May 2026 (estimated)
- First posted
- 11 Dec 2020 (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 is currently recruiting Veterans only. The objective of this observational study is to test whether neuroimaging biomarkers of repetitive transcranial magnetic stimulation (TMS) can be prospectively replicated in a large ecologically valid sample. We focus on cognitive network connectivity as a predictive biomarker of the clinical effect of TMS, and as a response biomarker of change with TMS. We address this objective through a pragmatic approach in which we recruit patients undergoing routine clinical care and program evaluation in a Veterans Administration multi-site clinical TMS program.
Detailed description
Although repetitive transcranial magnetic stimulation (TMS) is becoming a gold standard treatment for pharmacoresistant depression, we lack neural target biomarkers for identifying who is most likely to respond to TMS and why. To address this gap in knowledge this observational study evaluates neural targets defined by activation and functional connectivity of the dorsolateral prefrontal cortex-anchored cognitive control circuit, regions of the default mode network and attention circuit, and interactions with the subgenual anterior cingulate.
The study evaluates whether these targets and interactions between them change in a dose-dependent manner, whether changes in these neural targets correspond to changes in cognitive behavioral performance, and whether baseline and early change in neural target and cognitive behavioral performance predict subsequent symptom severity, suicidality, and quality of life outcomes.
This study is designed as a pragmatic, mechanistic observational trial partnering with the National Clinical TMS Program of the Veteran's Health Administration.
All veterans will receive a clinical course of TMS as part of their routine care. Those who agree to enrollment in the observational study will be assessed at 'baseline' prior to commencement of their TMS treatment, 'first week' after initiation of TMS (targeting five sessions) and 'post-treatment' at the completion of TMS (targeting 30 sessions).
Veterans will be assessed using functional magnetic resonance imaging (fMRI), a cognitive behavioral performance battery, and established questionnaires.
To our knowledge, our study will be the first pragmatic, mechanistic observational trial to use fMRI imaging and cognitive-behavioral performance as biomarkers of TMS treatment response in pharmacoresistant MDD.
Study design
- Observational model
- Case only
- Time perspective
- Other
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Veterans with pharmacoresistant major depressive disorder (MDD) participating in the VA Clinical TMS Program. Given the complex nature of the veteran sample, the primary diagnosis of MDD may be comorbid with other disorders, including post-traumatic stress disorder (PTSD).
Key inclusion criteria (7 listed)
- Ages 18 years and older
- Meets Diagnostic and Statistical Manual edition 5 (DSM-5) criteria for Major Depressive Disorder (MDD) (as documented by the treating physician)
- Meet study criteria for pharmacoresistance in accordance with the Clinical transcranial magnetic stimulation (TMS) Program (i.e. failed at least one antidepressant in the current episode)
- Ability to obtain a motor threshold (MT) prior to the start of treatment
- Stable medical conditions and ability to maintain stability on current medication regimen for the duration of treatment
Key exclusion criteria (14 listed)
- History of seizure disorder
- Structural or neurologic abnormalities present or in close proximity to the treatment site
- History of brain surgery
- Pacemaker or medical infusion device (unless magnetic resonance imaging compatible)
- History of traumatic brain injury within 60 days of the start of treatment
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 |
|---|---|---|
| transcranial magnetic stimulationAlso: TMS; repetitive transcranial magnetic stimulationtranscranial magnetic stimulation is delivered as part of routine care and is not managed by this observational study | Other | – |
Primary outcome
Go-NoGo elicited neural circuit function
Time frame: Baseline
Activation and connectivity assessed using functional magnetic resonance imaging during a GoNoGo task
Go-NoGo elicited neural circuit function
Time frame: Up to 2 weeks
Activation and connectivity assessed using functional magnetic resonance imaging during a GoNoGo task
Go-NoGo elicited neural circuit function
Time frame: Up to 8 weeks
Activation and connectivity assessed using functional magnetic resonance imaging during a GoNoGo task
N-Back elicited neural circuit function
Time frame: Baseline
Activation and connectivity assessed using functional magnetic resonance imaging during an N-Back task
N-Back elicited neural circuit function
Time frame: Up to 2 weeks
Activation and connectivity assessed using functional magnetic resonance imaging during an N-Back task
N-Back elicited neural circuit function
Time frame: Up to 8 weeks
Activation and connectivity assessed using functional magnetic resonance imaging during an N-Back task
Resting state neural circuit function
Time frame: Baseline
connectivity assessed using functional magnetic resonance imaging during a resting condition
Resting state neural circuit function
Time frame: Up to 2 weeks
connectivity assessed using functional magnetic resonance imaging during a resting condition
Resting state neural circuit function
Time frame: Up to 8 weeks
connectivity assessed using functional magnetic resonance imaging during a resting condition
21 secondary outcomes
Symbol Digit Coding Test
Time frame: Baseline
Symbol Digit Coding Test
Time frame: Up to 2 weeks
Symbol Digit Coding Test
Time frame: Up to 8 weeks
Stroop Test
Time frame: Baseline
Stroop Test
Time frame: Up to 2 weeks
Stroop Test
Time frame: Up to 8 weeks
Shifting Attention Test
Time frame: Baseline
Shifting Attention Test
Time frame: Up to 2 weeks
Shifting Attention Test
Time frame: Up to 8 weeks
Continuous Performance Test
Time frame: Baseline
Continuous Performance Test
Time frame: Up to 2 weeks
Continuous Performance Test
Time frame: Up to 8 weeks
Depressive Symptoms
Time frame: Baseline
Depressive Symptoms
Time frame: Up to 2 weeks
Depressive Symptoms
Time frame: Up to 8 weeks
Daily function related to quality of life
Time frame: Baseline
Daily function related to quality of life
Time frame: Up to 2 weeks
Daily function related to quality of life
Time frame: Up to 8 weeks
Suicidal ideation
Time frame: Baseline
Suicidal ideation
Time frame: Up to 2 weeks
Suicidal ideation
Time frame: Up to 8 weeks
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 5 Jan 2026.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Leanne Williams, PhD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Depression, 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 7 inclusion and 14 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: under way, not looking for participants, as of the sponsor's last update on 5 Jan 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.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Go-NoGo elicited neural circuit function (time frame: Baseline). The study lists 9 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 5 Jan 2026.