Depressive Disorder, MajorSUNSETNCT04581902
Biomarkers of Depression and Treatment Response
A study testing rTMS therapy in people with Depressive Disorder, Major, run by University of California, San Francisco at 1 site in United States.
Trial summary
This study is a stratified, parallel-group, single-center study utilizing multimodal imaging techniques to identify biomarkers for Major Depressive Disorder (MDD). The study goal is to identify biomarkers for MDD and treatment response that can be implemented in clinical diagnosis and care as valid and reliable… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Depressive Disorder, Major
- What is being tested?
- rTMS therapy
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2020to Sep 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-70
- Meet Diagnostic and Statistical Manual-V (DSM-V) diagnostic criteria for Major Depressive Disorder in a current major depressive episode, without psychotic features.
- Has Montgomery-Asberg Depressive Rating Scale (MADRS) of > 19 at baseline, corresponding with moderate to severe depression.
- Demonstrate a moderate level of resistance to antidepressant treatment in the current episode, defined as a failure of 1-4 adequate medication trials.
- If participant is on a regimen of psychotropic medication, no changes in this regimen should be made during the period between the time at which pre-treatment and post-treatment scans are taken.
- Willing and able to undergo non-invasive brain stimulation
Show all 9Show fewer
- Willing and able to attend research visits for approximately 8 weeks
- Willing and able to provide informed consent
- Ability to speak and read English
Who cannot join
- Diagnosed with acute or chronic psychotic symptoms of disorders (e.g. schizophrenia, schizophreniform, schizoaffective disorder) in the current depressive episode.
- Has neurological conditions including epilepsy, cerebrovascular disease, dementia, increased intracranial pressure, having a history of repetitive or severe head trauma, or with primary or secondary tumors in the central nervous system.
- Presence of an implanted magnetic-sensitive medical device in or near the head, including but not limited to pacemaker, vagus nerve stimulator, or metal aneurysm clips or coils, staples, or stents.
- Generalized anxiety disorder as the primary DSM-V disorder during the current MDD episode.
- Meets criteria for alcohol or substance abuse or dependence (other than caffeine) in previous 6 months, as determined by the SCID
- History of seizures
Show all 12Show fewer
- Implantable hardware not compatible with MRI or with the study
- Inability to comply with study daily visits
- Women who are pregnant, plan to become pregnant, or breast feeding
- Inability to speak and/or read English
- Inability to give consent
- Any active suicidal intent or plan during the current depressive episode, as determined by a score of 3 on Question #9 of Beck's Depression Inventory (scores reviewed daily by study team members versed in scoring clinical scales), or as by a subjective determination by a study clinician during any study visit.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Rebecca Martinez, MS contact
United States1 site, 1 recruiting
- Recruiting
University of California, San Francisco
San Francisco, California, 94143
Katherine Scangos, MD, PhD, 415-476-7439, trdepression@ucsf.edu
Rebecca Martinez, MS, 415- 514-6489, rebecca.martinez@ucsf.edu
About this study
This study is a stratified, parallel-group, single-center study utilizing multimodal imaging techniques to identify biomarkers for Major Depressive Disorder (MDD). The study goal is to identify biomarkers for MDD and treatment response that can be implemented in clinical diagnosis and care as valid and reliable measures, through monitoring neurophysiological and electrophysiological changes across the course of transcranial magnetic stimulation (TMS) treatment.
Read the detailed description
First, the study will examine the replicability and prognostic utility of two previously identified potential biomarkers for MDD using resting state imaging. Second, investigators will conduct an exploratory, whole brain analysis combining EEG and imaging techniques to identify new potential biomarkers for MDD and treatment response as participants complete a course of TMS treatment. It is the hope to shed new light on the mechanisms underlying depression and relapse, which may allow for a more effective, personalized selection of treatment course.
Participants will complete initial screening and baseline evaluation, along with resting-state functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI) and electroencephalography (EEG) scans prior to the initial TMS treatment. Participants will complete 30-36 TMS sessions and a post-treatment evaluation, along with mid- and post-treatment fMRI, DTI and EEG scans.
It is anticipated that participants with MDD have a specific set of neural features that can classify with high precision patients with MDD from those who do not, and that align with clinical diagnoses. This set of neural features will change across the course of treatment. Further, investigators expect that improvement as rated by a common MDD measure is modulated by time of treatment.
- Conditions
- Depressive Disorder, Major
- Being tested
- rTMS therapy
- Keywords
- transcranial magnetic stimulation, depression, biomarker, TMS, neuroimaging, rTMS
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rTMS therapyDevice
Also called repetitive TMS, repetitive transcranial magnetic stimulation
rTMS treatment parameters will be determined by TMS care providers. Typical TMS settings for MDD involve rTMS applied at 10 Hz with an intensity of 120 % of resting motor threshold. Forty trains of 4 s duration with 11s of trains is typically applied (3000 pulses per day), resulting in approximately 90,000 pulses in a given treatment course.
| Study group | Role | What they receive |
|---|---|---|
| Morning rTMS treatment | Experimental | Eligible participants will be assigned to the afternoon treatment group. Prior to the onset of rTMS treatment, EEG scans and magnetic resonance imaging (MRI) sessions including diffusion weighted imaging will be recorded as baseline measures. These measures will also be repeated at treatment midpoint and within one month of rTMS discontinuation in order to track structural and functional changes that occur over the course of treatment. Participants will complete an initial screening followed by 30-40 daily sessions of repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex (DLPFC), completed with their TMS provider. Receives: Device: rTMS therapy |
| Afternoon rTMS treatment | Experimental | Eligible participants will be assigned to the afternoon treatment group. Prior to the onset of rTMS treatment, EEG scans and magnetic resonance imaging (MRI) sessions including diffusion weighted imaging will be recorded as baseline measures. These measures will also be repeated at treatment midpoint and within one month of rTMS discontinuation in order to track structural and functional changes that occur over the course of treatment. Participants will complete an initial screening followed by 30-40 daily sessions of repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex (DLPFC), completed with their TMS provider. Receives: Device: rTMS therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in MADRS score from baseline to end of treatment
Effect size of active stimulation (mean difference in Montgomery Asberg Depression Rating Scale (MADRS) score) before and after morning and afternoon treatment course. Higher MADRS score indicates more severe depression; the overall score ranges from 0 to 60.
Measured: Up to one month prior to initial TMS session (baseline) to within one month following the completion of TMS treatment (~ 8 weeks)
Change in resting state BOLD signal from baseline to end of treatment
Change in resting state functional magnetic resonance imaging BOLD signal before and after the active treatment period.
Measured: Up to one month prior to initial TMS session (baseline) to within one month following the completion of TMS treatment (~ 8 weeks)
Change in resting state EEG from baseline to end of treatment
Change in resting state EEG (electroencephalogram) alpha band coherence before and after the active treatment period.
Measured: Up to one month prior to initial TMS session (baseline) to within one month following the completion of TMS treatment (~ 8 weeks)
Change in white matter integrity from baseline to end of treatment
Change in white matter integrity as measured by diffusion tensor imaging (DTI) before and after the active treatment period.
Measured: Up to one month prior to initial TMS session (baseline) to within one month following the completion of TMS treatment (~ 8 weeks)
Secondary outcomes (4)
Change in Beck's Depression Inventory (BDI) score from baseline to end of treatment
The difference in Beck's Depression Inventory (BDI) score after TMS treatment course.Higher BDI score indicates more severe depression; the overall score ranges from 0 to 63.
Measured: Up to one month prior to initial TMS session (baseline) to within one month following the completion of TMS treatment (~ 8 weeks)
Change in Patient Health Questionnaire (PHQ9) score from baseline to end of treatment
The difference in Patient Health Questionnaire (PHQ9) score after TMS treatment course. Higher PHQ9 score indicates more severe depression; the overall score ranges from 0 to 27.
Measured: Up to one month prior to initial TMS session (baseline) to within one month following the completion of TMS treatment (~ 8 weeks)
Change in Generalized Anxiety Disorder (GAD-7) score from baseline to end of treatment
The difference in Generalized Anxiety Disorder (GAD-7) score after TMS treatment course. Higher GAD7 score indicates more severe depression; the overall score ranges from 0 to 21.
Measured: Up to one month prior to initial TMS session (baseline) to within one month following the completion of TMS treatment (~ 8 weeks)
Change in Inventory of Depressive Symptomatology (IDS-30 self report) score from baseline to end of treatment.
The difference in Inventory of Depressive Symptomatology Self-Report (IDS-SR) score after TMS treatment course. Higher IDS score indicates more severe depression; the overall score ranges from 0 to 84.
Measured: Up to one month prior to initial TMS session (baseline) to within one month following the completion of TMS treatment (~ 8 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2020
- Study start1 Dec 2020
- Primary completionSep 2027 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Depressive Disorder, MajorStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe 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
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- This will be a parallel-groups, stratified interventional study to investigate methods of optimizing clinical care in patients diagnosed with MDD.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Andrew Krystal, MD, MS, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04581902
- Sponsor's protocol ID
- 19-28340
- Acronym
- SUNSET
- Status last verified
- Jan 2026
- First submitted
- 27 Jul 2020
- Last updated
- 30 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biomarkers of Depression and Treatment Response
- ClinicalTrials.gov ID
- NCT04581902
- Acronym / sponsor ID
- SUNSET / 19-28340
- Conditions
- Depressive Disorder, Major
- Keywords
- transcranial magnetic stimulation, depression, biomarker, TMS, neuroimaging, rTMS
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Study start
- 1 Dec 2020 (actual)
- Primary completion
- Sep 2027 (estimated)
- Study completion
- Sep 2027 (estimated)
- First posted
- 9 Oct 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 a stratified, parallel-group, single-center study utilizing multimodal imaging techniques to identify biomarkers for Major Depressive Disorder (MDD). The study goal is to identify biomarkers for MDD and treatment response that can be implemented in clinical diagnosis and care as valid and reliable measures, through monitoring neurophysiological and electrophysiological changes across the course of transcranial magnetic stimulation (TMS) treatment.
Detailed description
First, the study will examine the replicability and prognostic utility of two previously identified potential biomarkers for MDD using resting state imaging. Second, investigators will conduct an exploratory, whole brain analysis combining EEG and imaging techniques to identify new potential biomarkers for MDD and treatment response as participants complete a course of TMS treatment. It is the hope to shed new light on the mechanisms underlying depression and relapse, which may allow for a more effective, personalized selection of treatment course.
Participants will complete initial screening and baseline evaluation, along with resting-state functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI) and electroencephalography (EEG) scans prior to the initial TMS treatment. Participants will complete 30-36 TMS sessions and a post-treatment evaluation, along with mid- and post-treatment fMRI, DTI and EEG scans.
It is anticipated that participants with MDD have a specific set of neural features that can classify with high precision patients with MDD from those who do not, and that align with clinical diagnoses. This set of neural features will change across the course of treatment. Further, investigators expect that improvement as rated by a common MDD measure is modulated by time of treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- This will be a parallel-groups, stratified interventional study to investigate methods of optimizing clinical care in patients diagnosed with MDD.
| Arm | Type | Receives |
|---|---|---|
| Morning rTMS treatment | Experimental | Device: rTMS therapyEligible participants will be assigned to the afternoon treatment group. Prior to the onset of rTMS treatment, EEG scans and magnetic resonance imaging (MRI) sessions including diffusion weighted imaging will be recorded as baseline measures. These measures will also be repeated at treatment midpoint and within one month of rTMS discontinuation in order to track structural and functional changes that occur over the course of treatment. Participants will complete an initial screening followed by 30-40 daily sessions of repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex (DLPFC), completed with their TMS provider. |
| Afternoon rTMS treatment | Experimental | Device: rTMS therapyEligible participants will be assigned to the afternoon treatment group. Prior to the onset of rTMS treatment, EEG scans and magnetic resonance imaging (MRI) sessions including diffusion weighted imaging will be recorded as baseline measures. These measures will also be repeated at treatment midpoint and within one month of rTMS discontinuation in order to track structural and functional changes that occur over the course of treatment. Participants will complete an initial screening followed by 30-40 daily sessions of repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex (DLPFC), completed with their TMS provider. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age 18-70
- Meet Diagnostic and Statistical Manual-V (DSM-V) diagnostic criteria for Major Depressive Disorder in a current major depressive episode, without psychotic features.
- Has Montgomery-Asberg Depressive Rating Scale (MADRS) of > 19 at baseline, corresponding with moderate to severe depression.
- Demonstrate a moderate level of resistance to antidepressant treatment in the current episode, defined as a failure of 1-4 adequate medication trials.
- If participant is on a regimen of psychotropic medication, no changes in this regimen should be made during the period between the time at which pre-treatment and post-treatment scans are taken.
Key exclusion criteria (12 listed)
- Diagnosed with acute or chronic psychotic symptoms of disorders (e.g. schizophrenia, schizophreniform, schizoaffective disorder) in the current depressive episode.
- Has neurological conditions including epilepsy, cerebrovascular disease, dementia, increased intracranial pressure, having a history of repetitive or severe head trauma, or with primary or secondary tumors in the central nervous system.
- Presence of an implanted magnetic-sensitive medical device in or near the head, including but not limited to pacemaker, vagus nerve stimulator, or metal aneurysm clips or coils, staples, or stents.
- Generalized anxiety disorder as the primary DSM-V disorder during the current MDD episode.
- Meets criteria for alcohol or substance abuse or dependence (other than caffeine) in previous 6 months, as determined by the SCID
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 |
|---|---|---|
| rTMS therapyAlso: repetitive TMS, repetitive transcranial magnetic stimulationrTMS treatment parameters will be determined by TMS care providers. Typical TMS settings for MDD involve rTMS applied at 10 Hz with an intensity of 120 % of resting motor threshold. Forty trains of 4 s duration with 11s of trains is typically applied (3000 pulses per day), resulting in approximately 90,000 pulses in a given treatment course. | Device | Afternoon rTMS treatment, Morning rTMS treatment |
Primary outcome
Change in MADRS score from baseline to end of treatment
Time frame: Up to one month prior to initial TMS session (baseline) to within one month following the completion of TMS treatment (~ 8 weeks)
Effect size of active stimulation (mean difference in Montgomery Asberg Depression Rating Scale (MADRS) score) before and after morning and afternoon treatment course. Higher MADRS score indicates more severe depression; the overall score ranges from 0 to 60.
Change in resting state BOLD signal from baseline to end of treatment
Time frame: Up to one month prior to initial TMS session (baseline) to within one month following the completion of TMS treatment (~ 8 weeks)
Change in resting state functional magnetic resonance imaging BOLD signal before and after the active treatment period.
Change in resting state EEG from baseline to end of treatment
Time frame: Up to one month prior to initial TMS session (baseline) to within one month following the completion of TMS treatment (~ 8 weeks)
Change in resting state EEG (electroencephalogram) alpha band coherence before and after the active treatment period.
Change in white matter integrity from baseline to end of treatment
Time frame: Up to one month prior to initial TMS session (baseline) to within one month following the completion of TMS treatment (~ 8 weeks)
Change in white matter integrity as measured by diffusion tensor imaging (DTI) before and after the active treatment period.
4 secondary outcomes
Change in Beck's Depression Inventory (BDI) score from baseline to end of treatment
Time frame: Up to one month prior to initial TMS session (baseline) to within one month following the completion of TMS treatment (~ 8 weeks)
Change in Patient Health Questionnaire (PHQ9) score from baseline to end of treatment
Time frame: Up to one month prior to initial TMS session (baseline) to within one month following the completion of TMS treatment (~ 8 weeks)
Change in Generalized Anxiety Disorder (GAD-7) score from baseline to end of treatment
Time frame: Up to one month prior to initial TMS session (baseline) to within one month following the completion of TMS treatment (~ 8 weeks)
Change in Inventory of Depressive Symptomatology (IDS-30 self report) score from baseline to end of treatment.
Time frame: Up to one month prior to initial TMS session (baseline) to within one month following the completion of TMS treatment (~ 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 30 Jan 2026.
- Individual participant dataSharing planned: No
Related trials for Depressive Disorder, Major
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.
Rebecca Martinez, MS contact
Andrew Krystal, MD, MS principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing rTMS therapy in people with Depressive Disorder, Major, run by University of California, San Francisco 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 9 inclusion and 12 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 30 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?
Contact Katherine Scangos, MD, PhD (415-476-7439, brainstim@ucsf.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in MADRS score from baseline to end of treatment (time frame: Up to one month prior to initial TMS session (baseline) to within one month following the completion of TMS treatment (~ 8 weeks)). The study lists 4 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 30 Jan 2026.