Depression - Major Depressive DisorderPhase 4BioSelectNCT07680140
Biomarker-Guided Antidepressant Selection
A Phase 4 study testing TMS and Ketamine in people with Depression - Major Depressive Disorder and Treatment-resistant Depression (TRD), run by Weill Medical College of Cornell University at 1 site in United States.
Trial summary
Depression is one of the leading causes of disability worldwide. Common treatments like antidepressant medications and talk therapy work well for some people, but many others do not improve, even after trying multiple treatments. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD), rTMS
- What is being tested?
- TMS and Ketamine
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Aug 2026to Dec 2028
- Phase
- Phase 4
- 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
- Provision of signed and dated informed consent form
- Adults of all genders aged 18-70 at the time of screening
- Diagnosis of Major Depressive Disorder (by DSM-5 criteria)
- Depressive symptoms of at least moderate severity (GRID HDRS-17 score >= 14 or as determined by a study clinician)
- Failed at least 1 prior trial of standard first-line treatment for MDD per the modified Antidepressant Treatment History form, the Maudsley Staging Method, and APA Practice Guidelines (e.g., SSRI, SNRI, CBT) OR initiated and discontinued a trial of a first-line treatment for MDD (e.g. could not tolerate side effects, etc.)
- Not currently taking antidepressants OR on a stable dose of antidepressant for at least 1month prior to screening and plans to remain off antidepressants OR on this stable dose for the duration of participation
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- Current medication regimen is compatible with safe participation in the trial in the assessment of a study clinician
- Access to psychiatric care before, during, and after completion of the study
- For females of reproductive potential: agreement to use effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation
- Proficiency in English sufficient to complete assessments and follow study procedure instructions
- Stated willingness to comply with all study procedures and availability for the duration of the study
Who cannot join
- Imminent risk of suicide
- Presence of primary psychiatric diagnosis other than MDD (e.g., post-traumatic stress disorder, obsessive-compulsive disorder, MDD with psychotic features, primary psychotic illness, bipolar I or II disorder)
- History of epilepsy or a history of seizures that would influence the participant's risk for TMS-evoked seizures; history of any condition / concurrent medication that could notably lower seizure threshold in the estimation of a study clinician
- Met criteria for any clinically significant substance use disorder (by DSM-V criteria) with active substance misuse in the 6 months prior to screening
- Lifetime history of PCP/ketamine abuse
- History or presence of significant neurological disorder that may be contributing to current depressive symptoms in the judgment of a study clinician (e.g., traumatic brain injury, stroke, Parkinson's disease or other movement disorder, epilepsy)
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- Presence of medical contraindications to ketamine, including liver function tests > 2.5x normal limit, recent myocardial infarction, congestive heart failure > stage 2, angina pectoris, clinically significant bradycardia or tachycardia at the baseline assessment, or uncontrolled hypertension
- MRI contraindication, including presence of ferromagnetic foreign metal bodies or implants, implanted or conductive ferromagnetic objects in or near the head (e.g., stents, deep brain stimulators, vagus nerve stimulators, aneurysm coils, ocular implants, cochlear implants), and ferromagnetic permanent make-up that may undergo heating in an MRI scanner
- Individuals who are nursing, pregnant, or contemplating pregnancy within the length of study participation
- Abnormal bloodwork that may be contributing to depressive symptoms in the estimation of a study clinician (e.g. indicators of clinically significant hypothyroidism, kidney failure, liver failure, etc.)
- History or presence of any disorder or medical condition that, in the opinion of the study team, may compromise, interfere, or limit the individual's ability to complete the intervention or study procedures
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
Weill Cornell Medicine
New York, New York, 10065
Research Coordinator, Interventional Psychiatry Program, 646-962-2900, tmsinfo@med.cornell.edu
Conor Liston, MD, PhD
About this study
Official title: Biomarker-Guided Antidepressant Selection for Treatment-Resistant Depression
Depression is one of the leading causes of disability worldwide. Common treatments like antidepressant medications and talk therapy work well for some people, but many others do not improve, even after trying multiple treatments.
This study will investigate two alternative treatment options for people whose depression has not responded to standard treatments: repetitive transcranial magnetic stimulation (rTMS), a non-invasive form of brain stimulation, and ketamine, a fast-acting medication. It can be difficult to decide between these interventions in clinical practice, and selecting between them often comes down to patient preference and trial and error. This study is working to optimize the selection approach: using biological and behavioral markers to match each person to identify biomarkers that may predict response to rTMS or ketamine. Investigators believe that differences in how individuals respond to rTMS versus ketamine are partly explained by differences in how their brains are organized, and that these differences can be measured and used to guide intervention decisions. This is an early-stage pilot study designed to test whether this biomarker-based approach is practical and acceptable to patients. Investigators will evaluate how well a combination of brain imaging and clinical data can predict, at the individual level, who is likely to respond to rTMS versus ketamine. The ultimate goal is to develop a reliable, scalable tool that helps clinicians make faster and more informed intervention decisions, reducing the time people with treatment-resistant depression spend searching for an antidepressant that works.
- Conditions
- Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD), rTMS, Ketamine, fMRI
- Being tested
- TMS, Ketamine
- Medical subject headings
- Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TMSDevice
rTMS will be administered as intermittent theta burst simulation (iTBS) delivered to the left dorsolateral prefrontal cortex with an accelerated intervention protocol (up to 5 consecutive days of 10 hourly rTMS sessions).
KetamineDrug
Ketamine is a dissociative anesthetic with rapid-acting antidepressant properties. It will be administered in 6 total sessions (3 days x 2 weeks), each comprising a single subanesthetic dose of ketamine (0.5 mg/kg) delivered intravenously over 40 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Repetitive Transcranial Magnetic Stimulation (rTMS) | Experimental | Not described Receives: Device: TMS |
| Ketamine | Experimental | Not described Receives: Drug: Ketamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from Baseline to 2-Week Post-Intervention Score in Hamilton Depression Rating Scale (HDRS) Score
Change in depressive symptoms from pre- to post-intervention, as measured by mean percent change in score on the GRID 17-item Hamilton Depression Rating Scale (HDRS-17), in participants receiving rTMS vs. ketamine. The GRID HDRS-17 has a minimum score of 0 and maximum score of 52, with higher scores indicating greater depression severity.
Measured: Baseline to 2-weeks post-intervention
Secondary outcomes (1)
Change from Baseline to Post-Intervention on a Visual Analog Scale of the Antidepressant Selection Approach
Ratings on a visual analog scale assessing whether the study visits (including MRI scans and clinical assessments) are tolerable and perceived to be an acceptable component of future intervention protocols. The scale will be scored from -10 to +10, with higher scores indicating higher acceptability. Secondary outcome analyses will use a one-sample t-test to evaluate whether visual analog scores are significantly greater than zero.
Measured: From screening to the end of follow-up at 8-weeks post-intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2026
- Study start10 Aug 2026
- Primary completionSep 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Depression - Major Depressive DisorderStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 27 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Collaborators
- Icahn School of Medicine at Mount Sinai, National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Conor Liston, MD, PhD, Principal investigator, Weill Medical College of Cornell University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07680140
- Sponsor's protocol ID
- 26-02029842
- Other IDs
- UG3MH137656
- Acronym
- BioSelect
- Status last verified
- Sep 2026
- First submitted
- 25 Jun 2026
- Last updated
- 23 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in the primary outcomes publication, after de-identification, will be shared. Supporting documents including the study protocol and informed consent form will be available. Analytic pipelines used in published analyses will be made publicly available via GitHub.
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biomarker-Guided Antidepressant Selection for Treatment-Resistant Depression
- ClinicalTrials.gov ID
- NCT07680140
- Acronym / sponsor ID
- BioSelect / 26-02029842
- Conditions
- Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD), rTMS, Ketamine, fMRI
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 27 participants (estimated)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Collaborators
- Icahn School of Medicine at Mount Sinai, National Institute of Mental Health (NIMH)
- Study start
- 10 Aug 2026 (actual)
- Primary completion
- Sep 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 2 Jul 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.
Depression is one of the leading causes of disability worldwide. Common treatments like antidepressant medications and talk therapy work well for some people, but many others do not improve, even after trying multiple treatments.
This study will investigate two alternative treatment options for people whose depression has not responded to standard treatments: repetitive transcranial magnetic stimulation (rTMS), a non-invasive form of brain stimulation, and ketamine, a fast-acting medication. It can be difficult to decide between these interventions in clinical practice, and selecting between them often comes down to patient preference and trial and error. This study is working to optimize the selection approach: using biological and behavioral markers to match each person to identify biomarkers that may predict response to rTMS or ketamine. Investigators believe that differences in how individuals respond to rTMS versus ketamine are partly explained by differences in how their brains are organized, and that these differences can be measured and used to guide intervention decisions. This is an early-stage pilot study designed to test whether this biomarker-based approach is practical and acceptable to patients. Investigators will evaluate how well a combination of brain imaging and clinical data can predict, at the individual level, who is likely to respond to rTMS versus ketamine. The ultimate goal is to develop a reliable, scalable tool that helps clinicians make faster and more informed intervention decisions, reducing the time people with treatment-resistant depression spend searching for an antidepressant that works.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Repetitive Transcranial Magnetic Stimulation (rTMS) | Experimental | Device: TMS |
| Ketamine | Experimental | Drug: Ketamine |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Provision of signed and dated informed consent form
- Adults of all genders aged 18-70 at the time of screening
- Diagnosis of Major Depressive Disorder (by DSM-5 criteria)
- Depressive symptoms of at least moderate severity (GRID HDRS-17 score >= 14 or as determined by a study clinician)
- Failed at least 1 prior trial of standard first-line treatment for MDD per the modified Antidepressant Treatment History form, the Maudsley Staging Method, and APA Practice Guidelines (e.g., SSRI, SNRI, CBT) OR initiated and discontinued a trial of a first-line treatment for MDD (e.g. could not tolerate side effects, etc.)
Key exclusion criteria (11 listed)
- Imminent risk of suicide
- Presence of primary psychiatric diagnosis other than MDD (e.g., post-traumatic stress disorder, obsessive-compulsive disorder, MDD with psychotic features, primary psychotic illness, bipolar I or II disorder)
- History of epilepsy or a history of seizures that would influence the participant's risk for TMS-evoked seizures; history of any condition / concurrent medication that could notably lower seizure threshold in the estimation of a study clinician
- Met criteria for any clinically significant substance use disorder (by DSM-V criteria) with active substance misuse in the 6 months prior to screening
- Lifetime history of PCP/ketamine abuse
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 |
|---|---|---|
| TMSrTMS will be administered as intermittent theta burst simulation (iTBS) delivered to the left dorsolateral prefrontal cortex with an accelerated intervention protocol (up to 5 consecutive days of 10 hourly rTMS sessions). | Device | Repetitive Transcranial Magnetic Stimulation (rTMS) |
| KetamineKetamine is a dissociative anesthetic with rapid-acting antidepressant properties. It will be administered in 6 total sessions (3 days x 2 weeks), each comprising a single subanesthetic dose of ketamine (0.5 mg/kg) delivered intravenously over 40 minutes. | Drug | Ketamine |
Primary outcome
Change from Baseline to 2-Week Post-Intervention Score in Hamilton Depression Rating Scale (HDRS) Score
Time frame: Baseline to 2-weeks post-intervention
Change in depressive symptoms from pre- to post-intervention, as measured by mean percent change in score on the GRID 17-item Hamilton Depression Rating Scale (HDRS-17), in participants receiving rTMS vs. ketamine. The GRID HDRS-17 has a minimum score of 0 and maximum score of 52, with higher scores indicating greater depression severity.
1 secondary outcome
Change from Baseline to Post-Intervention on a Visual Analog Scale of the Antidepressant Selection Approach
Time frame: From screening to the end of follow-up at 8-weeks post-intervention
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 23 Sep 2026.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in the primary outcomes publication, after de-identification, will be shared. Supporting documents including the study protocol and informed consent form will be available. Analytic pipelines used in published analyses will be made publicly available via GitHub.
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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.
Conor Liston, MD, PhD principal investigator
Weill Medical College of Cornell University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing TMS and Ketamine in people with Depression - Major Depressive Disorder and Treatment-resistant Depression (TRD), run by Weill Medical College of Cornell 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 11 inclusion and 11 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 23 Sep 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 Research Coordinator, Interventional Psychiatry Program (646-962-2900, tmsinfo@med.cornell.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from Baseline to 2-Week Post-Intervention Score in Hamilton Depression Rating Scale (HDRS) Score (time frame: Baseline to 2-weeks post-intervention). 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 23 Sep 2026.