Depression, Treatment ResistantNCT06511544
rTMS to Target Neural Connectivity and Rumination in Treatment-Resistant Depression
A study testing Transcranial magnetic stimulation in people with Depression, Treatment Resistant, run by Indiana University at 1 site in United States.
Trial summary
The goal of this clinical trial is to learn if Transcranial Magnetic Stimulation (TMS) to part of the brain called the ventromedial prefrontal cortex (VMPFC) can treat a symptom called rumination in adults with major depression that has not responded to at least one medication trial. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Depression, Treatment Resistant
- What is being tested?
- Transcranial magnetic stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Jan 2024to 30 Jan 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
- Diagnosis of unipolar major depressive disorder without psychotic features by the Mini-International Neuropsychiatric Interview (MINI) and confirmed by study psychiatrist
- First depressive episode prior to age 50
- Current moderate to severe depression, Hamilton Depression Rating Scale (HDRS) ≥17)
- Failure to respond to ≥1 antidepressant medication at adequate dose and duration in the current depressive episode; (note: this criterion is designed to be consistent with the original 2008 FDA-labeled indication for TMS in Major Depressive Disorder, that specifies failure to respond to "one prior medication at or above the minimal effective dose and duration in the current episode" (https://www.accessdata.fda.gov/cdrh_docs/pdf8/K083538.pdf). ))
- Off psychotropic medications OR on a stable dose of medication(s) for 6 weeks, and willing to remain on stable medication dosage throughout the study
- Capacity to consent
- Ability to safely receive MRI
Who cannot join
- Actively/imminently suicidal, Quick Inventory of Depressive Symptomatology (QIDS) item 12 score >2)
- Current depressive episode duration > 5 years
- Presence of clinically significant psychiatric diagnoses other than unipolar, non-psychotic major depression, such as post-traumatic stress disorder (PTSD) or obsessive-compulsive disorder (OCD)
- Evidence of cognitive impairment, Montreal Cognitive Assessment (MOCA) < 23)
- Significant substance use disorder within past 6 months
- New-onset psychotherapy and/or somatic therapy (e.g., light therapy) within 6 weeks of screening
Show all 17Show fewer
- Prior exposure to any form of TMS
- Have participated in any clinical trial with an investigational drug or device within the past 6 weeks prior to screening
- Failure to respond to Electroconvulsive therapy (ECT)
- Any history of neurosurgery to treat a neurologic or psychiatric disorder (e.g. Vagus nerve stimulation, cortical stimulation, deep brain stimulation, or ablative surgery)
- Unstable medical illness
- Evidence or history of significant neurological disorder, including moderate-severe head trauma, stroke, Parkinson's disease or other movement disorder (except benign essential tremor)
- Epilepsy
- History of seizures (except juvenile febrile seizures or provoked seizures at the PI's discretion) or any condition/concurrent medication that could notably lower seizure threshold
- Pregnancy or planned pregnancy during the study
- Presence of cardiac pacemaker, cochlear implant, or other implanted electronic device
- Any vision problem that will prevent them from seeing the adjectives presented inside the MRI scanner without glasses
Trial locations and contacts
1 site in 1 country.
United States1 site
Goodman Hall Neuroscience Center
Indianapolis, Indiana, 46202
About this study
Official title: Repetitive Transcranial Magnetic Stimulation of the Ventromedial Prefrontal Cortex to Target Neural Connectivity and Rumination in Treatment-Resistant Major Depressive Disorder: A Pilot Study
The goal of this clinical trial is to learn if Transcranial Magnetic Stimulation (TMS) to part of the brain called the ventromedial prefrontal cortex (VMPFC) can treat a symptom called rumination in adults with major depression that has not responded to at least one medication trial. The main question it aims to answer are:
Does TMS to the VMPFC change brain activity on functional magnetic resonance imaging (fMRI) during a negative self-referential processing task in adults with depression? Does TMS to the VMPFC affect rumination in adults with depression? Researchers will compare brain scans and rumination scores before, during, and immediately after TMS.
Read more
Participants will:
Undergo three functional MRI scans Undergo a course of 20 TMS treatments Respond to clinical questionnaires and complete a computer behavioral task
Read the detailed description
This will be a single-site, pilot, open-label, within-subject design study. 20 participants with treatment-resistant depression, defined as a failure to respond to at least one antidepressant medication trial within a current major depressive episode, will be recruited. Prior to intervention, participants will undergo self-report and clinician-administered assessments (in-person or virtual with both audio and video on using secure health telecommunication method), as well as a fMRI during resting state and a self-referential processing task. The baseline scan will also include a high-resolution structural sequence for neuronavigational purposes. Then, participants will receive 20 daily (5 days/week) sessions of rTMS to the VMPFC along with weekly assessments. Participants will undergo a repeated fMRI scan early in the course of treatment (after session 5) when we would expect neural changes to be evident but prior to any robust overall antidepressant effect, as well as at the end of the rTMS course (after session 20). Scores on the depression and rumination scales will be recorded prior to intervention and weekly thereafter. Contact with subjects will be conducted once via telephone at two weeks after the end of study intervention as an adverse event assessment. In the event that new or persistent adverse events felt to be related to the study intervention occur following the termination of study procedures, subjects may be brought in for further safety assessments.
- Conditions
- Depression, Treatment Resistant
- Being tested
- Transcranial magnetic stimulation
- Keywords
- transcranial magnetic stimulation, functional magnetic resonance imaging
- 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.
Transcranial magnetic stimulationDevice
rTMS delivered at 1 Hz for 1800 pulses over 30 minutes for 20 daily sessions, 5 days/week. Treatment will be directed to the ventromedial prefrontal cortex using each participant's structural MRI.
| Study group | Role | What they receive |
|---|---|---|
| Active TMS | Experimental | All participants will receive active TMS to the VMPFC for 20 sessions Receives: Device: Transcranial magnetic stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Functional Connectivity
Within-network functional connectivity of the default mode network during negative processing
Measured: Before Transcranial magnetic stimulation (TMS) - immediately following TMS
Rumination
Scores on the Ruminative Response Scale (Range 22-88, with higher worse)
Measured: Before TMS- immediately following TMS
Secondary outcomes (1)
Overall Depression Scores
Hamilton Depression Rating Scale (Range 0-52, with higher worse)
Measured: Before TMS- immediately following TMS
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2024
- Study start2 Jan 2024
- Primary completion30 Jan 2027 (estimated)
- Study completion30 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Depression, Treatment ResistantStudies of the same condition, open and under way.
- More trials run by Indiana 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Collaborators
- National Center for Advancing Translational Sciences (NCATS)
- Responsible party
- Principal investigator, Susan K. Conroy, Indiana University
- Investigators
- Susan K Conroy, MD PhD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06511544
- Sponsor's protocol ID
- 13322
- Other IDs
- K12TR004415
- Status last verified
- Oct 2026
- First submitted
- 8 Jul 2024
- Last updated
- 4 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- 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 4 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Repetitive Transcranial Magnetic Stimulation of the Ventromedial Prefrontal Cortex to Target Neural Connectivity and Rumination in Treatment-Resistant Major Depressive Disorder: A Pilot Study
- ClinicalTrials.gov ID
- NCT06511544
- Acronym / sponsor ID
- 13322
- Conditions
- Depression, Treatment Resistant
- Keywords
- transcranial magnetic stimulation, functional magnetic resonance imaging
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- National Center for Advancing Translational Sciences (NCATS)
- Study start
- 2 Jan 2024 (actual)
- Primary completion
- 30 Jan 2027 (estimated)
- Study completion
- 30 Jan 2027 (estimated)
- First posted
- 22 Jul 2024 (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.
The goal of this clinical trial is to learn if Transcranial Magnetic Stimulation (TMS) to part of the brain called the ventromedial prefrontal cortex (VMPFC) can treat a symptom called rumination in adults with major depression that has not responded to at least one medication trial. The main question it aims to answer are:
Does TMS to the VMPFC change brain activity on functional magnetic resonance imaging (fMRI) during a negative self-referential processing task in adults with depression? Does TMS to the VMPFC affect rumination in adults with depression? Researchers will compare brain scans and rumination scores before, during, and immediately after TMS.
Participants will:
Undergo three functional MRI scans Undergo a course of 20 TMS treatments Respond to clinical questionnaires and complete a computer behavioral task
Detailed description
This will be a single-site, pilot, open-label, within-subject design study. 20 participants with treatment-resistant depression, defined as a failure to respond to at least one antidepressant medication trial within a current major depressive episode, will be recruited. Prior to intervention, participants will undergo self-report and clinician-administered assessments (in-person or virtual with both audio and video on using secure health telecommunication method), as well as a fMRI during resting state and a self-referential processing task. The baseline scan will also include a high-resolution structural sequence for neuronavigational purposes. Then, participants will receive 20 daily (5 days/week) sessions of rTMS to the VMPFC along with weekly assessments. Participants will undergo a repeated fMRI scan early in the course of treatment (after session 5) when we would expect neural changes to be evident but prior to any robust overall antidepressant effect, as well as at the end of the rTMS course (after session 20). Scores on the depression and rumination scales will be recorded prior to intervention and weekly thereafter. Contact with subjects will be conducted once via telephone at two weeks after the end of study intervention as an adverse event assessment. In the event that new or persistent adverse events felt to be related to the study intervention occur following the termination of study procedures, subjects may be brought in for further safety assessments.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Active TMS | Experimental | Device: Transcranial magnetic stimulationAll participants will receive active TMS to the VMPFC for 20 sessions |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Diagnosis of unipolar major depressive disorder without psychotic features by the Mini-International Neuropsychiatric Interview (MINI) and confirmed by study psychiatrist
- First depressive episode prior to age 50
- Current moderate to severe depression, Hamilton Depression Rating Scale (HDRS) ≥17)
- Failure to respond to ≥1 antidepressant medication at adequate dose and duration in the current depressive episode; (note: this criterion is designed to be consistent with the original 2008 FDA-labeled indication for TMS in Major Depressive Disorder, that specifies failure to respond to "one prior medication at or above the minimal effective dose and duration in the current episode" (https://www.accessdata.fda.gov/cdrh_docs/pdf8/K083538.pdf). ))
- Off psychotropic medications OR on a stable dose of medication(s) for 6 weeks, and willing to remain on stable medication dosage throughout the study
Key exclusion criteria (17 listed)
- Actively/imminently suicidal, Quick Inventory of Depressive Symptomatology (QIDS) item 12 score >2)
- Current depressive episode duration > 5 years
- Presence of clinically significant psychiatric diagnoses other than unipolar, non-psychotic major depression, such as post-traumatic stress disorder (PTSD) or obsessive-compulsive disorder (OCD)
- Evidence of cognitive impairment, Montreal Cognitive Assessment (MOCA) < 23)
- Significant substance use disorder within past 6 months
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 stimulationrTMS delivered at 1 Hz for 1800 pulses over 30 minutes for 20 daily sessions, 5 days/week. Treatment will be directed to the ventromedial prefrontal cortex using each participant's structural MRI. | Device | Active TMS |
Primary outcome
Functional Connectivity
Time frame: Before Transcranial magnetic stimulation (TMS) - immediately following TMS
Within-network functional connectivity of the default mode network during negative processing
Rumination
Time frame: Before TMS- immediately following TMS
Scores on the Ruminative Response Scale (Range 22-88, with higher worse)
1 secondary outcome
Overall Depression Scores
Time frame: Before TMS- immediately following TMS
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 4 Nov 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.
Susan K Conroy, MD PhD principal investigator
Indiana University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial magnetic stimulation in people with Depression, Treatment Resistant, run by Indiana 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 17 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 4 Nov 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?
Functional Connectivity (time frame: Before Transcranial magnetic stimulation (TMS) - immediately following TMS). 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 4 Nov 2026.