DepressionNCT06266390
Individualized (fMRI-guided) TMS Treatment for Depression
A study testing Transcranial Magnetic Stimulation (TMS) in people with Depression and Major Depressive Disorder, run by University of Pennsylvania at 1 site in United States.
Trial summary
The purpose of this study is to investigate the responses of the brain region known as the subgenual anterior cingulate cortex (sgACC) during transcranial magnetic stimulation (TMS) in individuals with depression. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Depression, Major Depressive Disorder, Persistent Depressive Disorder
- What is being tested?
- Transcranial Magnetic Stimulation (TMS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteUnited States
- Study dates
- 29 May 2024to 30 Jun 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- 18-65 years old
- DSM-5 diagnosis of major depressive (at least 90%) or persistent depressive disorder (no more than 10%) as per SCID clinical interview.
- Patient Health Questionnaire-9 (PHQ-9) score = or > than 10
- Comprehension of instructions in the English language.
- Capacity to provide informed consent and follow study procedures.
- Availability for the duration of the study.
Who cannot join
- Implanted medical devices, metallic implants, or drug infusion pumps that are not MRI-safe (e.g., aneurysm clips, defibrillators, or cochlear implants)
- History of significant medical events (e.g., stroke, seizures, brain scarring) or neurological/neurodevelopmental conditions (e.g., epilepsy) that are contraindications for TMS and MRI or may adversely affect brain function and data interpretation.
- Current psychosis, mania, or substance use disorder
- Prior failed response to full rTMS or ECT/MST trial. Any successful prior treatments are acceptable and support a prognosis that a new rTMS treatment would be worth attempting.
- Inability to complete an MRI scan (e.g., claustrophobia, inability to remain still for extended periods).
- Inability to tolerate TMS administration
Show all 23Show fewer
- Significant handicaps that would interfere with testing procedures
- Acute systemic infection, high fever
- Acute sleep deprivation or medication/substance intoxication or withdrawal (TMS seizure risk)
- Current use of cyclosporine, tacrolimus, or others that can cause leukoencephalopathy.
- Pregnancy
- Dialysis
- Suicide attempt in past 6 months (safety precaution)
- Current use of Bupropion (Wellbutrin) above 300 mg, benzodiazepines, lithium, monoamine oxidase inhibitors (MAOIs), and/or high doses of stimulant medication is exclusionary. Note: Exclusionary dosages or medications may be reduced or discontinued under the supervision of a medical provider. Participants must provide documentation confirming that their medical provider has agreed to oversee any medication changes, as abrupt changes can lower the seizure threshold and are contraindicated for TMS.
- Transportation limits or physical limits to attending daily M-F treatment sessions.
- Per study physician discretion medications likely to interfere with blood flow or otherwise compromise functional imaging measures.
- Any other factor that in the investigators' judgment may affect patient safety or compliance (e.g. distance greater than 100 miles from procedure site; unlikely to be able to schedule daily treatment sessions, etc.)
- In addition, during this study participants will be asked to:
- Refrain from substance use (including marijuana and illicit drugs) for the duration of the study
- Abstain from alcohol for 24 hours before study visits.
- Maintain a consistent level of caffeine consumption throughout the study period and avoid any significant increases.
- Not initiate, discontinue, or adjust any psychiatric medications or therapy treatments during the study period.
- Inform the study team of any new medical treatments or prescribed medications (e.g., antibiotics) to allow for safety review and determination of continued eligibility for the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Engaging the Subgenual Cingulate With Brain Stimulation for Depression
The purpose of this study is to investigate the responses of the brain region known as the subgenual anterior cingulate cortex (sgACC) during transcranial magnetic stimulation (TMS) in individuals with depression. Specifically, investigators aim to determine whether the sgACC is engaged when TMS is delivered to specific targets and if the engagement of sgACC changes throughout a full TMS treatment intervention. To achieve this goal, the investigators will employ a combination of TMS and Magnetic Resonance Imaging (MRI) procedures.
Study participation will include completing various questionnaires, clinical assessments, receiving a full transcranial magnetic stimulation (TMS) treatment intervention (every weekday for 6 weeks), and undergoing MRI scans, both with and without concurrent TMS.
Read the detailed description
Interested subjects will be asked to complete multiple questionnaires, a clinical interview, and a TMS demonstration to determine eligibility following the informed consent process.
If determined eligible, participants will proceed to undergo an MRI scan to generate their individualized TMS targets.The subsequent visit will involve the first MRI scanning session with concurrent TMS (TMS/fMRI), referred to as Baseline TMS/fMRI, along with the completion of multiple questionnaires.
Following the Baseline TMS/fMRI session, participants will begin the TMS treatment phase. This phase comprises daily sessions (Monday to Friday) for 6 weeks, during which participants will receive rTMS treatments and complete various surveys.
Midway through and upon completion of the TMS treatment intervention, two additional TMS/fMRI sessions will replicate the procedures conducted during the initial Baseline TMS/fMRI.
Remote follow-up assessments at 1, 6, and 12 months post-treatment will evaluate any enduring improvements in clinical symptoms.
Participants will be compensated for completing study procedures.
- Being tested
- Transcranial Magnetic Stimulation (TMS)
- Keywords
- Transcranial Magnetic Stimulation, Brain Imaging, Brain Stimulation, Depression, TMS, fMRI, non-invasive brain stimulation, TMS treatment, TMS for depression, individualized treatment
- Medical subject headings
- Depression, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Magnetic Stimulation (TMS)Device
The TMS intervention will involve two sets of Intermittent Theta-Burst Stimulation (iTBS) delivered every weekday for 4-6 weeks. Each iTBS set consists of 40 trains and a total of 1200 pulses, delivered approximately 15 minutes apart, resulting in 2400 pulses per session.
| Study group | Role | What they receive |
|---|---|---|
| Positive Correlation Target | Active comparator | TMS treatment will be administered using a TMS target positively correlated with the sgACC. Receives: Device: Transcranial Magnetic Stimulation (TMS) |
| Anticorrelation Target | Active comparator | TMS treatment will be administered using a TMS target anticorrelated with the sgACC. Receives: Device: Transcranial Magnetic Stimulation (TMS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
sgACC Blood Oxygen Level Dependent (BOLD) signal change following single-pulse fMRI-guided TMS (TMS On vs TMS Off)
This primary endpoint aims to directly assess sgACC engagement during fMRI-guided TMS by comparing sgACC BOLD signal under TMS On and TMS Off conditions. This sgACC BOLD signal change will be defined as sgACC evoked response henceforth.
Measured: Single visit (~2 hours)
Secondary outcomes (1)
Change in sgACC evoked response Pre/Post TMS treatment with positive and negative sgACC correlated targets
Test the efficacy of positive and negative functionally connected (FC) targets in inducing changes in sgACC evoked response (modulation) before and after TMS treatment.
Measured: Up to 7 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2024
- Study start29 May 2024
- Primary completion14 Apr 2026
- Study completion30 Jun 2026
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 University of PennsylvaniaThe 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
- Parallel groups
- Model description
- Participants will receive rTMS to one of two targets. Participants will be randomly assigned to receive the TMS treatment intervention in one of two target conditions: half to their positive sgACC correlation target, while the remaining half to their negative sgACC correlation target.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Desmond Oathes, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06266390
- Sponsor's protocol ID
- 855007
- Other IDs
- 1R61MH135428
- Status last verified
- Jul 2026
- First submitted
- 8 Jan 2024
- Last updated
- 23 Jul 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 23 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Engaging the Subgenual Cingulate With Brain Stimulation for Depression
- ClinicalTrials.gov ID
- NCT06266390
- Acronym / sponsor ID
- 855007
- Keywords
- Transcranial Magnetic Stimulation, Brain Imaging, Brain Stimulation, Depression, TMS, fMRI, non-invasive brain stimulation, TMS treatment
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Mental Health (NIMH)
- Study start
- 29 May 2024 (actual)
- Primary completion
- 14 Apr 2026 (actual)
- Study completion
- 30 Jun 2026 (actual)
- First posted
- 20 Feb 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 purpose of this study is to investigate the responses of the brain region known as the subgenual anterior cingulate cortex (sgACC) during transcranial magnetic stimulation (TMS) in individuals with depression. Specifically, investigators aim to determine whether the sgACC is engaged when TMS is delivered to specific targets and if the engagement of sgACC changes throughout a full TMS treatment intervention. To achieve this goal, the investigators will employ a combination of TMS and Magnetic Resonance Imaging (MRI) procedures.
Study participation will include completing various questionnaires, clinical assessments, receiving a full transcranial magnetic stimulation (TMS) treatment intervention (every weekday for 6 weeks), and undergoing MRI scans, both with and without concurrent TMS.
Detailed description
Interested subjects will be asked to complete multiple questionnaires, a clinical interview, and a TMS demonstration to determine eligibility following the informed consent process.
If determined eligible, participants will proceed to undergo an MRI scan to generate their individualized TMS targets.The subsequent visit will involve the first MRI scanning session with concurrent TMS (TMS/fMRI), referred to as Baseline TMS/fMRI, along with the completion of multiple questionnaires.
Following the Baseline TMS/fMRI session, participants will begin the TMS treatment phase. This phase comprises daily sessions (Monday to Friday) for 6 weeks, during which participants will receive rTMS treatments and complete various surveys.
Midway through and upon completion of the TMS treatment intervention, two additional TMS/fMRI sessions will replicate the procedures conducted during the initial Baseline TMS/fMRI.
Remote follow-up assessments at 1, 6, and 12 months post-treatment will evaluate any enduring improvements in clinical symptoms.
Participants will be compensated for completing study procedures.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Participants will receive rTMS to one of two targets. Participants will be randomly assigned to receive the TMS treatment intervention in one of two target conditions: half to their positive sgACC correlation target, while the remaining half to their negative sgACC correlation target.
| Arm | Type | Receives |
|---|---|---|
| Positive Correlation Target | Active comparator | Device: Transcranial Magnetic Stimulation (TMS)TMS treatment will be administered using a TMS target positively correlated with the sgACC. |
| Anticorrelation Target | Active comparator | Device: Transcranial Magnetic Stimulation (TMS)TMS treatment will be administered using a TMS target anticorrelated with the sgACC. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 18-65 years old
- DSM-5 diagnosis of major depressive (at least 90%) or persistent depressive disorder (no more than 10%) as per SCID clinical interview.
- Patient Health Questionnaire-9 (PHQ-9) score = or > than 10
- Comprehension of instructions in the English language.
- Capacity to provide informed consent and follow study procedures.
Key exclusion criteria (23 listed)
- Implanted medical devices, metallic implants, or drug infusion pumps that are not MRI-safe (e.g., aneurysm clips, defibrillators, or cochlear implants)
- History of significant medical events (e.g., stroke, seizures, brain scarring) or neurological/neurodevelopmental conditions (e.g., epilepsy) that are contraindications for TMS and MRI or may adversely affect brain function and data interpretation.
- Current psychosis, mania, or substance use disorder
- Prior failed response to full rTMS or ECT/MST trial. Any successful prior treatments are acceptable and support a prognosis that a new rTMS treatment would be worth attempting.
- Inability to complete an MRI scan (e.g., claustrophobia, inability to remain still for extended periods).
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 Stimulation (TMS)The TMS intervention will involve two sets of Intermittent Theta-Burst Stimulation (iTBS) delivered every weekday for 4-6 weeks. Each iTBS set consists of 40 trains and a total of 1200 pulses, delivered approximately 15 minutes apart, resulting in 2400 pulses per session. | Device | Anticorrelation Target, Positive Correlation Target |
Primary outcome
sgACC Blood Oxygen Level Dependent (BOLD) signal change following single-pulse fMRI-guided TMS (TMS On vs TMS Off)
Time frame: Single visit (~2 hours)
This primary endpoint aims to directly assess sgACC engagement during fMRI-guided TMS by comparing sgACC BOLD signal under TMS On and TMS Off conditions. This sgACC BOLD signal change will be defined as sgACC evoked response henceforth.
1 secondary outcome
Change in sgACC evoked response Pre/Post TMS treatment with positive and negative sgACC correlated targets
Time frame: Up to 7 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2026.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 (TMS) in people with Depression and Major Depressive Disorder, run by University of Pennsylvania 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 6 inclusion and 23 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: finished, as of the sponsor's last update on 23 Jul 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
sgACC Blood Oxygen Level Dependent (BOLD) signal change following single-pulse fMRI-guided TMS (TMS On vs TMS Off) (time frame: Single visit (~2 hours)). 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 Jul 2026.