Major Depressive DisorderPhase 2ExpeditionNCT06376734
Search for Novel Transcranial Magnetic Stimulation (TMS) Targets for Mental Illness
A Phase 2 study testing Transcranial magnetic stimulation in people with Major Depressive Disorder and Obsessive-Compulsive Disorder, run by Brigham and Women's Hospital at 2 sites in United States.
Trial summary
Participants will receive Transcranial Magnetic Stimulation (TMS) at a random location in the left prefrontal cortex, excluding sites that are potentially unsafe. Extensive behavioral testing will be conducted to determine which behaviors are modulated by stimulating which circuits. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder, Obsessive-Compulsive Disorder, Schizophrenia
- 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
- 180 participants
- Where
- 2 sitesUnited States
- Study dates
- 30 Jan 2025to 1 Jun 2030
- Phase
- Phase 2
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-65
- English proficiency sufficient for informed consent, questionnaires/tasks, and treatment
- Primary diagnosis of one of the following: major depressive disorder (MDD), obsessive-compulsive disorder (OCD), generalized anxiety disorder (GAD), or schizophrenia (determined by focal assessment using the Structured Clinical Interview for DSM-5)
- ≥20 on the Beck Depression Inventory for patients with MDD
- ≥16 on the Beck Anxiety Inventory for patients with GAD
- ≥16 on the Yale-Brown Obsessive-Compulsive Scale for patients with OCD
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- ≥58 on the Positive and Negative Symptom Scale for patients with schizophrenia
- Stable psychotropic medication regimen, or remain medication free, for 4 weeks prior to treatment (Medication changes during study enrollment period will be tracked for post hoc analysis).
- Primary clinician (e.g. psychiatrist, therapist, psychologist, APRN, PA, etc.) responsible for psychiatric care before, during, and after the trial
Who cannot join
- Active pregnancy as determined by a urine pregnancy test
- Cluster B personality disorders (antisocial personality disorder, borderline personality disorder, histrionic personality disorder, narcissistic personality disorder)
- PTSD with active, clinically significant symptoms, as determined by clinician
- Diagnosis of Schizoaffective Disorder, Bipolar Type
- Recent (within 4 weeks) or concurrent use of rapid-acting antidepressant agent (ketamine/esketamine/ECT)
- Ferromagnetic metallic implant that would contraindicate receiving TMS or obtaining MRI
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- Any other TMS or MRI safety concerns identified by the clinician
- Receiving or planning to receive other TMS treatments during course of participation
- History of:
- Neurosurgical intervention for mental illness
- Moderate to severe autism spectrum disorder
- Intellectual disability
- Severe cognitive impairment
- Significant neurological illness (e.g., dementia, Parkinson's, Huntington's, brain tumor, seizure disorder, subdural hematoma, multiple sclerosis)
- Untreated or insufficiently treated endocrine disorder
- Eating disorders
- Treatment with investigational drug or intervention during the study period
- Current evidence of:
- Mania or hypomania
- Active suicidal ideation or a suicide attempt within the past year
- Contraindications to either TMS or MRI (e.g., metallic implants, etc.).
- Current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal
- Significantly increased seizure risk as determined by a clinician
- For participants with schizophrenia:
- Evidence of impaired capacity to consent, e.g. impaired insight into illness, as deemed by a licensed psychiatrist or psychologist on the study team
- Hospitalization with psychosis in the past 6 months
- Positive urine drug screen for illicit substances
- Existing tinnitus (ringing in the ears)
- Any other condition deemed by the PI to interfere with the study or increase risk to the participant
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 1 recruiting
- Active, not recruiting
Brigham and Women's Hospital
Boston, Massachusetts, 02115
- Recruiting
Acacia Clinics
Sunnyvale, California, 94087
Danielle DeSouza, PhD, 857-307-0294, expedition@mgb.org
Danielle DeSouza, MD
About this study
Official title: Transdiagnostic Circuit Mapping of Prefrontal Targets in Accelerated Transcranial Magnetic Stimulation
Participants will receive Transcranial Magnetic Stimulation (TMS) at a random location in the left prefrontal cortex, excluding sites that are potentially unsafe. Extensive behavioral testing will be conducted to determine which behaviors are modulated by stimulating which circuits.
Read the detailed description
Patients who meet inclusion criteria for a primary diagnosis of MDD, OCD, GAD, or Schizophrenia (n=90) and consent to treatment will be assigned two random stimulation sites in the left prefrontal cortex and receive 2 days of accelerated iTBS treatment at the first stimulation site. Patients will have a 2 month break before coming back for 2 days of accelerated iTBS treatment at the second stimulation site. Patients with schizophrenia will be offered to participate in a third arm of the trial using a schizophrenia-specific target. This arm will also include fMRI scans and behavioral testing pre- and post- aiTBS. There will be two days (6 hours total) of behavioral testing and MRI scanning before each stimulation session and two days (6 hours total) after each stimulation session. Participants will be given the option of completing the behavioral testing in one day, before and after stimulation sessions. All the patients will receive active stimulation, which will facilitate enrollment and eliminate ethical concerns about placebo treatment in vulnerable patient populations. All participants will be blinded to their target coordinates and scales will be administered by a blinded study staff.
- Conditions
- Major Depressive Disorder, Obsessive-Compulsive Disorder, Schizophrenia, Generalized Anxiety Disorder, Mood Disorders, Psychiatric Disorder
- Being tested
- Transcranial magnetic stimulation
- Keywords
- depression, anxiety, schizophrenia, OCD, obsessive-compulsive disorder, transcranial magnetic stimulation, TMS, accelerated TMS, accelerated intermittent theta burst stimulation, brain stimulation, neuromodulation, transdiagnostic, neuronavigation, functional connectivity, neuroimaging, theta burst stimulation
- Medical subject headings
- Depressive Disorder, Major, Obsessive-Compulsive Disorder, Schizophrenia, Generalized Anxiety Disorder, Mood Disorders, Mental Disorders, Depression, Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial magnetic stimulationDevice
Accelerated TMS will be provided for 2 days using the same dosing regimen as the FDA-cleared SAINT protocol, ten 9-minute treatments per day.
| Study group | Role | What they receive |
|---|---|---|
| TMS to random PFC location 1 | Experimental | Participants will receive 2 days of accelerated TMS (10 treatments per day) to a random location in the prefrontal cortex. Receives: Device: Transcranial magnetic stimulation |
| TMS to random PFC location 2 | Experimental | After a 2-month washout following arm 1, participants will receive another two days of accelerated iTBS treatment at a different random PFC location. Receives: Device: Transcranial magnetic stimulation |
| TMS to Schizophrenia location | Experimental | Patients with schizophrenia will be offered to participate in a third arm of the trial, during which participants will receive 2 days of accelerated iTBS to a schizophrenia-specific target. Receives: Device: Transcranial magnetic stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clustering of multiple behavioral measures
The primary outcome is that stimulation of different circuits will selectively modify different behavioral clusters. Participants will complete the following phenotyping battery tasks and questionnaires:
Q-SCID PANSS SAPS SANS PYRATS CDSS YBOCS CGI ATQ ASI BAI BDI BIS/BAS Claremont Purpose Scale De Jong Gierveld Loneliness Scale Daily Spiritual Experience Scale Emotional Reactivity Scale Flourishing Measures Headache Impact Test HiTOP-Self Report Moral Judgment Scale Pain Screener Personal Relationship with God Scale PSQI Positive and Negative Affect Scale Ruminative Response Scale Self Compassion-Short Form Spiritual Transcendence Scale- Short Form Temporal Experience of Pleasure Scale Values and Beliefs of the American Public Altruistic Decision Task Balloon Analogue Risk Task DSIAT EEfRT MSIT ECR Time perception task TMB toolkit 5min AV recording
Measured: through study completion, average of 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2024
- Study start30 Jan 2025
- Primary completion1 Jun 2029 (estimated)
- Study completion1 Jun 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe 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 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Double-blind, randomized controlled crossover trial. Participants will be stimulated at a random location in the prefrontal cortex, which will be mapped to its underlying brain network to determine which network was stimulated.
- Masking
- None (open label)
- Enrolment
- 180 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Shan Siddiqi, MD, Harvard Medical School (HMS and HSDM)
- Investigators
- Shan H Siddiqi, MD, Principal investigator, Brigham and Women's
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06376734
- Sponsor's protocol ID
- 2024p000528
- Acronym
- Expedition
- Status last verified
- Feb 2026
- First submitted
- 31 Mar 2024
- Last updated
- 16 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: De-identified survey response data and/or neuroimaging data may be shared with collaborators for further analysis.
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transdiagnostic Circuit Mapping of Prefrontal Targets in Accelerated Transcranial Magnetic Stimulation
- ClinicalTrials.gov ID
- NCT06376734
- Acronym / sponsor ID
- Expedition / 2024p000528
- Conditions
- Major Depressive Disorder, Obsessive-Compulsive Disorder, Schizophrenia, Generalized Anxiety Disorder, Mood Disorders, Psychiatric Disorder
- Keywords
- depression, anxiety, schizophrenia, OCD, obsessive-compulsive disorder, transcranial magnetic stimulation, TMS, accelerated TMS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 30 Jan 2025 (actual)
- Primary completion
- 1 Jun 2029 (estimated)
- Study completion
- 1 Jun 2030 (estimated)
- First posted
- 19 Apr 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.
Participants will receive Transcranial Magnetic Stimulation (TMS) at a random location in the left prefrontal cortex, excluding sites that are potentially unsafe. Extensive behavioral testing will be conducted to determine which behaviors are modulated by stimulating which circuits.
Detailed description
Patients who meet inclusion criteria for a primary diagnosis of MDD, OCD, GAD, or Schizophrenia (n=90) and consent to treatment will be assigned two random stimulation sites in the left prefrontal cortex and receive 2 days of accelerated iTBS treatment at the first stimulation site. Patients will have a 2 month break before coming back for 2 days of accelerated iTBS treatment at the second stimulation site. Patients with schizophrenia will be offered to participate in a third arm of the trial using a schizophrenia-specific target. This arm will also include fMRI scans and behavioral testing pre- and post- aiTBS. There will be two days (6 hours total) of behavioral testing and MRI scanning before each stimulation session and two days (6 hours total) after each stimulation session. Participants will be given the option of completing the behavioral testing in one day, before and after stimulation sessions. All the patients will receive active stimulation, which will facilitate enrollment and eliminate ethical concerns about placebo treatment in vulnerable patient populations. All participants will be blinded to their target coordinates and scales will be administered by a blinded study staff.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Double-blind, randomized controlled crossover trial. Participants will be stimulated at a random location in the prefrontal cortex, which will be mapped to its underlying brain network to determine which network was stimulated.
| Arm | Type | Receives |
|---|---|---|
| TMS to random PFC location 1 | Experimental | Device: Transcranial magnetic stimulationParticipants will receive 2 days of accelerated TMS (10 treatments per day) to a random location in the prefrontal cortex. |
| TMS to random PFC location 2 | Experimental | Device: Transcranial magnetic stimulationAfter a 2-month washout following arm 1, participants will receive another two days of accelerated iTBS treatment at a different random PFC location. |
| TMS to Schizophrenia location | Experimental | Device: Transcranial magnetic stimulationPatients with schizophrenia will be offered to participate in a third arm of the trial, during which participants will receive 2 days of accelerated iTBS to a schizophrenia-specific target. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age 18-65
- English proficiency sufficient for informed consent, questionnaires/tasks, and treatment
- Primary diagnosis of one of the following: major depressive disorder (MDD), obsessive-compulsive disorder (OCD), generalized anxiety disorder (GAD), or schizophrenia (determined by focal assessment using the Structured Clinical Interview for DSM-5)
- Stable psychotropic medication regimen, or remain medication free, for 4 weeks prior to treatment (Medication changes during study enrollment period will be tracked for post hoc analysis).
- Primary clinician (e.g. psychiatrist, therapist, psychologist, APRN, PA, etc.) responsible for psychiatric care before, during, and after the trial
Key exclusion criteria (29 listed)
- Active pregnancy as determined by a urine pregnancy test
- Cluster B personality disorders (antisocial personality disorder, borderline personality disorder, histrionic personality disorder, narcissistic personality disorder)
- PTSD with active, clinically significant symptoms, as determined by clinician
- Diagnosis of Schizoaffective Disorder, Bipolar Type
- Recent (within 4 weeks) or concurrent use of rapid-acting antidepressant agent (ketamine/esketamine/ECT)
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 stimulationAccelerated TMS will be provided for 2 days using the same dosing regimen as the FDA-cleared SAINT protocol, ten 9-minute treatments per day. | Device | TMS to Schizophrenia location, TMS to random PFC location 1, TMS to random PFC location 2 |
Primary outcome
Clustering of multiple behavioral measures
Time frame: through study completion, average of 3 months
The primary outcome is that stimulation of different circuits will selectively modify different behavioral clusters. Participants will complete the following phenotyping battery tasks and questionnaires: Q-SCID PANSS SAPS SANS PYRATS CDSS YBOCS CGI ATQ ASI BAI BDI BIS/BAS Claremont Purpose Scale De Jong Gierveld Loneliness Scale Daily Spiritual Experience Scale Emotional Reactivity Scale Flourishing Measures Headache Impact Test HiTOP-Self Report Moral Judgment Scale Pain Screener Personal Relationship with God Scale PSQI Positive and Negative Affect Scale Ruminative Response Scale Self Compassion-Short Form Spiritual Transcendence Scale- Short Form Temporal Experience of Pleasure Scale Values and Beliefs of the American Public Altruistic Decision Task Balloon Analogue Risk Task DSIAT EEfRT MSIT ECR Time perception task TMB toolkit 5min AV recording
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 16 Jul 2026.
- Individual participant dataSharing planned: Undecided. De-identified survey response data and/or neuroimaging data may be shared with collaborators for further analysis.
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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.
Shan H Siddiqi, MD principal investigator
Brigham and Women's
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Transcranial magnetic stimulation in people with Major Depressive Disorder and Obsessive-Compulsive Disorder, run by Brigham and Women's Hospital at 2 sites 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 29 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 16 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 2 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Emily Aquadro, MD (857-307-0294, expedition@mgb.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clustering of multiple behavioral measures (time frame: through study completion, average of 3 months). 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 16 Jul 2026.