Depressive Disorder, MajorPhase 2AINTNCT05680727
Individualized Functional Connectivity Targeting in aiTBS for Depression
A Phase 2 study testing transcranial magnetic stimulation in people with Depressive Disorder, Major and Depression, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
The goal of this clinical trial is to estimate the importance of neuroimaging in accelerated intermittent theta burst stimulation (aiTBS) for depression. Participants will receive aiTBS treatment, but they will not know if their treatment spot was found with neuroimaging or head measurements. Read more about this study
- Who is it for?
- Ages 22 to 80 years
- Conditions the study is for
- Depressive Disorder, Major, Depression, Mood Disorders
- What is being tested?
- transcranial magnetic stimulation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jul 2023to 17 Feb 2026
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 22 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- English proficiency sufficient for informed consent, questionnaires/tasks, and treatment
- Primary diagnosis of major depressive disorder per Diagnostic and Statistical Manual (DSM)-V criteria (MINI International Neuropsychiatric Interview)
- >20 on BDI
- >20 on the MADRS 10, 11
- Moderate to severe level of treatment resistance (Maudsley Staging Method)
- Stable antidepressant medication regimen, or remain medication free, for 4 weeks prior to treatment and to remain on this regimen throughout the study (including all follow-up assessments after the 5-day treatment protocol).
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- Primary clinician responsible for psychiatric care before, during, and after the trial
- Agreement to lifestyle considerations
- Abstain from becoming pregnant from screening through end of treatment
- Continue usual intake patterns of caffeine- or xanthine-containing products (e.g., coffee, tea, soft drinks, chocolate) throughout treatment
- Abstain from alcohol for at least 24 hours before the start of each MRI and TMS session
- Abstain from tobacco products during treatment day
Who cannot join
- Active pregnancy as determined by a urine pregnancy test
- Primary psychiatric diagnosis other than major depressive disorder requiring treatment other than comorbid anxiety disorder
- Those who did not respond to electroconvulsive therapy (ECT) after 8 sessions
- Recent (within 4 weeks) or concurrent use of rapid acting antidepressant agent (ketamine/esketamine/ECT)
- History of:
- Prior exposure to TMS
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- Neurosurgical intervention for depression
- 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, brain lesion)
- Untreated or insufficiently treated endocrine disorder
- Treatment with investigational drug or intervention during the study period
- Depth-adjusted TMS treatment dose > 65% maximum stimulator output
- ≥ 30% change in MADRS score between screening and baseline
- Anyone presenting with:
- Mania or hypomania
- Psychosis
- Active suicidal ideation or a suicide attempt (defined by C-SSRS) within the past year
- Neurological lesion
- Contraindications to either TMS or MRI (e.g., metallic implants, severe insomnia > 4 hours per night with hypnotic, etc.).
- Current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal
- Positive urine drug screen for illicit substances
- Severe borderline personality disorder
- Any other condition deemed by the PI to interfere with the study or increase risk to the participant
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02115
About this study
Official title: The Role of Individualized Functional Connectivity Targeting in Accelerated Intelligent Neuromodulation Therapy (AINT) for Depression
The goal of this clinical trial is to estimate the importance of neuroimaging in accelerated intermittent theta burst stimulation (aiTBS) for depression. Participants will receive aiTBS treatment, but they will not know if their treatment spot was found with neuroimaging or head measurements.
Read the detailed description
Techniques for modulating human brain networks are rapidly evolving. One of the most exciting new developments is accelerated intermittent theta burst stimulation (aiTBS), a transcranial magnetic stimulation (TMS) protocol that involves multiple daily treatments rather than gold standard once daily treatment. A specific accelerated iTBS protocol called Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) was cleared by the FDA in September 2022 based on two pilot studies in which patients with treatment-resistant depression rapidly and robustly improved with SAINT. Many of these patients had been depressed for decades and had not improved with conventional TMS or electroconvulsive therapy. Despite these promising results, two issues may limit SAINT scalability: 1) SAINT has only been tested at a single site in a small number of patients, 2) SAINT has never been tested without individualized resting state functional connectivity (rsfc) targeting, which is not widely available or covered by insurance. In this pilot trial, patients with treatment-resistant depression (n=40) will be randomized to one of two active treatment arms: 1) Real aiTBS with real individualized rsfc targeting, or 2) Real aiTBS with sham individualized rsfc targeting (i.e. conventional TMS targeting based on scalp landmarks). All patients will receive active stimulation, which will facilitate enrollment and reduce ethical concerns about placebo treatment in a vulnerable population when there is existing evidence of treatment efficacy. Patients and clinicians will be blind to group assignment, and blind integrity will be assessed. All patients will undergo MRI scans immediately before treatment and at one month follow up, which aligns with our clinical outcome measures.
- Conditions
- Depressive Disorder, Major, Depression, Mood Disorders, Mental Disorder, Psychiatric Disorder
- Being tested
- transcranial magnetic stimulation
- Keywords
- transcranial magnetic stimulation, accelerated intermittent theta burst stimulation, theta burst stimulation, brain stimulation, neuromodulation, depression, transcranial, TMS, neuronavigation, functional connectivity, neuroimaging
- Medical subject headings
- Depressive Disorder, Major, Depression, Mood Disorders, Mental Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
transcranial magnetic stimulationProcedure or surgery
Also called TMS, theta burst stimulation, accelerated intermittent theta burst stimulation, aiTBS
Transcranial magnetic stimulation (TMS) is a focal, non-invasive form of brain stimulation that has FDA clearance for depression. In this study, a form of TMS called accelerated intermittent theta burst stimulation will be administered under the supervision of a physician with TMS expertise. This protocol will be modeled after the FDA cleared Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) protocol, but the patented SAINT rsfc targeting algorithm will not be used for either arm.
| Study group | Role | What they receive |
|---|---|---|
| real individualized resting state functional connectivity targeting | Other | Participants in this group will receive aiTBS with neuronavigation to a treatment target identified with individualized resting state functional connectivity. Receives: Procedure: transcranial magnetic stimulation |
| sham individualized resting state functional connectivity targeting | Other | Participants in this group will receive aiTBS with neuronavigation to a treatment target identified with head measurements (i.e., Beam F3) Receives: Procedure: transcranial magnetic stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Montgomery-Åsberg Depression Rating Scale (MADRS)
Depression severity rating scale (0-60, higher numbers indicate higher severity). The primary outcome measure was the baseline-adjusted MADRS score one month after treatment. The primary analysis of this primary outcome measure was the effect size of connectivity-based targeting.
Measured: Baseline, one month after treatment
Secondary outcomes (4)
Beck Depression Inventory (BDI)
Depression severity rating scales (0-63, higher numbers indicate higher severity)
Measured: Screening, Day 5 of Treatment, 1 Week Post Treatment, & 1 Month Post Treatment
Beck Anxiety Inventory (BAI)
Anxiety severity rating scale (0-63, higher numbers indicate higher severity)
Measured: Screening, Day 5 of Treatment, 1 Week Post Treatment, & 1 Month Post Treatment
Montgomery-Åsberg Depression Rating Scale (MADRS)
Depression severity rating scale (0-60, higher numbers indicate higher severity). The primary analysis of the primary outcome will be the effect size of imaging-guided accelerated TMS relative to scalp-targeted TMS. In other words, the "number needed to scan." This outcome has not changed since the original grant application for this study and the data remain blinded at the time of this clarification. Actual group differences will be explored in a secondary analysis of this primary outcome measure.
Measured: Baseline & 1 Month Post Treatment
Change in Resting State Functional Connectivity in the Depression Network
Blood oxygen level-dependent (BOLD) signal.
Measured: Baseline, one month after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2023
- Study start15 Jul 2023
- Primary completion17 Mar 2025
- Study completion17 Feb 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Depressive Disorder, MajorStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel-group double-blind randomized controlled trial
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Joseph J. Taylor, MD, PhD, Brigham and Women's Hospital
- Investigators
- Joseph J Taylor, MD, PhD, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05680727
- Sponsor's protocol ID
- 2022p001650
- Acronym
- AINT
- Status last verified
- May 2025
- First submitted
- 13 Dec 2022
- Last updated
- 25 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided: De-identified survey response data and/or neuroimaging data may be shared with collaborators for further analysis.
Publications
Taylor JJ, Kare MR, Haj-Darwish D, Jones E, Sanderson L, Khosravani S, Leach J, Bomer L, Hall N, Chiulli N, Steuber E, Lin C, Drew W, Palm ST, Chandra A, Frandsen SB, Bekou A, Barbour T, Baratono SR, Gonsalvez I, Lyndon S, Schaper FLWVJ, Wang W, Silbersweig D, Siddiqi SH, Fox MD. Connectivity- vs Scalp-Based Targeting of Accelerated Transcranial Magnetic Stimulation for Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2026 Aug 1;83(8):807-817. doi: 10.1001/jamapsychiatry.2026.1100.
PubMed 42340706
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Individualized Functional Connectivity Targeting in Accelerated Intelligent Neuromodulation Therapy (AINT) for Depression
- ClinicalTrials.gov ID
- NCT05680727
- Acronym / sponsor ID
- AINT / 2022p001650
- Conditions
- Depressive Disorder, Major, Depression, Mood Disorders, Mental Disorder, Psychiatric Disorder
- Keywords
- transcranial magnetic stimulation, accelerated intermittent theta burst stimulation, theta burst stimulation, brain stimulation, neuromodulation, depression, transcranial, TMS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- 15 Jul 2023 (actual)
- Primary completion
- 17 Mar 2025 (actual)
- Study completion
- 17 Feb 2026 (actual)
- First posted
- 11 Jan 2023 (actual)
- Results
- Posted 7 Jul 2026
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 estimate the importance of neuroimaging in accelerated intermittent theta burst stimulation (aiTBS) for depression. Participants will receive aiTBS treatment, but they will not know if their treatment spot was found with neuroimaging or head measurements.
Detailed description
Techniques for modulating human brain networks are rapidly evolving. One of the most exciting new developments is accelerated intermittent theta burst stimulation (aiTBS), a transcranial magnetic stimulation (TMS) protocol that involves multiple daily treatments rather than gold standard once daily treatment. A specific accelerated iTBS protocol called Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) was cleared by the FDA in September 2022 based on two pilot studies in which patients with treatment-resistant depression rapidly and robustly improved with SAINT. Many of these patients had been depressed for decades and had not improved with conventional TMS or electroconvulsive therapy. Despite these promising results, two issues may limit SAINT scalability: 1) SAINT has only been tested at a single site in a small number of patients, 2) SAINT has never been tested without individualized resting state functional connectivity (rsfc) targeting, which is not widely available or covered by insurance. In this pilot trial, patients with treatment-resistant depression (n=40) will be randomized to one of two active treatment arms: 1) Real aiTBS with real individualized rsfc targeting, or 2) Real aiTBS with sham individualized rsfc targeting (i.e. conventional TMS targeting based on scalp landmarks). All patients will receive active stimulation, which will facilitate enrollment and reduce ethical concerns about placebo treatment in a vulnerable population when there is existing evidence of treatment efficacy. Patients and clinicians will be blind to group assignment, and blind integrity will be assessed. All patients will undergo MRI scans immediately before treatment and at one month follow up, which aligns with our clinical outcome measures.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Parallel-group double-blind randomized controlled trial
| Arm | Type | Receives |
|---|---|---|
| real individualized resting state functional connectivity targeting | Other | Procedure: transcranial magnetic stimulationParticipants in this group will receive aiTBS with neuronavigation to a treatment target identified with individualized resting state functional connectivity. |
| sham individualized resting state functional connectivity targeting | Other | Procedure: transcranial magnetic stimulationParticipants in this group will receive aiTBS with neuronavigation to a treatment target identified with head measurements (i.e., Beam F3) |
Who may qualify
- Ages
- 22 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- English proficiency sufficient for informed consent, questionnaires/tasks, and treatment
- Primary diagnosis of major depressive disorder per Diagnostic and Statistical Manual (DSM)-V criteria (MINI International Neuropsychiatric Interview)
- >20 on BDI
- >20 on the MADRS 10, 11
- Moderate to severe level of treatment resistance (Maudsley Staging Method)
Key exclusion criteria (25 listed)
- Active pregnancy as determined by a urine pregnancy test
- Primary psychiatric diagnosis other than major depressive disorder requiring treatment other than comorbid anxiety disorder
- Those who did not respond to electroconvulsive therapy (ECT) after 8 sessions
- Recent (within 4 weeks) or concurrent use of rapid acting antidepressant agent (ketamine/esketamine/ECT)
- History of:
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 stimulationAlso: TMS, theta burst stimulation, accelerated intermittent theta burst stimulation, aiTBSTranscranial magnetic stimulation (TMS) is a focal, non-invasive form of brain stimulation that has FDA clearance for depression. In this study, a form of TMS called accelerated intermittent theta burst stimulation will be administered under the supervision of a physician with TMS expertise. This protocol will be modeled after the FDA cleared Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) protocol, but the patented SAINT rsfc targeting algorithm will not be used for either arm. | Procedure or surgery | real individualized resting state functional connectivity targeting, sham individualized resting state functional connectivity targeting |
Primary outcome
Montgomery-Åsberg Depression Rating Scale (MADRS)
Time frame: Baseline, one month after treatment
Depression severity rating scale (0-60, higher numbers indicate higher severity). The primary outcome measure was the baseline-adjusted MADRS score one month after treatment. The primary analysis of this primary outcome measure was the effect size of connectivity-based targeting.
4 secondary outcomes
Beck Depression Inventory (BDI)
Time frame: Screening, Day 5 of Treatment, 1 Week Post Treatment, & 1 Month Post Treatment
Beck Anxiety Inventory (BAI)
Time frame: Screening, Day 5 of Treatment, 1 Week Post Treatment, & 1 Month Post Treatment
Montgomery-Åsberg Depression Rating Scale (MADRS)
Time frame: Baseline & 1 Month Post Treatment
Change in Resting State Functional Connectivity in the Depression Network
Time frame: Baseline, one month after treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42340706Taylor JJ, Kare MR, Haj-Darwish D, Jones E, Sanderson L, Khosravani S, Leach J, Bomer L, Hall N, Chiulli N, Steuber E, Lin C, Drew W, Palm ST, Chandra A, Frandsen SB, Bekou A, Barbour T, Baratono SR, Gonsalvez I, Lyndon S, Schaper FLWVJ, Wang W, Silbersweig D, Siddiqi SH, Fox MD. Connectivity- vs Scalp-Based Targeting of Accelerated Transcranial Magnetic Stimulation for Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2026 Aug 1;83(8):807-817. doi: 10.1001/jamapsychiatry.2026.1100.
- 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. This study is not recruiting at the moment.
Joseph J Taylor, MD, PhD principal investigator
Brigham and Women's Hospital
1 site 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 Depressive Disorder, Major and Depression, run by Brigham and Women's Hospital 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 12 inclusion and 25 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 25 Aug 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 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?
Yes. Results are posted in the registry (first posted 7 Jul 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Montgomery-Åsberg Depression Rating Scale (MADRS) (time frame: Baseline, one month after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05680727, which also lists 1 linked publication.
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 25 Aug 2026.