Individualized Functional Connectivity Targeting in aiTBS for Depression (AINT)
August 4, 2026 updated by: Joseph J. Taylor, MD, PhD, Brigham and Women's Hospital
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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 Type
Interventional
Enrollment (Actual)
40
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Massachusetts
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Boston, Massachusetts, United States, 02115
- Brigham and Women's Hospital
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
22 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- 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).
- 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
Exclusion Criteria:
- 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
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Other: real individualized resting state functional connectivity targeting
Participants in this group will receive aiTBS with neuronavigation to a treatment target identified with individualized resting state functional connectivity.
|
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.
Other Names:
|
|
Other: sham individualized resting state functional connectivity targeting
Participants in this group will receive aiTBS with neuronavigation to a treatment target identified with head measurements (i.e., Beam F3)
|
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
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.
|
Baseline, one month after treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Beck Depression Inventory (BDI)
Time Frame: Screening, Day 5 of Treatment, 1 Week Post Treatment, & 1 Month Post Treatment
|
Depression severity rating scales (0-63, higher numbers indicate higher severity)
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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
|
Anxiety severity rating scale (0-63, higher numbers indicate higher severity)
|
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
|
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.
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Baseline & 1 Month Post Treatment
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Change in Resting State Functional Connectivity in the Depression Network
Time Frame: Baseline, one month after treatment
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Blood oxygen level-dependent (BOLD) signal.
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Baseline, one month after treatment
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Temperament and Character Inventory, Revised 140-item
Time Frame: Baseline, one month after treatment
|
Psychobiologically-based personality inventory which measures seven personality dimensions (harm avoidance, novelty seeking, reward dependence, persistence, self-directedness, cooperativeness, and persistence).
For each dimension, this yields a scaled T-score (mean score of 50 with standard deviation of 10).
This is an overall estimate of personality traits, and there are no "better" or "worse" traits.
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Baseline, one month after treatment
|
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Emotional Conflict Resolution Task
Time Frame: Baseline, one month after treatment
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Computer task measuring accuracy and reaction time
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Baseline, one month after treatment
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Learning, Multi-Source Interference Task (MSIT)
Time Frame: Baseline, one month after treatment
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Computer task measuring accuracy and reaction time
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Baseline, one month after treatment
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Penn Emotion Recognition Task (ER-40)
Time Frame: Baseline, one month after treatment
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Computer task measuring accuracy and reaction time
|
Baseline, one month after treatment
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Death Suicide IAT (DSIAT)
Time Frame: Baseline, one month after treatment
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Computer task measuring reaction time
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Baseline, one month after treatment
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Joseph J Taylor, MD, PhD, Brigham and Women's Hospital
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
July 15, 2023
Primary Completion (Actual)
March 17, 2025
Study Completion (Actual)
February 17, 2026
Study Registration Dates
First Submitted
December 13, 2022
First Submitted That Met QC Criteria
January 10, 2023
First Posted (Actual)
January 11, 2023
Study Record Updates
Last Update Posted (Actual)
August 25, 2026
Last Update Submitted That Met QC Criteria
August 4, 2026
Last Verified
May 1, 2025
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2022p001650
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
IPD Plan Description
De-identified survey response data and/or neuroimaging data may be shared with collaborators for further analysis.
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
Yes
product manufactured in and exported from the U.S.
Yes
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