---
title: Individualized Functional Connectivity Targeting in aiTBS for Depression
nct_id: NCT05680727
overall_status: ACTIVE_NOT_RECRUITING
phase: PHASE2
sponsor: "Brigham and Women's Hospital"
study_type: INTERVENTIONAL
primary_condition: Depressive Disorder, Major
countries: United States
canonical_url: "https://parkinsonspathways.com/agent/trials/NCT05680727.md"
clinicaltrials_gov: "https://clinicaltrials.gov/study/NCT05680727"
ct_last_update_post_date: 2025-05-29
last_seen_at: "2026-05-12T06:16:51.585Z"
source: ClinicalTrials.gov (mirrored, no enrichment)
---
# Individualized Functional Connectivity Targeting in aiTBS for Depression

**Official Title:** The Role of Individualized Functional Connectivity Targeting in Accelerated Intelligent Neuromodulation Therapy (AINT) for Depression

**NCT ID:** [NCT05680727](https://clinicaltrials.gov/study/NCT05680727)

## Key Facts

- **Status:** ACTIVE_NOT_RECRUITING
- **Phase:** PHASE2
- **Study Type:** INTERVENTIONAL
- **Target Enrollment:** 40
- **Lead Sponsor:** Brigham and Women's Hospital
- **Conditions:** Depressive Disorder, Major, Depression, Mood Disorders, Mental Disorder, Psychiatric Disorder
- **Start Date:** 2023-07-15
- **Completion Date:** 2027-03-17
- **CT.gov Last Update:** 2025-05-29

## Brief 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.

## 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.

## Eligibility

- **Minimum age:** 22 Years
- **Maximum age:** 80 Years
- **Sex:** ALL
- **Healthy Volunteers:** No

```
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
```

## Arms

- **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.
- **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)

## Interventions

- **transcranial magnetic stimulation** (PROCEDURE) — 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.

## Primary Outcomes

- **Montgomery-Åsberg Depression Rating Scale (MADRS)** _(time frame: one month after treatment)_ — Depression severity rating scale (0-60, higher numbers indicate higher severity). The primary analysis of the primary outcome will be the effect size (i.e., Cohen's d) of imaging-guided accelerated TMS relative to scalp-targeted TMS. This outcome has not changed since the original grant application for this study. Actual group differences will be explored in a secondary analysis of this primary outcome measure.

Note added May 2025: The description of the primary outcome measure was clarified. The primary outcome remains unchanged.

## Secondary Outcomes

- **Montgomery-Åsberg Depression Rating Scale (MADRS)** _(time frame: immediately after treatment ends)_
- **Beck Depression Inventory (BDI)** _(time frame: immediately after treatment ends and at all subsequent timepoints (1 week, 1 month, 3 months, 6 months, 9 months, 12 months))_
- **Quick Inventory of Depressive Symptomatology (QIDS)** _(time frame: immediately after treatment ends and at all subsequent timepoints (1 week, 1 month, 3 months, 6 months, 9 months, 12 months))_
- **Change in resting state functional connectivity in the depression network** _(time frame: one month after treatment)_
- **Percentage of screened patients from TMS clinical programs who select the accelerated iTBS trial over routine clinical TMS** _(time frame: through study completion, an average of 2 years)_
- **Temperament and Character Inventory, Revised 140-item** _(time frame: one month after treatment)_
- **Emotional Conflict Resolution Task** _(time frame: one month after treatment)_
- **Learning, Multi-Source Interference Task (MSIT)** _(time frame: one month after treatment)_
- **Penn Emotion Recognition Task (ER-40)** _(time frame: one month after treatment)_
- **Death Suicide IAT (DSIAT)** _(time frame: one month after treatment)_
- **Beck Anxiety Inventory (BAI)** _(time frame: immediately after treatment ends and at all subsequent timepoints (1 week, 1 month, 3 months, 6 months, 9 months, 12 months))_

## Locations (1)

- Brigham and Women's Hospital, Boston, Massachusetts, United States

## Recent Field Changes (last 30 days)

- `status.primaryCompletionDate` — added _(2026-05-12)_
- `status.completionDate` — added _(2026-05-12)_
- `status.lastUpdatePostDate` — added _(2026-05-12)_
- `design.phases` — added _(2026-05-12)_
- `design.enrollmentCount` — added _(2026-05-12)_
- `eligibility.criteria` — added _(2026-05-12)_
- `eligibility.minAge` — added _(2026-05-12)_
- `eligibility.maxAge` — added _(2026-05-12)_
- `eligibility.sex` — added _(2026-05-12)_
- `status.overallStatus` — added _(2026-05-12)_
- `outcomes.primary` — added _(2026-05-12)_
- `outcomes.secondary` — added _(2026-05-12)_
- `armsInterventions.arms` — added _(2026-05-12)_
- `armsInterventions.interventions` — added _(2026-05-12)_
- `sponsor.lead` — added _(2026-05-12)_
- `results.hasResults` — added _(2026-05-12)_
- `locations.brigham and women's hospital|boston|massachusetts|united states` — added _(2026-05-12)_

---

*Canonical: https://parkinsonspathways.com/agent/trials/NCT05680727.md*  
*Source data (authoritative): https://clinicaltrials.gov/study/NCT05680727*  
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