Trial Outcomes & Findings for Individualized Functional Connectivity Targeting in aiTBS for Depression (NCT NCT05680727)
NCT ID: NCT05680727
Last Updated: 2026-07-07
Results Overview
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.
COMPLETED
PHASE2
40 participants
Baseline, one month after treatment
2026-07-07
Participant Flow
Recruitment ran July 2023-March 2025. Recruitment sources included Rally, Mass General Brigham outpatient clinics/healthcare providers, and clinicaltrials.gov. Additionally, flyers were posted around the greater Mass General Brigham area.
A total of 40 participants were assigned to either a connectivity-based target or scalp-based target. Participants were ineligible after screening due to the following reasons: not meeting depression threshold cutoffs (\<20 BDI/MADRS \& mild Maudsley Staging Method) defined by inclusion criteria, history of tinnitus (ringing in the ears), symptoms of post-traumatic stress disorder, risk of seizure, active symptoms of substance use disorder, and history of brain tumor.
Participant milestones
| Measure |
Connectivity-based Targeting
Participants in this group received high-dose accelerated TMS with neuronavigation to a connectivity-based target, which was defined as the left dorsolateral prefrontal cortex region with the greatest correlation to a published and publicly available convergent depression circuit. This circuit includes multiple brain regions causally linked to depression, including negative connectivity to the subgenual cingulate cortex.
|
Scalp-based Targeting
Participants in this group received aiTBS with neuronavigation to a treatment target identified with with the Beam F3 method.
|
|---|---|---|
|
Overall Study
STARTED
|
20
|
20
|
|
Overall Study
COMPLETED
|
20
|
20
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Individualized Functional Connectivity Targeting in aiTBS for Depression
Baseline characteristics by cohort
| Measure |
Total
n=40 Participants
Total of all reporting groups
|
Connectivity-based Targeting
n=20 Participants
Participants in this group received high-dose aTMS with neuronavigation to a connectivity-based target, which was defined as the left dorsolateral prefrontal cortex region with the greatest correlation to a published and publicly available convergent depression circuit. This circuit includes multiple brain regions causally linked to depression, including negative connectivity to the subgenual cingulate cortex.
|
Scalp-based Targeting
n=20 Participants
Participants in this group received high-dose aTMS with neuronavigation to a treatment target identified with the Beam F3 method.
|
|---|---|---|---|
|
Age, Customized
Age (Mean, SD)
|
45.70 Years
STANDARD_DEVIATION 15.18 • n=40 Participants
|
42.95 Years
STANDARD_DEVIATION 14.24 • n=20 Participants
|
48.45 Years
STANDARD_DEVIATION 15.95 • n=20 Participants
|
|
Sex/Gender, Customized
Female
|
22 Participants
n=40 Participants
|
12 Participants
n=20 Participants
|
10 Participants
n=20 Participants
|
|
Sex/Gender, Customized
Male
|
18 Participants
n=40 Participants
|
8 Participants
n=20 Participants
|
10 Participants
n=20 Participants
|
|
Race/Ethnicity, Customized
White
|
29 Participants
n=40 Participants
|
13 Participants
n=20 Participants
|
16 Participants
n=20 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
1 Participants
n=40 Participants
|
1 Participants
n=20 Participants
|
0 Participants
n=20 Participants
|
|
Race/Ethnicity, Customized
Asian
|
5 Participants
n=40 Participants
|
3 Participants
n=20 Participants
|
2 Participants
n=20 Participants
|
|
Race/Ethnicity, Customized
Multiracial
|
4 Participants
n=40 Participants
|
3 Participants
n=20 Participants
|
1 Participants
n=20 Participants
|
|
Race/Ethnicity, Customized
Unknown/not reported
|
1 Participants
n=40 Participants
|
0 Participants
n=20 Participants
|
1 Participants
n=20 Participants
|
PRIMARY outcome
Timeframe: Baseline, one month after treatmentDepression 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.
Outcome measures
| Measure |
Connectivity-based Targeting
n=20 Participants
Participants in this group received aiTBS with neuronavigation to a connectivity-based target. The connectivity-based target was defined as the left dorsolateral prefrontal cortex region with the greatest correlation to a published and publicly available convergent depression circuit. This circuit includes multiple brain regions causally linked to depression, including negative connectivity to the subgenual cingulate cortex.
|
Scalp-based Targeting
n=20 Participants
Participants in this group received aiTBS with neuronavigation to a treatment target identified with with the Beam F3 method.
|
|---|---|---|
|
Montgomery-Åsberg Depression Rating Scale (MADRS)
Baseline
|
35 Scores on scale
Interval 28.0 to 38.25
|
31 Scores on scale
Interval 26.0 to 33.25
|
|
Montgomery-Åsberg Depression Rating Scale (MADRS)
1 Month
|
6 Scores on scale
Interval 1.5 to 12.5
|
11 Scores on scale
Interval 4.0 to 22.0
|
SECONDARY outcome
Timeframe: Screening, Day 5 of Treatment, 1 Week Post Treatment, & 1 Month Post TreatmentDepression severity rating scales (0-63, higher numbers indicate higher severity)
Outcome measures
| Measure |
Connectivity-based Targeting
n=20 Participants
Participants in this group received aiTBS with neuronavigation to a connectivity-based target. The connectivity-based target was defined as the left dorsolateral prefrontal cortex region with the greatest correlation to a published and publicly available convergent depression circuit. This circuit includes multiple brain regions causally linked to depression, including negative connectivity to the subgenual cingulate cortex.
|
Scalp-based Targeting
n=20 Participants
Participants in this group received aiTBS with neuronavigation to a treatment target identified with with the Beam F3 method.
|
|---|---|---|
|
Beck Depression Inventory (BDI)
Screening
|
37 Scores on scale
Interval 26.0 to 44.5
|
28.50 Scores on scale
Interval 23.0 to 34.5
|
|
Beck Depression Inventory (BDI)
Day 5 of Treatment
|
11.50 Scores on scale
Interval 7.0 to 31.5
|
13.50 Scores on scale
Interval 10.0 to 17.0
|
|
Beck Depression Inventory (BDI)
1 Week Post Treatment
|
8 Scores on scale
Interval 1.5 to 25.5
|
10 Scores on scale
Interval 6.0 to 18.0
|
|
Beck Depression Inventory (BDI)
1 Month Post Treatment
|
10 Scores on scale
Interval 2.0 to 22.0
|
10.00 Scores on scale
Interval 5.0 to 17.5
|
SECONDARY outcome
Timeframe: Screening, Day 5 of Treatment, 1 Week Post Treatment, & 1 Month Post TreatmentPopulation: Delay in measure's data collection contributing to a total of 11 participants not completing the BAI at screening.
Anxiety severity rating scale (0-63, higher numbers indicate higher severity)
Outcome measures
| Measure |
Connectivity-based Targeting
n=17 Participants
Participants in this group received aiTBS with neuronavigation to a connectivity-based target. The connectivity-based target was defined as the left dorsolateral prefrontal cortex region with the greatest correlation to a published and publicly available convergent depression circuit. This circuit includes multiple brain regions causally linked to depression, including negative connectivity to the subgenual cingulate cortex.
|
Scalp-based Targeting
n=12 Participants
Participants in this group received aiTBS with neuronavigation to a treatment target identified with with the Beam F3 method.
|
|---|---|---|
|
Beck Anxiety Inventory (BAI)
Screening
|
15 Scores on scale
Interval 5.5 to 19.0
|
19 Scores on scale
Interval 12.5 to 31.0
|
|
Beck Anxiety Inventory (BAI)
Day 5 of Treatment
|
0 Scores on scale
Interval 0.0 to 3.25
|
3 Scores on scale
Interval 2.0 to 4.0
|
|
Beck Anxiety Inventory (BAI)
1 Week Post Treatment
|
0 Scores on scale
Interval 0.0 to 4.0
|
2.50 Scores on scale
Interval 2.0 to 6.0
|
|
Beck Anxiety Inventory (BAI)
1 Month Post Treatment
|
1 Scores on scale
Interval 0.0 to 5.5
|
3 Scores on scale
Interval 2.0 to 5.0
|
SECONDARY outcome
Timeframe: Baseline & 1 Month Post TreatmentPopulation: This secondary outcome was not analyzed.
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.
Outcome measures
| Measure |
Connectivity-based Targeting
n=20 Participants
Participants in this group received aiTBS with neuronavigation to a connectivity-based target. The connectivity-based target was defined as the left dorsolateral prefrontal cortex region with the greatest correlation to a published and publicly available convergent depression circuit. This circuit includes multiple brain regions causally linked to depression, including negative connectivity to the subgenual cingulate cortex.
|
Scalp-based Targeting
n=20 Participants
Participants in this group received aiTBS with neuronavigation to a treatment target identified with with the Beam F3 method.
|
|---|---|---|
|
Montgomery-Åsberg Depression Rating Scale (MADRS)
Baseline
|
36 Scores on scale
Interval 28.0 to 38.25
|
31 Scores on scale
Interval 26.0 to 33.25
|
|
Montgomery-Åsberg Depression Rating Scale (MADRS)
1 Month Post Treatment
|
6 Scores on scale
Interval 1.5 to 12.5
|
11 Scores on scale
Interval 2.0 to 22.0
|
SECONDARY outcome
Timeframe: Baseline, one month after treatmentBlood oxygen level-dependent (BOLD) signal.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, one month after treatmentDepression severity rating scales (0-27, higher numbers indicate higher severity)
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, one month after treatmentPsychobiologically-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.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, one month after treatmentPopulation: This pre-specified outcome was not analyzed.
Computer task measuring accuracy and reaction time
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, one month after treatmentPopulation: This pre-specified outcome was not analyzed.
Computer task measuring accuracy and reaction time
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, one month after treatmentPopulation: This pre-specified outcome was not analyzed.
Computer task measuring accuracy and reaction time
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, one month after treatmentPopulation: This pre-specified outcome was not analyzed.
Computer task measuring reaction time
Outcome measures
Outcome data not reported
Adverse Events
Connectivity-based Targeting
Scalp-based Targeting
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Connectivity-based Targeting
n=20 participants at risk
Participants in this group received high-dose aTMS with neuronavigation to a connectivity-based target, which was defined as the left dorsolateral prefrontal cortex region with the greatest correlation to a published and publicly available convergent depression circuit. This circuit includes multiple brain regions causally linked to depression, including negative connectivity to the subgenual cingulate cortex.
|
Scalp-based Targeting
n=20 participants at risk
Participants in this group received high-dose aTMS with neuronavigation to a treatment target identified with the Beam F3 method.
|
|---|---|---|
|
General disorders
Scalp discomfort
|
45.0%
9/20 • Day 1 to day 5 of treatment
|
65.0%
13/20 • Day 1 to day 5 of treatment
|
|
Nervous system disorders
Headache
|
25.0%
5/20 • Day 1 to day 5 of treatment
|
55.0%
11/20 • Day 1 to day 5 of treatment
|
|
Nervous system disorders
Face twitching/tingling
|
25.0%
5/20 • Day 1 to day 5 of treatment
|
25.0%
5/20 • Day 1 to day 5 of treatment
|
|
Ear and labyrinth disorders
Tinnitus (ringing in the ears)
|
20.0%
4/20 • Day 1 to day 5 of treatment
|
10.0%
2/20 • Day 1 to day 5 of treatment
|
|
Psychiatric disorders
Worsening symptoms of depression
|
15.0%
3/20 • Day 1 to day 5 of treatment
|
10.0%
2/20 • Day 1 to day 5 of treatment
|
|
Psychiatric disorders
Worsening symptoms of anxiety
|
30.0%
6/20 • Day 1 to day 5 of treatment
|
10.0%
2/20 • Day 1 to day 5 of treatment
|
|
Psychiatric disorders
Suicidal Ideation
|
5.0%
1/20 • Day 1 to day 5 of treatment
|
5.0%
1/20 • Day 1 to day 5 of treatment
|
Additional Information
Joseph J. Taylor, MD, PhD
Brigham & Women's Hospital, Mass General Brigham
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place