Individualized Functional Connectivity Targeting in aiTBS for Depression

NCT05680727 | Active Not Recruiting Phase 2 FDA Device

• 1 other identifier: 2022p001650
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

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; neuronavigation; functional connectivity; neuroimaging

Outcome Measures

Primary Outcomes (1)

• 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 (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.

  one month after treatment

Secondary Outcomes (11)

• Montgomery-Åsberg Depression Rating Scale (MADRS)

  immediately after treatment ends

• Beck Depression Inventory (BDI)

  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)

  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

  one month after treatment

• Percentage of screened patients from TMS clinical programs who select the accelerated iTBS trial over routine clinical TMS

  through study completion, an average of 2 years

Study Arms (2)

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.

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)

Procedure: transcranial magnetic stimulation

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.

Also known as: TMS, theta burst stimulation, accelerated intermittent theta burst stimulation, aiTBS

real individualized resting state functional connectivity targeting; sham individualized resting state functional connectivity targeting

Eligibility Criteria

• Age: 22 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Depression; Mood Disorders; Mental Disorders

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Depressive Disorder; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Joseph J Taylor, MD, PhD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants will put on a swim cap and undergo treatment site-marking according to standard protocols. All individuals will get two treatment sites marked: 1) Their individualized target based on resting state functional connectivity data, and 2) Beam F3 target based on head measurements. One group will be treated at target #1, and the other group will be treated at target #2. Neither group will be able to see the computer screen that shows the neuronavigation in real-time, although they will be able to see their MRI scan on a monitor.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director of TMS

Model Details: Parallel-group double-blind randomized controlled trial

Study Record Dates

• First Submitted: December 13, 2022
• First Posted: January 11, 2023
• Study Start: July 15, 2023
• Primary Completion: March 17, 2025
• Study Completion (Estimated): March 17, 2027
• Last Updated: May 29, 2025

Record last verified: 2025-05

Locations

US (1)