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RecruitingNCT03276793Updated Apr 21, 2025

Brain Connectivity in Depression

An interventional study of MRI scan and Behavioral testing in Depression, sponsored by Brigham and Women's Hospital. Recruiting at 4 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-04-21.

Sponsored by Brigham and Women's Hospital · Not applicable, Interventional, and Basic science

Phase
Not applicable
Study type
Interventional
Enrollment
260
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

This study originally included 140 subjects with medication-refractory depression undergoing 10 Hz transcranial magnetic stimulation (10Hz-TMS) to the left dorsal lateral prefrontal cortex (DLPFC), with the goal of having 60 completers with good quality data. Subjects were recruited from the TMS clinics at Beth Israel Deaconess Medical Center, Brigham \& Women's Hospital, and Butler Hospital. Subjects underwent an hour-long MRI scanning session, an optional DNA-sample collection, up to three 20 minute neuronavigation sessions for marking the site of TMS stimulation, questionnaires, and a behavioral testing battery before and after their TMS treatment course. The task battery included the Emotion Conflict Resolution (ECR) task, Multi-Source Interference Task (MSIT), War Game (Gambling) task, and Associative Learning with Reversal task. Subjects' scores on the Quick Inventory of Depressive Symptomatology (QIDS) and Beck Depression Inventory (BDI) were assessed before and after the TMS course. MRI data was utilized to identify brain regions whose connectivity to the stimulation site co-varies with the aforementioned measures of symptom improvement. This was the only study group until August 30, 2022, and the primary outcome was analyzed for the 10Hz-TMS group.

Due to changes in clinical standard of care from 10Hz-TMS to a newer version of TMS termed intermittent theta burst (iTBS), in September 2022 a second group was added to include patients receiving this new form of TMS. This second group included another 100 patients with medication-refractory depression undergoing iTBS to the left dorsal lateral prefrontal cortex (DLPFC), with the intent to have 80 completers. Massachusetts General Hospital was added as a data collection site in lieu of Butler Hospital. Subjects will undergo an hour-long MRI scanning session, up to three 20 minute neuronavigation sessions for marking the site of TMS stimulation, questionnaires, and a behavioral testing battery before and after their TMS treatment course. The task battery will included the Emotion Conflict Resolution (ECR) task, Multi-Source Interference Task (MSIT), Penn Emotion Recognition Test, the Suicide/Death Implicit Association Test, and Associative Learning with Reversal task. Subjects' scores on the Beck Depression Inventory (BDI) were assessed before and after the TMS course. MRI data will be utilized to identify brain regions whose connectivity to the stimulation site co-varies with the aforementioned measures of symptom improvement.

Due to a higher dropout rate than anticipated, in March of 2025 an amendment was added to include an additional 20 subjects in the second group's enrollment goal to increase the likelihood of achieving 80 completers.

Read the detailed description

This study was originally approved by the Beth Israel Deaconess Medical Center (BIDMC) Institutional Review Board (IRB) with Butler Hospital as a relying site. The study was transferred to the Mass General Brigham (MGB) IRB in 2020 when Dr. Fox (lead PI) moved to Brigham and Women's Hospital (BWH). Butler Hospital continued to enroll subjects, relying on the MGB IRB for regulatory oversight, while BIDMC stopped enrolling subjects. A Data Usage Agreement was established between BIDMC and BWH, and all previously collected Data was de-identified and sent to BWH. The protocol at BIDMC will remain active but not enrolling until all the de-identified data has been sent to BWH.

In Sept 2022, with the launch of the second iTBS group, Massachusetts General Hospital replaced Butler Hospital as the secondary enrollment site, while enrollment continued at Brigham and Women's Hospital.

02

Conditions studied

03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Male or female
  2. Aged 18 or older
  3. Have previously received or will once daily TMS treatment to the left dorsolateral prefrontal cortex at the Center for Brain Circuit Therapeutics at Brigham and Women's Hospital, or at Massachusetts General Hospital for treatment of medication resistant depression

Exclusion criteria

Exclusion Criteria:

  1. Presence of a significant neurologic disorder (i.e. Parkinson's Disease, stroke, Alzheimer's Disease, tumor, multiple sclerosis, epilepsy) or other significant active medical problems which may impact treatment or safety. Of note, many of these are also contraindications to receiving TMS and these patients would not be enrolled in the clinical treatment program. Because these diagnoses, their significance, and the extent to which they are an active issue can be subjective, each of these exclusions (1-3) will be reviewed by the PI or study physician
  2. Lack of response to an adequate trial of electroconvulsive therapy (ECT) or any ECT in the preceding 3 months
  3. Prior adequate trial of TMS treatment in the last 12 months
  4. Positive MRI screen that would preclude the subject from undergoing magnetic resonance imaging. These include, but are not limited to any of the following:

    1. Known metal in the head (such as a surgical aneurysm clip), or a history of prior neurosurgical procedures
    2. Ferromagnetic bioimplants activated by any electronic, mechanical or magnetic means such as: cochlear implants, pacemakers, medication pumps, vagal stimulators, deep brain stimulators, neurostimulators, biostimulators, or ventriculo-peritoneal shunts
    3. Subjects who have or might have bullet fragments or other metal fragments (veterans or workers exposed to metal in their work environment)
    4. Subjects with metallic paint (e.g. color contact lenses, tattoos, metallic eyeliner)
    5. Subjects expressing significant anxiety or claustrophobia about being in the magnet.
  5. Subjects that cannot adhere to the experimental protocol for any reason.
04

Study design

Phase
Not applicable
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
260 participants (estimated)

Study arms

  • Experimental
    MRI and behavioral assessment for patients receiving TMS

    Subjects will undergo an hour-long MRI scanning session, a marking for the site of planned clinical TMS stimulation and a behavioral testing battery before and after their TMS treatment course.

    Other: MRI scan · Behavioral: Behavioral testing

Interventions

  • OtherMRI scan

    Patients will undergo an MRI scan

  • BehavioralBehavioral testing

    Patients will complete a series of cognitive tasks

05

What researchers measure

Primary outcomes

  1. Prediction of repetitive Transcranial Magnetic Stimulation (rTMS) clinical response

    Connectivity between each patient's stimulation site and the subgenual cingulate will be used to predict clinical response to rTMS in the first group (data collected starting in 2017).

    Time frame: 1 year after study completion

  2. Prediction of intermittent theta burst stimulation (iTBS) clinical response

    Normative connectivity of each patient's stimulation site to a previously-published "depression network" (Siddiqi et al., Nat Hum Behav 2021) will be used to predict clinical response to iTBS in the second group added in September 2022.

    Time frame: 1 year after study completion

06

Study locations

2 of 4 sites recruiting
  • Brigham and Women's Hospital
    Boston, Massachusetts 02115, United States
    • Michael D Fox, MD, PhD · Contact · bwh_fdctrial@mgb.org · 617-732-7432
    • Michael D Fox, MD, PhD · Principal investigator
    • Joseph J Taylor, MD, PhD · Sub investigator
    • Shan H Siddiqi, MD · Sub investigator
    • Stephan T Palm, BS · Sub investigator
    • Christopher Lin, BS · Sub investigator
    • Dania Haj-Darwish, BS · Sub investigator
    • Summer B Frandsen, BS · Sub investigator
    • William Drew, BA · Sub investigator
    • Sanaz Khosravani, PhD · Sub investigator
    • David W Lawson, BA · Sub investigator
    • Emma Jones, BS · Sub investigator
    Recruiting
  • Massachusetts General Hospital
    Boston, Massachusetts 02129, United States
    • Tracy A Barbour, MD · Contact · TBARBOUR@PARTNERS.ORG · 617-726-5340
    • Luke Janak, BS · Contact · Ljanak@mgh.harvard.edu
    • Tracy A Barbour, MD · Principal investigator
    • Joan A Camprodon, MD, MPH, PhD · Principal investigator
    • Nicole L Brocious, BS · Sub investigator
    • Christopher J Funes, MS · Sub investigator
    • James R Coleman, BS · Sub investigator
    • Anna Moser, MS · Sub investigator
    • Olivia J Newman, BS · Sub investigator
    • Astrid Warney, MS · Sub investigator
    • Stephanie R Kramer, BS · Sub investigator
    Recruiting
  • Beth Israel Deaconess Medical Center
    Boston, Massachusetts 02215, United States
    Completed
  • Butler Hospital
    Providence, Rhode Island 02906, United States
    Active, not recruiting
07

References and documents

Individual participant data

Plan to share: Undecided

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03276793
Lead sponsor
Brigham and Women's Hospital
Collaborators
Butler Hospital, Massachusetts General Hospital, National Institute of Mental Health (NIMH)
Responsible party
Michael D. Fox, M.D.,Ph.D. (Associate Professor, Brigham and Women's Hospital) — Principal investigator
First posted
Sep 8, 2017
Start date
Apr 3, 2018
Primary completion
Sep 30, 2027 (estimated)
Completion
Oct 31, 2027 (estimated)
Last update
Apr 21, 2025

Study contacts

David Lawson, BA
Contact
bwh_fdctrial@mgb.org
617-732-6658
Emma Jones, BS
Contact
bwh_fdctrial@mgb.org

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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