Brain Connectivity in Depression

NCT ID: NCT03276793

Last Updated: 2025-04-21

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 260 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-03
• Study Completion Date: 2027-10-31

Brief 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.

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.

Conditions

Depression

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

MRI scan

Intervention Type: OTHER

Patients will undergo an MRI scan

Behavioral testing

Intervention Type: BEHAVIORAL

Patients will complete a series of cognitive tasks

Interventions

MRI scan

Patients will undergo an MRI scan

Intervention Type: OTHER

Behavioral testing

Patients will complete a series of cognitive tasks

Intervention Type: BEHAVIORAL

Eligibility Criteria

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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Butler Hospital

OTHER

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Michael D. Fox, M.D.,Ph.D.

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status: COMPLETED

Butler Hospital

Providence, Rhode Island, United States

Site Status: ACTIVE_NOT_RECRUITING

Countries

United States

Central Contacts

David Lawson, BA

Role: CONTACT

bwh_fdctrial@mgb.org

617-732-6658

Emma Jones, BS

Role: CONTACT

bwh_fdctrial@mgb.org

Facility Contacts

Michael D Fox, MD, PhD

Role: primary

bwh_fdctrial@mgb.org

617-732-7432

Tracy A Barbour, MD

Role: primary

TBARBOUR@PARTNERS.ORG

617-726-5340

Luke Janak, BS

Role: backup

Ljanak@mgh.harvard.edu

References

Khosravani S, Palm ST, Drew W, Frandsen SB, Lin C, Tirrell E, Hindley L, Schineller M, Garimella A, Chiulli N, Lawson D, Jones E, Press DZ, Stern AP, Brown JC, Barbour TA, Taylor JJ, Carpenter LL, Siddiqi SH, Fox MD. Predictive value of subgenual cingulate normative connectivity to TMS treatment site for antidepressant response in routine clinical practice: a prospective, multisite cohort study. Mol Psychiatry. 2025 Aug 22. doi: 10.1038/s41380-025-03153-3. Online ahead of print.

Reference Type: DERIVED

PMID: 40847007 (View on PubMed)

Other Identifiers

R01MH113929

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2021P000335

Identifier Type: -

Identifier Source: org_study_id