Brain Connectivity in Depression

August 7, 2023 updated by: Michael D. Fox, M.D.,Ph.D., Brigham and Women's Hospital

Using Human Brain Connectivity to Identify the Causal Neuroanatomical Substrate of Depression Symptoms

This study originally included 100 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.

Study Overview

Status

Recruiting

Conditions

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.

Study Type

Interventional

Enrollment (Estimated)

200

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Recruiting
        • Brigham and Women's Hospital
        • Contact:
        • Principal Investigator:
          • Michael D Fox, MD, PhD
        • Sub-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, BS
        • Sub-Investigator:
          • Sanaz Khosravani, PhD
      • Boston, Massachusetts, United States, 02215
        • Completed
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02129
        • Recruiting
        • Massachusetts General Hospital
        • Contact:
        • Principal Investigator:
          • Tracy A Barbour, MD
        • Principal Investigator:
          • Joan A Camprodon, MD, MPH, PhD
        • Sub-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
        • Contact:
        • Sub-Investigator:
          • Stephanie R Kramer, BS
    • Rhode Island
      • Providence, Rhode Island, United States, 02906
        • Active, not recruiting
        • Butler Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Male or female
  2. Aged 18-70.
  3. Have previously received or will receive TMS to the left dorsal-lateral prefrontal cortex as part of the clinical treatment program 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. History of bipolar disorder (lifetime), schizophrenia or psychosis (lifetime), obsessive-compulsive disorder (unstable in past six months), posttraumatic stress disorder (unstable in past six months), eating disorders (unstable in past six months), or moderate to severe substance use disorders (currently active, with the exception of nicotine and cannabis)
  2. Presence of a significant neurologic disorder (i.e. Parkinson's Disease, stroke, Alzheimer's Disease, tumor, multiple sclerosis, epilepsy). Of note, many of these are also contraindications to receiving TMS and these patients would not be enrolled in the clinical treatment program.
  3. Patients who are pregnant or lactating (by menstrual history)
  4. Current abuse of an illicit substance (e.g. marijuana, cocaine, heroin, hallucinogens, psychostimulants)
  5. 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.
  6. Subjects that cannot adhere to the experimental protocol for any reason.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Patients will undergo an MRI scan
Patients will complete a series of cognitive tasks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prediction of repetitive Transcranial Magnetic Stimulation (rTMS) clinical response
Time Frame: 1 year after study completion
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).
1 year after study completion
Prediction of intermittent theta burst stimulation (iTBS) clinical response
Time Frame: 1 year after study completion
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.
1 year after study completion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 3, 2018

Primary Completion (Estimated)

September 30, 2027

Study Completion (Estimated)

October 31, 2027

Study Registration Dates

First Submitted

September 5, 2017

First Submitted That Met QC Criteria

September 7, 2017

First Posted (Actual)

September 8, 2017

Study Record Updates

Last Update Posted (Actual)

August 9, 2023

Last Update Submitted That Met QC Criteria

August 7, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Other Study ID Numbers

  • 2021P000335
  • R01MH113929 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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