Brain Connectivity in Depression

• ClinicalTrials.gov Identifier: NCT03276793
• Recruitment Status: Recruiting
• First Posted: September 8, 2017
• Last Update Posted: May 18, 2022
• Sponsor: Brigham and Women's Hospital
• Collaborator: Butler Hospital
• Information provided by (Responsible Party): Michael D. Fox, M.D.,Ph.D., Brigham and Women's Hospital

Study Description

Brief Summary:

This study will include 60 subjects with medication-refractory depression undergoing transcranial magnetic stimulation (TMS) to the left dorsal lateral prefrontal cortex (DLPFC). In order to obtain good quality data and account for attrition, 100 subjects will be recruited. Subjects will be recruited from the Clinical Program of FDA approved TMS at the Center for Brain Circuit Therapeutics TMS Clinic and the Butler TMS Clinic. Subjects will undergo 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 will last 45-60 minutes and consist of 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) will also be 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 objective measures of symptom improvement.

Condition or disease	Intervention/treatment	Phase
Depression	Other: MRI scan; Behavioral: Behavioral testing	Not Applicable

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 is now transferred to the Mass General Brigham (MGB) IRB so that Dr. Fox, as the lead PI, can continue to provide oversight as his primary appointment is now at Brigham and Women's Hospital (BWH). Butler Hospital is now relying on the MGB IRB for regulatory oversight and will also be conducting all study procedures, while BIDMC will not become a relying site and will stop enrolling subjects. A Data Usage Agreement is established between BIDMC and BWH, and all previously collected Data will be 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Using Human Brain Connectivity to Identify the Causal Neuroanatomical Substrate of Depression Symptoms
• Actual Study Start Date: April 3, 2018
• Estimated Primary Completion Date: October 31, 2022
• Estimated Study Completion Date: October 31, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: MRI and behavioral assessment; 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; Patients will undergo an MRI scan; Behavioral: Behavioral testing; Patients will complete a series of cognitive tasks

Outcome Measures

Primary Outcome Measures :

1. 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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 Butler Hospital for treatment of medication resistant depression

Exclusion Criteria:

1. Any current or past history of a major psychiatric illness other than depression and anxiety (e.g. bipolar affective disorder, schizophrenia, obsessive compulsive disorder, post-traumatic stress disorder, generalized anxiety disorder)
2. Any significant current neurological illness (e.g. a history of seizures or unexplained loss of consciousness, a family history of epilepsy, signs of increased intracranial pressure, previously abnormal MRI scans, parkinsonism or dementia). Of note, most 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.

Contacts and Locations

Contacts

Contact: Stephan Palm, BS; 617-732-6658; spalm1@bwh.harvard.edu

Contact: Christopher Lin, BS; clin@bwh.harvard.edu

Locations

United States, Massachusetts

Brigham and Women's Hospital; Recruiting

Boston, Massachusetts, United States, 02115

Contact: Michael D Fox, MD, PhD 617-732-7432 mdfox@bwh.harvard.edu

Sub-Investigator: Sandrine Jabbour, BS

Principal Investigator: Michael D Fox, MD, PhD

Sub-Investigator: Joseph J Taylor, MD, PhD

Sub-Investigator: Claudia Becker, BS

Sub-Investigator: Jing Li, BS

Sub-Investigator: Christopher Lin, BS

Beth Israel Deaconess Medical Center; Active, not recruiting

Boston, Massachusetts, United States, 02215

United States, Rhode Island

Butler Hospital; Recruiting

Providence, Rhode Island, United States, 02906

Contact: Linda Carpenter, MD 401-455-6632 linda_carpenter_md@brown.edu

Sub-Investigator: Eric Tirrell, BS

Sponsors and Collaborators

Brigham and Women's Hospital

Butler Hospital

More Information

• Responsible Party: Michael D. Fox, M.D.,Ph.D., Associate Professor, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT03276793
• Other Study ID Numbers: 2021P000335
• First Posted: September 8, 2017
• Last Update Posted: May 18, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Depression; Depressive Disorder; Behavioral Symptoms; Mood Disorders; Mental Disorders