Brain Connectivity in Depression

• ClinicalTrials.gov Identifier: NCT03276793
• Recruitment Status: Recruiting
• First Posted: September 8, 2017
• Last Update Posted: October 22, 2019
• Sponsor: Beth Israel Deaconess Medical Center
• Information provided by (Responsible Party): Michael Fox, Beth Israel Deaconess Medical Center

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, 80 subjects will be recruited. Subjects will be recruited from the Clinical Program of FDA approved TMS at the Berenson-Allen Center and the Butler TMS Clinic (40 per site). 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 Hamilton Depression Rating Scale (HDRS) 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

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• 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 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 Berenson-Allen Center for Non-invasive Brain Stimulation at Beth Israel Deaconess Medical Center, 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 (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: Molly Schineller, BS; 617-667-1571; mschinel@bidmc.harvard.edu

Locations

United States, Massachusetts

Beth Israel Deaconess Medical Center; Recruiting

Boston, Massachusetts, United States, 02215

Contact: Michael Fox, MD, PhD 617-667-0220 mfox3@bidmc.harvard.edu

Principal Investigator: Michael Fox, MD, PhD

Sub-Investigator: Daniel Press, MD

Sub-Investigator: Adam Stern, MD

Sub-Investigator: Ann Connor, RN

Sub-Investigator: Carrie Hinchman, BS

Sub-Investigator: Joanna Macone, RN

Sub-Investigator: Molly Schineller, BS

Sub-Investigator: Tina Arani, BS

Sub-Investigator: Shan Siddiqi, MD

Sub-Investigator: Joseph Taylor, MD, PhD

Sub-Investigator: Shobhik Chakraborty, BS

Sub-Investigator: Christopher Lin, BS

United States, Rhode Island

Butler Hospital; Not yet recruiting

Providence, Rhode Island, United States, 02906

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

Sub-Investigator: Eric Tirrell, BS

Sub-Investigator: Gina Sensale, BS

Sponsors and Collaborators

Beth Israel Deaconess Medical Center

More Information

• Responsible Party: Michael Fox, Assistant Professor of Neurology, Beth Israel Deaconess Medical Center
• ClinicalTrials.gov Identifier: NCT03276793 History of Changes
• Other Study ID Numbers: 2017P000514
• First Posted: September 8, 2017
• Last Update Posted: October 22, 2019
• Last Verified: October 2019

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