rTMS to Target Neural Connectivity and Rumination in Treatment-Resistant Depression

NCT ID: NCT06511544

Last Updated: 2025-09-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-02
• Study Completion Date: 2026-06-30

Brief Summary

The goal of this clinical trial is to learn if Transcranial Magnetic Stimulation (TMS) to part of the brain called the ventromedial prefrontal cortex (VMPFC) can treat a symptom called rumination in adults with major depression that has not responded to at least one medication trial. The main question it aims to answer are:

Does TMS to the VMPFC change brain activity on functional magnetic resonance imaging (fMRI) during a negative self-referential processing task in adults with depression? Does TMS to the VMPFC affect rumination in adults with depression? Researchers will compare brain scans and rumination scores before, during, and immediately after TMS.

Participants will:

Undergo three functional MRI scans Undergo a course of 20 TMS treatments Respond to clinical questionnaires and complete a computer behavioral task

Detailed Description

This will be a single-site, pilot, open-label, within-subject design study. 20 participants with treatment-resistant depression, defined as a failure to respond to at least one antidepressant medication trial within a current major depressive episode, will be recruited. Prior to intervention, participants will undergo self-report and clinician-administered assessments (in-person or virtual with both audio and video on using secure health telecommunication method), as well as a fMRI during resting state and a self-referential processing task. The baseline scan will also include a high-resolution structural sequence for neuronavigational purposes. Then, participants will receive 20 daily (5 days/week) sessions of rTMS to the VMPFC along with weekly assessments. Participants will undergo a repeated fMRI scan early in the course of treatment (after session 5) when we would expect neural changes to be evident but prior to any robust overall antidepressant effect, as well as at the end of the rTMS course (after session 20). Scores on the depression and rumination scales will be recorded prior to intervention and weekly thereafter. Contact with subjects will be conducted once via telephone at two weeks after the end of study intervention as an adverse event assessment. In the event that new or persistent adverse events felt to be related to the study intervention occur following the termination of study procedures, subjects may be brought in for further safety assessments.

Conditions

Depression, Treatment Resistant

Study Design

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

Study Groups

Active TMS

All participants will receive active TMS to the VMPFC for 20 sessions

Group Type: EXPERIMENTAL

Transcranial magnetic stimulation

Intervention Type: DEVICE

rTMS delivered at 1 Hz for 1800 pulses over 30 minutes for 20 daily sessions, 5 days/week. Treatment will be directed to the ventromedial prefrontal cortex using each participant's structural MRI.

Interventions

Transcranial magnetic stimulation

rTMS delivered at 1 Hz for 1800 pulses over 30 minutes for 20 daily sessions, 5 days/week. Treatment will be directed to the ventromedial prefrontal cortex using each participant's structural MRI.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Diagnosis of unipolar major depressive disorder without psychotic features by the Mini-International Neuropsychiatric Interview (MINI) and confirmed by study psychiatrist
• First depressive episode prior to age 50
• Current moderate to severe depression, Hamilton Depression Rating Scale (HDRS) ≥17)
• Failure to respond to ≥1 antidepressant medication at adequate dose and duration in the current depressive episode; (note: this criterion is designed to be consistent with the original 2008 FDA-labeled indication for TMS in Major Depressive Disorder, that specifies failure to respond to "one prior medication at or above the minimal effective dose and duration in the current episode" (https://www.accessdata.fda.gov/cdrh_docs/pdf8/K083538.pdf). ))
• Off psychotropic medications OR on a stable dose of medication(s) for 6 weeks, and willing to remain on stable medication dosage throughout the study
• Capacity to consent
• Ability to safely receive MRI

Exclusion Criteria

• Actively/imminently suicidal, Quick Inventory of Depressive Symptomatology (QIDS) item 12 score >2)
• Current depressive episode duration > 5 years
• Presence of clinically significant psychiatric diagnoses other than unipolar, non-psychotic major depression, such as post-traumatic stress disorder (PTSD) or obsessive-compulsive disorder (OCD)
• Evidence of cognitive impairment, Montreal Cognitive Assessment (MOCA) < 23)
• Significant substance use disorder within past 6 months
• New-onset psychotherapy and/or somatic therapy (e.g., light therapy) within 6 weeks of screening
• Prior exposure to any form of TMS
• Have participated in any clinical trial with an investigational drug or device within the past 6 weeks prior to screening
• Failure to respond to Electroconvulsive therapy (ECT)
• Any history of neurosurgery to treat a neurologic or psychiatric disorder (e.g. Vagus nerve stimulation, cortical stimulation, deep brain stimulation, or ablative surgery)
• Unstable medical illness
• Evidence or history of significant neurological disorder, including moderate-severe head trauma, stroke, Parkinson's disease or other movement disorder (except benign essential tremor)
• Epilepsy
• History of seizures (except juvenile febrile seizures or provoked seizures at the PI's discretion) or any condition/concurrent medication that could notably lower seizure threshold
• Pregnancy or planned pregnancy during the study
• Presence of cardiac pacemaker, cochlear implant, or other implanted electronic device
• Any vision problem that will prevent them from seeing the adjectives presented inside the MRI scanner without glasses

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Center for Advancing Translational Sciences (NCATS)

NIH

Sponsor Role: collaborator

Indiana University

OTHER

Sponsor Role: lead

Responsible Party

Susan K. Conroy

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Susan K Conroy, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Indiana University School of Medicine

Locations

Goodman Hall Neuroscience Center

Indianapolis, Indiana, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Susan K Conroy, MD PhD

Role: CONTACT

sconroy@iu.edu

317-963-7300

Facility Contacts

Susan K Conroy, MD PhD

Role: primary

sconroy@iu.edu

317-963-7300

Other Identifiers

K12TR004415

Identifier Type: NIH

Identifier Source: secondary_id

View Link

13322

Identifier Type: -

Identifier Source: org_study_id