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

NCT06511544 | Recruiting DMC FDA Device

• 2 other identifiers: 13322K12TR004415
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Conditions

Depression, Treatment Resistant

Keywords

transcranial magnetic stimulation; functional magnetic resonance imaging

Outcome Measures

Primary Outcomes (2)

• Functional Connectivity

  Within-network functional connectivity of the default mode network during negative processing

  Before Transcranial magnetic stimulation (TMS) - immediately following TMS

• Rumination

  Scores on the Ruminative Response Scale (Range 22-88, with higher worse)

  Before TMS- immediately following TMS

Secondary Outcomes (1)

• Overall Depression Scores

  Before TMS- immediately following TMS

Study Arms (1)

Active TMS

EXPERIMENTAL

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

Device: Transcranial magnetic stimulation

Interventions

Transcranial magnetic stimulation 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.

Active TMS

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Indiana University: lead
• National Center for Advancing Translational Sciences (NCATS): collaborator

Study Sites (1)

Goodman Hall Neuroscience Center

Indianapolis, Indiana, 46202, United States

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Susan K Conroy, MD PhD

  Indiana University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Susan K Conroy, MD PhD

CONTACT

317-963-7300; sconroy@iu.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: July 8, 2024
• First Posted: July 22, 2024
• Study Start: January 2, 2024
• Primary Completion: June 30, 2026
• Study Completion: June 30, 2026
• Last Updated: September 29, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)