Recruiting

rTMS

Sponsor:

Indiana University

Code:

NCT06511544

Conditions

Depression, Treatment Resistant

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Not accepted

Interventions

Transcranial magnetic stimulation

Study Details

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

Study ID

NCT06511544

Start date

Jan 2, 2024

Status verified date

Sep, 2025

Completion date

Jun 30, 2026

Anticipated

Primary completion date

Jun 30, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

20 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Active TMS

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

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.

Primary outcome measure

  • Functional Connectivity [ Time Frame: Before Transcranial magnetic stimulation (TMS) - immediately following TMS ]
  • Rumination [ Time Frame: Before TMS- immediately following TMS ]

Central Contacts and Locations

Central contacts

Susan K Conroy, MD PhD

317-963-7300sconroy@iu.edu

Locations

Goodman Hall Neuroscience Center

Recruiting

Indianapolis, Indiana, United States, 46202

Contacts

Susan K Conroy, MD PhD

317-963-7300sconroy@iu.edu

More Information

Sponsor

Indiana University

Last update posted

Sep 29, 2025

Last verified

Sep, 2025

Keywords

  • transcranial magnetic stimulation
  • functional magnetic resonance imaging

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Indiana University on 2025-09-29.