Individualized (fMRI-guided) TMS Treatment for Depression

NCT06266390 | Active Not Recruiting DMC FDA Device

• 2 other identifiers: 8550071R61MH135428
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate the responses of the brain region known as the subgenual anterior cingulate cortex (sgACC) during transcranial magnetic stimulation (TMS) in individuals with depression. Specifically, investigators aim to determine whether the sgACC is engaged when TMS is delivered to specific targets and if the engagement of sgACC changes throughout a full TMS treatment intervention. To achieve this goal, the investigators will employ a combination of TMS and Magnetic Resonance Imaging (MRI) procedures. Study participation will include completing various questionnaires, clinical assessments, receiving a full transcranial magnetic stimulation (TMS) treatment intervention (every weekday for 6 weeks), and undergoing MRI scans, both with and without concurrent TMS.

Conditions

Depression; Major Depressive Disorder; Persistent Depressive Disorder

Keywords

Transcranial Magnetic Stimulation; Brain Imaging; Brain Stimulation; Depression; TMS; fMRI; non-invasive brain stimulation; TMS treatment; TMS for depression; individualized treatment

Outcome Measures

Primary Outcomes (1)

• sgACC Blood Oxygen Level Dependent (BOLD) signal change following single-pulse fMRI-guided TMS (TMS On vs TMS Off)

  This primary endpoint aims to directly assess sgACC engagement during fMRI-guided TMS by comparing sgACC BOLD signal under TMS On and TMS Off conditions. This sgACC BOLD signal change will be defined as sgACC evoked response henceforth.

  Single visit (~2 hours)

Secondary Outcomes (1)

• Change in sgACC evoked response Pre/Post TMS treatment with positive and negative sgACC correlated targets

  Up to 7 weeks

Study Arms (2)

Positive Correlation Target

ACTIVE COMPARATOR

TMS treatment will be administered using a TMS target positively correlated with the sgACC.

Device: Transcranial Magnetic Stimulation (TMS)

Anticorrelation Target

ACTIVE COMPARATOR

TMS treatment will be administered using a TMS target anticorrelated with the sgACC.

Device: Transcranial Magnetic Stimulation (TMS)

Interventions

Transcranial Magnetic Stimulation (TMS) DEVICE

The TMS intervention will involve two sets of Intermittent Theta-Burst Stimulation (iTBS) delivered every weekday for 4-6 weeks. Each iTBS set consists of 40 trains and a total of 1200 pulses, delivered approximately 15 minutes apart, resulting in 2400 pulses per session.

Anticorrelation Target; Positive Correlation Target

Eligibility Criteria

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

You may qualify if:

• years old
• DSM-5 diagnosis of major depressive (at least 90%) or persistent depressive disorder (no more than 10%) as per SCID clinical interview.
• Patient Health Questionnaire-9 (PHQ-9) score = or \> than 10
• Comprehension of instructions in the English language.
• Capacity to provide informed consent and follow study procedures.
• Availability for the duration of the study.

You may not qualify if:

• Implanted medical devices, metallic implants, or drug infusion pumps that are not MRI-safe (e.g., aneurysm clips, defibrillators, or cochlear implants)
• History of significant medical events (e.g., stroke, seizures, brain scarring) or neurological/neurodevelopmental conditions (e.g., epilepsy) that are contraindications for TMS and MRI or may adversely affect brain function and data interpretation.
• Current psychosis, mania, or substance use disorder
• Prior failed response to full rTMS or ECT/MST trial. Any successful prior treatments are acceptable and support a prognosis that a new rTMS treatment would be worth attempting.
• Inability to complete an MRI scan (e.g., claustrophobia, inability to remain still for extended periods).
• Inability to tolerate TMS administration
• Significant handicaps that would interfere with testing procedures
• Acute systemic infection, high fever
• Acute sleep deprivation or medication/substance intoxication or withdrawal (TMS seizure risk)
• Current use of cyclosporine, tacrolimus, or others that can cause leukoencephalopathy.
• Pregnancy
• Dialysis
• Suicide attempt in past 6 months (safety precaution)
• Transportation limits or physical limits to attending daily M-F treatment sessions.
• Per study physician discretion medications likely to interfere with blood flow or otherwise compromise functional imaging measures.

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Institutes of Health (NIH): collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Depression; Depressive Disorder, Major

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participants will not be informed on which target they have been assigned to.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Psychiatry

Model Details: Participants will receive rTMS to one of two targets. Participants will be randomly assigned to receive the TMS treatment intervention in one of two target conditions: half to their positive sgACC correlation target, while the remaining half to their negative sgACC correlation target.

Study Record Dates

• First Submitted: January 8, 2024
• First Posted: February 20, 2024
• Study Start: May 29, 2024
• Primary Completion: April 30, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: February 20, 2026

Record last verified: 2026-02

Locations

US (1)