Neuronavigated aiTBS for TRD

NCT07329153 | Not Yet Recruiting FDA Device

• 1 other identifier: STU-2025-1926
• Study Type: interventional
• Target: 247
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to confirm the efficacy of two recently introduced repetitive transcranial magnetic stimulation (rTMS) interventions - accelerated intermittent theta-burst stimulation (aiTBS) and individualized neuronavigation - in treatment-resistant depression (TRD). Using a three-arm design (neuronavigated aiTBS, non-neuronavigated aiTBS, and sham), this randomized controlled trial (RCT) is the first to specifically investigate the incremental benefit of neuronavigation within an accelerated stimulation protocol, as well as the first confirmatory RCT comparing the efficacy of each of these active treatments vs. sham, overcoming previous generalizability issues and being conducted in an independent, multicenter US TRD sample.

Conditions

Treatment Resistant Depression (TRD)

Keywords

depression; TMS

Outcome Measures

Primary Outcomes (1)

• HDRS-17 - Depression severity assessment

  depression severity as assessed by the Hamilton Depression Rating Scale-17 items (HDRS-17)

  From Baseline visit until week 5 visit

Secondary Outcomes (2)

• Montgomery-Åsberg Depression Rating Scale (MADRS)

  From Baseline visit until week 5 visit.

• Quick Inventory of Depressive Symptoms-Self Report (QIDS-SR)

  From Baseline visit until week 5 visit

Study Arms (3)

Neuronavigated aiTBS

EXPERIMENTAL

TBS device placement during treatment determined by MRI imaging

Device: aiTBS

Non-Neuronavigated aiTBS

ACTIVE COMPARATOR

Conventional device placement during treatment

Device: aiTBS

Sham aiTBS

SHAM COMPARATOR

identical procedures as the other 2 groups but without turning on the device

Device: aiTBS

Interventions

aiTBS DEVICE

Repetitive transcranial magnetic stimulation (rTMS) interventions - accelerated intermittent theta-burst stimulation (aiTBS) and individualized neuronavigation.

Neuronavigated aiTBS; Non-Neuronavigated aiTBS; Sham aiTBS

Eligibility Criteria

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

You may qualify if:

• Age: 18 to 65 years at the time of consent
• Diagnosis: Current major depressive episode (MDE) in the context of unipolar major depressive disorder (MDD), as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), confirmed by clinical psychiatric interview
• Treatment Resistance: Documented failure to respond to at least two adequate antidepressant trials on the Antidepressant Treatment History Form-Short Form (ATHF-SF). An adequate trial is defined as:
• Antidepressant medication at the maximum tolerated dose for at least 6 weeks, OR
• Evidence-based psychotherapy consisting of at least 12 sessions
• Depression Severity: Montgomery-Åsberg Depression Rating Scale (MADRS) score \>19 at screening, indicating moderate to severe depression
• Medication Stability: No changes in antidepressant medication type or dose for at least 6 weeks prior to randomization. Stable doses of permitted medications must be maintained throughout the trial
• Informed Consent: Demonstrated capacity to provide written informed consent and comply with study procedures
• Availability: Ability to attend treatment sessions for 15 consecutive workdays (approximately 90 minutes per day) and complete assessments including 4-hour evaluations at baseline and endpoint

You may not qualify if:

• Any psychiatric disorder other than MDD and comorbid anxiety disorders, including but not limited to:
• (i) Bipolar disorder (Type I or II) (ii) Schizophrenia spectrum or other psychotic disorders (iii) Post-traumatic stress disorder (PTSD) (iv) Attention-deficit/hyperactivity disorder (ADHD) (v) Autism spectrum disorder (ASD) (vi) Obsessive-compulsive disorder (OCD) (vii) Current DSM-5 substance-use disorder (abuse or dependence) within the past 6 months, except nicotine dependence
• Personality disorder confirmed on clinical interview by an experienced study psychiatrist
• Severe suicidal ideation with structured plan (HDRS-17 item 3 score \>2) or as determined by the evaluating psychiatrist
• Depressive symptoms better explained by another psychiatric condition, a medical condition, substance use, or use of medications
• Any neurological disorder including but not limited to:
• (i) History of seizure disorder or epilepsy (ii) Family history of epilepsy (first-degree relatives) (iii) Significant head trauma with loss of consciousness \>5 minutes (iv) Stroke or transient ischemic attack (v) Neurodegenerative disorders (e.g., Parkinson's disease, multiple sclerosis, dementia) (vi) Brain tumor or intracranial mass lesion
• Unstable medical condition, defined as any condition requiring acute medical intervention or hospitalization within the past 3 months, or any condition that in the investigator's judgment could affect participant safety or study outcomes
• Contraindications to TMS/MRI:
• Presence of ferromagnetic material in or near the head, including:
• (i) Intracranial implants (e.g., aneurysm clips, shunts, stimulators) (ii) Cochlear implants or hearing aids (iii) Metallic facial tattoos or permanent makeup (iv) Other implanted medical devices deemed unsafe for MRI/TMS
• Inability to tolerate MRI scanning due to claustrophobia or other reasons
• Current use of medications known to significantly alter cortical excitability:
• Anticonvulsants (including those used for mood stabilization)
• Psychostimulants

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• University of California, San Diego: collaborator
• Cornell University: collaborator

Study Sites (3)

University of California at San Diego (UCSD)

San Diego, California, 92127, United States

Location

Cornell University

New York, New York, 10065, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Depression

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Chief of the Division of Interventional Psychiatry

Study Record Dates

• First Submitted: January 7, 2026
• First Posted: January 9, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): June 1, 2031
• Study Completion (Estimated): September 1, 2031
• Last Updated: January 9, 2026

Record last verified: 2026-01

Locations

US (3)