Cortical Inhibition as a Biomarker of Response in a Comparison of Bilateral Versus Unilateral Accelerated Theta Burst Stimulation for Suicidal Ideation in Treatment-Resistant Depression -COMBAT-SI

NCT05377177 | Recruiting DMC FDA Device

• 1 other identifier: 801566
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective clinical trial to confirm the effectiveness of bilateral accelerated theta burst stimulation (aTBS) on suicidal ideation (SI), while exploring cortical inhibition measures in this treatment paradigm. In this proposed study, the investigators will evaluate the anti-suicidal effects of bilateral aTBS over the DLPFC compared to accelerated intermittent theta burst stimulation (aiTBS) over the left DLPFC in participants with TRD and SI. Additionally, the investigators aim to identify neurophysiological targets through which bilateral aTBS induces remission of SI in TRD differentially from aiTBS.

Conditions

Suicidal Ideation; Treatment-resistant Depression

Keywords

theta burst stimulation; accelerated TBS; bilateral TBS

Outcome Measures

Primary Outcomes (1)

• Changes in scores on the suicide scale index (SSI) from baseline

  The primary outcome will be a comparison of change in score on the suicidality scale index (SSI) from baseline to endpoint of treatment between accelerated bilateral and unilateral treatment. The SSI contains 19 items scored from 0 to 2, higher scores indicating more severity, with overall scores ranging from 0 to 38The primary endpoint will be at treatment completion for both arms. The investigators will follow patients at 1, 2, 3, and 4 weeks post-treatment, as well as 3 and 6 months after treatment completion.

  6-months

Secondary Outcomes (2)

• Neurophysiological measures of cortical inhibition, N100, short interval cortical inhibition, and cortical evoked activity

  6-months

• Categorical suicidal clinical outcomes

  6-months

Study Arms (2)

Bilateral aTBS

EXPERIMENTAL

Patients will receive Bilateral accelerated theta-burst stimulation bilaterally for 5 consecutive days, with a total of 10 hours a day. treatment will be 10min with 50min of breaks in between the 10 sessions.

Device: Accelerated Theta Burst Stimulation

Unilateral aiTBS

ACTIVE COMPARATOR

Patients will receive unilateral accelerated theta-burst stimulation to the left side for 5 consecutive days, with a total of 10 hours a day. treatment will be 10min with 50min of breaks in between the 10 sessions. There will be a right DLPFC sham component to this treatment arm for all treatment sessions.

Device: Accelerated Theta Burst Stimulation

Interventions

Accelerated Theta Burst Stimulation DEVICE

B65 magnetic coil stimulation applied to the dorsal lateral prefrontal cortex.

Bilateral aTBS; Unilateral aiTBS

Eligibility Criteria

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

You may qualify if:

• years old.
• Diagnosis of major depressive episode, confirmed on Mini-International Neuropsychiatric Interview (MINI), with HRSD score ≥18.
• Ongoing SI present beyond screening phase of study (confirmed with Beck SSI score ≥4).
• Pass the TMS adult safety screening (TASS) questionnaire and the MRI safety screening questionnaire.
• Have failed to achieve a clinical response to an adequate dose of two antidepressants based on an Antidepressant Treatment History Form (ATHF) score for each antidepressant trial of \> 3 in the current episode OR have been unable to tolerate at least 2 separate trials of antidepressants of inadequate dose and duration (ATHF score of 1 or 2 on those 2 separate antidepressants) OR have a combination of one failed trial and one not tolerated trial, per the definitions above.
• Psychiatric illness due to a general medical condition (GMC) has been ruled out during initial assessment.
• Voluntary outpatients capable to consent to treatment and seen at the UC San Diego Health Interventional Psychiatry program.
• Able to adhere to the treatment schedule.

You may not qualify if:

• Have a confirmed diagnosis of substance use disorder within the last 3 months.
• Have a lifetime diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms.
• Have a diagnosis of obsessive compulsive disorder, post-traumatic stress disorder (current or within the last year), anxiety disorder (generalized anxiety disorder, social anxiety disorder, panic disorder), or dysthymia, that is assessed by a study investigator to be primary and causing greater impairment than MDD.
• Have a diagnosis of any personality disorder, and assessed by a study investigator to be primary and causing greater impairment than MDD.
• Currently pregnant or lactating, or woman or childbearing age without adequate birth control.
• Non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview).
• Not capable to consent to treatment and/or not suitable for outpatient treatment.
• Have a concomitant major unstable medical illness, cardiac pacemaker or implanted medication pump; Have any significant neurological disorder or insult including, but not limited to: any condition likely to be associated with increased intracranial pressure, space occupying brain lesion, any history of seizure except those therapeutically induced by ECT or a febrile seizure of infancy, cerebral aneurysm, Parkinson's disease, Huntington's chorea, multiple sclerosis, significant head trauma with loss of consciousness for greater than 5 minutes; Have an intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed.
• Currently take more than lorazepam 2 mg daily (or equivalent) or any dose of an anticonvulsant due to the potential to limit rTMS efficacy.

Sponsors & Collaborators

• University of California, San Diego: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

UCSD Interventional Psychiatry

San Diego, California, 92127, United States

RECRUITING

MeSH Terms

Conditions

Suicidal Ideation; Depressive Disorder, Treatment-Resistant

Condition Hierarchy (Ancestors)

Suicide; Self-Injurious Behavior; Behavioral Symptoms; Behavior; Depressive Disorder; Mood Disorders; Mental Disorders

Central Study Contacts

Interventional Psychiatry

CONTACT

(858) 657-6152; iptrials@health.ucsd.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: A sham component will be used over the right DLPFC for unilateral aiTBS treatment. This treatment component will mitigate concerns of expectancy, and will lead to blinding for patients. The Cool B65 A/P coil is unmarked, with one side producing active treatment and the other sham treatment with concurrent electrical stimulation, which accurately mimics active stimulation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director of Interventional Psychiatry; Assistant Clinical Professor of Psychiatry

Model Details: Patients enrolled in the study will be randomized to bilateral vs. unilateral aiTBS in a 1:1 ratio . Treatments will be over 1 week.

Study Record Dates

• First Submitted: March 24, 2022
• First Posted: May 17, 2022
• Study Start: September 2, 2022
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): July 30, 2030
• Last Updated: November 5, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)