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

NCT ID: NCT05377177

Last Updated: 2025-11-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 76 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-02
• Study Completion Date: 2030-07-30

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.

Detailed Description

Suicidality is a growing epidemic, as over 700,000 people die by suicide around the world annually. Current treatments for suicidality are limited and novel treatments for suicidality are desperately needed. There is early evidence to suggest that the non-invasive brain stimulation treatment called repetitive transcranial magnetic stimulation, or rTMS, is better than placebo at eliminating suicidal ideation (SI) in patients with hard to treat depressive illness (treatment-resistant depression; TRD). The UCSD Interventional Psychiatry lab was the first group to demonstrate that bilateral rTMS, targeted to specific areas of the frontal lobes of the brain, is more effective than placebo for SI. Recent evidence from the lab also showed that improvement in SI with brain stimulation treatment is correlated with changes in specific measures of neuronal communication, that is cortical inhibition, in these same brain regions. A prospective clinical trial to confirm the effectiveness of bilateral rTMS on SI, while exploring cortical inhibition measures in this treatment paradigm, is prudent and urgently needed. In this proposed study, the investigators plan to evaluate the anti-suicidal effects of bilateral aTBS over the DLPFC (an accelerated form of rTMS delivered with multiple theta burst treatments per day) compared to 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Bilateral aTBS

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.

Group Type: EXPERIMENTAL

Accelerated Theta Burst Stimulation

Intervention Type: DEVICE

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

Unilateral aiTBS

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.

Group Type: ACTIVE_COMPARATOR

Accelerated Theta Burst Stimulation

Intervention Type: DEVICE

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

Interventions

Accelerated Theta Burst Stimulation

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

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. 18-70 years old.

2. Diagnosis of major depressive episode, confirmed on Mini-International Neuropsychiatric Interview (MINI), with HRSD score ≥18.

3. Ongoing SI present beyond screening phase of study (confirmed with Beck SSI score ≥4).

4. Pass the TMS adult safety screening (TASS) questionnaire and the MRI safety screening questionnaire.

5. 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.

6. Psychiatric illness due to a general medical condition (GMC) has been ruled out during initial assessment.

7. Voluntary outpatients capable to consent to treatment and seen at the UC San Diego Health Interventional Psychiatry program.

8. Able to adhere to the treatment schedule.

Exclusion Criteria

1. Have a confirmed diagnosis of substance use disorder within the last 3 months.

2. Have a lifetime diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms.

3. 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.

4. Have a diagnosis of any personality disorder, and assessed by a study investigator to be primary and causing greater impairment than MDD.

5. Have SI prompting emergent involuntary hospital stay (SI in which the participant can maintain voluntary and capable outpatient status as well as recent suicide attempt will not be exclusionary).

6. Currently pregnant or lactating, or woman or childbearing age without adequate birth control.

7. Non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview).

8. Not capable to consent to treatment and/or not suitable for outpatient treatment.

9. 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.

10. Currently take more than lorazepam 2 mg daily (or equivalent) or any dose of an anticonvulsant due to the potential to limit rTMS efficacy.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

University of California, San Diego

OTHER

Sponsor Role: lead

Responsible Party

Cory Weissman

Medical Director of Interventional Psychiatry; Assistant Clinical Professor of Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

UCSD Interventional Psychiatry

San Diego, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Interventional Psychiatry

Role: CONTACT

iptrials@health.ucsd.edu

(858) 657-6152

Facility Contacts

Interventional Psychiatry

Role: primary

iptrials@health.ucsd.edu

(858) 207-0938

Provided Documents

Document Type: Study Protocol and Informed Consent Form

View Document

Other Identifiers

801566

Identifier Type: -

Identifier Source: org_study_id