Suicidal IdeationCOMBAT-SINCT05377177
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
A study testing Accelerated Theta Burst Stimulation in people with Suicidal Ideation and Treatment-resistant Depression, run by University of California, San Diego at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Suicidal Ideation, Treatment-resistant Depression
- What is being tested?
- Accelerated Theta Burst Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 76 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Sep 2022to 30 Jul 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18-70 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.
Who cannot join
- 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.
- 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).
- Currently pregnant or lactating, or woman or childbearing age without adequate birth control.
Show all 10Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
UCSD Interventional Psychiatry
San Diego, California, 92127
Interventional Psychiatry, (858) 207-0938, iptrials@health.ucsd.edu
About this study
Official title: 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)
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.
Read the 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
- Being tested
- Accelerated Theta Burst Stimulation
- Keywords
- theta burst stimulation, accelerated TBS, bilateral TBS
- Medical subject headings
- Suicidal Ideation, Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Accelerated Theta Burst StimulationDevice
B65 magnetic coil stimulation applied to the dorsal lateral prefrontal cortex.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Device: Accelerated Theta Burst Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6-months
Secondary outcomes (2)
Neurophysiological measures of cortical inhibition, N100, short interval cortical inhibition, and cortical evoked activity
Analysis of transcranial magnetic stimulation concurrent with electroencephalogram (TMS-EEG) to extract effective connectivity metrics between the subgenual cingulate (SGC) and the dorsolateral prefrontal cortex (DLPFC) as suicidality biomarkers, as measured by changes in scores on the SSI, for left aiTBS compared to bilateral aTBS.
Measured: 6-months
Categorical suicidal clinical outcomes
Suicide attempts and completions will be recorded as adverse events throughout the duration of the study. The investigators will complete categorical sensitivity analyses for these outcomes between treatment groups.
Measured: 6-months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2022
- Study start2 Sep 2022
- Primary completion1 Aug 2029 (estimated)
- Study completion30 Jul 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Suicidal IdeationStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients enrolled in the study will be randomized to bilateral vs. unilateral aiTBS in a 1:1 ratio . Treatments will be over 1 week.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 76 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Principal investigator, Cory Weissman, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05377177
- Sponsor's protocol ID
- 801566
- Acronym
- COMBAT-SI
- Status last verified
- Nov 2025
- First submitted
- 24 Mar 2022
- Last updated
- 5 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT05377177
- Acronym / sponsor ID
- COMBAT-SI / 801566
- Conditions
- Suicidal Ideation, Treatment-resistant Depression
- Keywords
- theta burst stimulation, accelerated TBS, bilateral TBS
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 76 participants (estimated)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- 2 Sep 2022 (actual)
- Primary completion
- 1 Aug 2029 (estimated)
- Study completion
- 30 Jul 2030 (estimated)
- First posted
- 17 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Patients enrolled in the study will be randomized to bilateral vs. unilateral aiTBS in a 1:1 ratio . Treatments will be over 1 week.
| Arm | Type | Receives |
|---|---|---|
| Bilateral aTBS | Experimental | Device: Accelerated Theta Burst StimulationPatients 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. |
| Unilateral aiTBS | Active comparator | Device: Accelerated Theta Burst StimulationPatients 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 18-70 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.
Key exclusion criteria (10 listed)
- 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.
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Accelerated Theta Burst StimulationB65 magnetic coil stimulation applied to the dorsal lateral prefrontal cortex. | Device | Bilateral aTBS, Unilateral aiTBS |
Primary outcome
Changes in scores on the suicide scale index (SSI) from baseline
Time frame: 6-months
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.
2 secondary outcomes
Neurophysiological measures of cortical inhibition, N100, short interval cortical inhibition, and cortical evoked activity
Time frame: 6-months
Categorical suicidal clinical outcomes
Time frame: 6-months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2025.
- Individual participant dataSharing planned: No
Related trials for Suicidal Ideation
Not yet recruiting
A Pre-post Study of a Lethal Means Safety Planning Intervention for Youth at Elevated Suicide Risk in the Emergency Department
Suicidal Ideas, Suicidal Ideation
RecruitingObservational study
Student Precarity and Psychiatry
Depressive Disorder, Major, Generalized Anxiety Disorder
Not yet recruiting
SERENE Low-Intensity Focused Ultrasound for Cognitive Control
Suicidal Ideation, Cognitive Control
Not yet recruiting
A MRT to Optimize a JITAI for Alcohol Craving and Suicide Ideation
Alcohol Use Disorder (AUD), Suicide Ideation
Enrolling by invitation
Pilot Study of a Modified Safety Planning Intervention for Elementary School-Aged Children - Main Study
Suicidal Ideation, Suicidal Behaviors
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Accelerated Theta Burst Stimulation in people with Suicidal Ideation and Treatment-resistant Depression, run by University of California, San Diego at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Interventional Psychiatry ((858) 657-6152, iptrials@health.ucsd.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in scores on the suicide scale index (SSI) from baseline (time frame: 6-months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2025.