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

Suicidal Ideation Clinical Trial

— COMBAT-SI  

Official title:

Bilateral Accelerated Theta Burst Stimulation (aTBS) for Suicidal Ideation in Treatment-Resistant Depression

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05377177
• Other study ID #: 801566
• Status: Recruiting
• Phase: N/A
• Start date: September 2, 2022
• Est. completion date: July 2025

Study information

• Verified date: February 2024
• Source: University of California, San Diego
• Contact: Interventional Psychiatry
• Phone: (858) 207-0938
• Email: iptrials[@]health.ucsd.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 76
• Est. completion date: July 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Treatment-Resistant
• Suicidal Ideation
• Treatment-resistant Depression

Intervention

Device:
• Accelerated Theta Burst Stimulation
B65 magnetic coil stimulation applied to the dorsal lateral prefrontal cortex.

Locations

Country	Name	City	State
United States	UCSD Interventional Psychiatry	San Diego	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Diego	Brain & Behavior Research Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	6-months
Secondary	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.	6-months