Rapid Acting TMS for Suicide Ideation in Depression

Sponsor

Stanford University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05100004

Collaborator

(none)

100

Enrollment

Location

Arms

45.8

Anticipated Duration (Months)

2.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study evaluates the effects of an accelerated schedule of theta-burst stimulation, termed accelerated intermittent theta-burst stimulation (aiTBS), on the neural networks underlying explicit and implicit suicidal cognition in inpatients with major depressive disorder.

Condition or Disease	Intervention/Treatment	Phase
Depressive Disorder, Major Suicide	Device: Accelerated Theta Burst Stimulation Device: Sham Stimulation	N/A

Detailed Description

Investigators recently developed a form of neuromodulation termed Stanford Neuromodulation Therapy (SNT). SNT-induced remission is associated with significant reductions in the functional connectivity of the neural network underlying explicit suicidal cognition (between sgACC-DMN). This project aims to further elucidate the SNT induced neural network changes underlying explicit suicidal cognition.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Patients will receive either active or sham stimulation to the DLPFC. Patients will be randomized to either condition with a 50:50 chance.Patients will receive either active or sham stimulation to the DLPFC. Patients will be randomized to either condition with a 50:50 chance.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Rapid Acting Transcranial Magnetic Stimulation for Suicide Ideation in Depression

Actual Study Start Date :

Nov 7, 2021

Anticipated Primary Completion Date :

Sep 1, 2025

Anticipated Study Completion Date :

Sep 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Left Dorsolateral Prefrontal Cortex (L-DLPFC) The accelerated theta burst stimulation protocol will be applied to the left dorsolateral prefrontal cortex (DLPFC)	Device: Accelerated Theta Burst Stimulation Participants who are randomly assigned to this group will receive active iTBS (intermittent theta burst stimulation) to the left DLPFC. Stimulation intensity will be standardized at 90% of resting motor threshold (adjusted for cortical depth). Stimulation will be delivered using the Magventure Magpro X100 TMS system.
Sham Comparator: Sham Stimulation Sham (non-active) stimulation will be applied to the left dorsolateral prefrontal cortex (DLPFC) region	Device: Sham Stimulation Participants who are randomly assigned to this group will receive sham stimulation to the left DLPFC. Sham stimulation will be delivered using the Magventure Magpro X100 TMS system.

Arm

Intervention/Treatment

Active Comparator: Left Dorsolateral Prefrontal Cortex (L-DLPFC)

The accelerated theta burst stimulation protocol will be applied to the left dorsolateral prefrontal cortex (DLPFC)

Device: Accelerated Theta Burst Stimulation

Participants who are randomly assigned to this group will receive active iTBS (intermittent theta burst stimulation) to the left DLPFC. Stimulation intensity will be standardized at 90% of resting motor threshold (adjusted for cortical depth). Stimulation will be delivered using the Magventure Magpro X100 TMS system.

Sham Comparator: Sham Stimulation

Sham (non-active) stimulation will be applied to the left dorsolateral prefrontal cortex (DLPFC) region

Device: Sham Stimulation

Participants who are randomly assigned to this group will receive sham stimulation to the left DLPFC. Sham stimulation will be delivered using the Magventure Magpro X100 TMS system.

Outcome Measures

Primary Outcome Measures

Change in suicidal ideation as measured by the modified Scale for Suicide Ideation (m-SSI). [At baseline (day 0) and at post-inpatient treatment completion (day 2-7)]
The modified Scale for Suicide (m-SSI) is an 18-item clinician rated scale that measures suicidal ideation. Each item is scored from 0-3. Scores are summed for 1 total score. Higher scores indicate more severe suicidal ideation. Investigators will assess change in m-SSI scores at the post-inpatient treatment completion (day 2-7).

Secondary Outcome Measures

Rates of remission immediately after treatment in the Montgomery-Åsberg Depression Rating Scale (MADRS) score. [At baseline (day 0) and at post-inpatient treatment completion (day 2-7)]
The Montgomery-Åsberg Depression Rating Scale (MADRS), is a ten item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. Remission is defined as MADRS ≤10.
Rates of response immediately after treatment in the Montgomery-Åsberg Depression Rating Scale (MADRS) score. [At baseline (day 0) and at post-inpatient treatment completion (day 2-7)]
The Montgomery-Åsberg Depression Rating Scale (MADRS), is a ten item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. Response is defined as a reduction of >/=50% of MADRS baseline score.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 22-65 year old at the time of screening on voluntary or involuntary hold
Able to read, understand, and provide written, dated informed consent prior to screening. Participants will be deemed likely to comply with study protocol and communicate with study personnel about adverse events and other clinically important information.
Diagnosed with Major Depressive Disorder (MDD) or Bipolar Affective Disorder II (BAPD II), according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5).

Endorse suicidal ideation (score ≥9 on the SSI-M).

Meet the threshold on the MADRS and HAMD-17 with a total score of >/=20 at baseline.
Not in a current state of mania (Young Mania Rating Scale) or psychosis (MINI)
Have to be TMS naive
In good general health, as ascertained by medical history.
Scheduled with a psychiatrist
Access to clinical rTMS after hospital discharge
If participant is of childbearing potential and not already pregnant, must agree to use adequate contraception prior to study and for the duration of study participation.
No recent use (for the actual depressive episode) of rapid acting antidepressive agent (ketamine)

Exclusion Criteria:

Any abnormalities indicated on previous MRI scans e.g. structural neurological condition, more subcortical lesions than would be expected for age, stroke affecting stimulated area or connected areas or any other clinically significant abnormality that might affect safety, study participation, or confound interpretation of study results.
Metal implant in brain (e.g. deep brain stimulation), cardiac pacemaker, or cochlear
History of epilepsy/ seizures (including history of withdrawal/ provoked seizures)
Shrapnel or any ferromagnetic item in the head.
Pregnancy: The effects of rTMS on the developing human fetus are incipient and still uncertain (25). Pregnant women will not be enrolled into this study. Women of childbearing potential must agree to use adequate contraception (hormonal / barrier method of birth control or abstinence) prior to study entry and for the duration of study participation. Females of childbearing-age, will have a pregnancy test prior to receiving each rTMS stimulation session. Should a woman become pregnant or suspects she is pregnant while participating in this study, she should inform study staff.
Autism Spectrum disorder
A diagnosis of obsessive-compulsive disorder (OCD)
The presence or diagnosis of prominent anxiety disorder, personality disorder, or dysthymia
Any current or past history of any physical condition which in the investigator's opinion might put the subject at risk or interfere with study results interpretation.
Active substance use (<1 week) or intoxication verified by toxicology screen--of cocaine, amphetamines, benzodiazepines
Cognitive impairment (including dementia)
Current severe insomnia (must sleep a minimum of 5 hours the night before stimulation)
Current mania or psychosis
Bipolar Affective Disorder I and primary psychotic disorders.
Showing symptoms of withdrawal from alcohol or benzodiazepines
IQ<70
Parkinsonism or other movement d/o determined by PI to interfere with treatment
Desirous of getting ECT and previous intolerant exposure to ECT
Any other indication the PI feels would comprise data
No access to clinical rTMS after discharge.
Previous TMS exposure.
Depth-adjusted aiTBS treatment dose > 65% maximum stimulator output (MSO).