TBS,TMS, Suicidal Ideation, Magnetic Resonance Imaging, Dorsolateral Prefrontal Cortex, Ventrolateral Prefrontal Cortex

Study Overview
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Brief Summary
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Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technique, its approved therapeutic indication is high-frequency stimulation to the left dorsolateral prefrontal cortex (DLPFC) for treatment resistant.

Detailed Description
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investigators design a prospective three-year study to exam the effect of TBS on reducing suicidality targeted at left DLPFC vs VLPFC, and guided by task fMRI neuronavigation and sham. Investigators will adopt personalized left DLPFC and VLPFC localization from baseline task fMRI data. Due to the global brain atrophic changes in the older adults, this issue has been even more important. Investigators will enroll 163 late life depression cases, they will be randomly allocated to either DLPFC group (65 cases), or VLPFC group (65 cases) and sham group (33 cases). To sum up, investigators seek to evaluate the impact of an acute course of TBS guided by tsked fMRI neuronavigation on suicidal ideation, and through follow-up for 6 months, investigators expect to examine (1) suicidal ideation, structural and functional brain differences, inflammatory markers pre/post TBS treatment, explore the link between the mechanism underlying of TBS on brain connectivity and therapeutic effects (2) Association of suicide ideation and neurocognitive function, inflammatory factors and brain imaging data. Exploratory analysis will assess suicide ideation as mediator in the association of neurocognitive deficit and functional connectivity or neurocognitive deficit as mediator in the association of suicide ideation and brain imaging data (3) The trajectories of suicidal ideation in late life depression, to analysis whether the association of cognitive dysfunction and suicidal ideation occurs across time and the prediction of neurocognitive function.(4) Explore the association of suicidal ideation the depression severity, to test if suicidal ideation could be an independent treatment target (5) Investigate the plausible predictors of neuropsychological profiles or neuroimaging findings associated to the effect of TBS in reducing suicidal ideation, which could provide a more efficient strategy for suicide prevention in the elder.

Official Title
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Theta Burst Stimulation, Transcranial Magnetic Stimulation, Late Life Depression, Suicidal Ideation, Functional Magnetic Resonance Imaging, Dorsolateral Prefrontal Cortex, Ventrolateral Prefrontal Cortex

Conditions
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Late Life Depression

Intervention / Treatment
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* Device: Transcranial magnetic stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 50 years. Major depressive disorder (MDD). Right handiness with a score ≥ 12 on the Beck Scale of Suicidal Ideation (BSSI) and a score of at least 3 on Question #3 (Suicide: 3 ideas and gestures of suicide) of the HAMD Exclusion Criteria: Inability to provide informed consent. Dementia, as defined by MoCA 23/24. Other major mental or current psychotic symptoms Active current suicidal intent as evidenced or the endorsement of an actual attempt, interrupted attempt, Have known preexisting noise-induced hearing loss, concurrent treatment with ototoxic medications, or with cochlear implants are on medications known to lower seizure threshold. Alcohol or other substances abuse of or dependence on within the past 3 months Organic brain, head trauma, Elevated risk of seizure due to TBI Participation in concurrent clinical trial Non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview). Unstable medical illness, including delirium, malignancy, uncontrolled diabetes mellitus, hypertension, hyperlipidemia, or cerebrovascular or cardiovascular risk factors that are not under medical management. Unstable cardiac disease or recent (<3m) myocardial infarction Mental implement in the brain, claustrophobia Ever received ECT, TMS Consent procedures.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dorsolateral prefrontal cortex<br>Age > 50 years. Major depressive disorder (MDD). Right handiness with a score ≥ 12 on the Beck Scale of Suicidal Ideation (BSSI) and a score of at least 3 on Question #3 (Suicide: 3 ideas and gestures of suicide) of the HAMD | Device: Transcranial magnetic stimulation<br>* Transcranial magnetic stimulation<br>|
| Experimental: ventrolateral prefrontal cortex<br>Age > 50 years. Major depressive disorder (MDD). Right handiness with a score ≥ 12 on the Beck Scale of Suicidal Ideation (BSSI) and a score of at least 3 on Question #3 (Suicide: 3 ideas and gestures of suicide) of the HAMD | Device: Transcranial magnetic stimulation<br>* Transcranial magnetic stimulation<br>|
| Placebo Comparator: sham comparator<br>Age > 50 years. Major depressive disorder (MDD). Right handiness with a score ≥ 12 on the Beck Scale of Suicidal Ideation (BSSI) and a score of at least 3 on Question #3 (Suicide: 3 ideas and gestures of suicide) of the HAMD | Device: Transcranial magnetic stimulation<br>* Transcranial magnetic stimulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Beck Scale for Suicide Ideation (BSSI) at baseline | the severity of suicide ideation(the score range from 0-38,the higher score indicates higher severity. | baseline(1 week before treatment) | 
| Beck Scale for Suicide Ideation (BSSI)at the 1st month | the severity of suicide ideation(the score range from 0-38,the higher score indicates higher severity) | the 1st month (4 weeks after baseline) | 
| Beck Scale for Suicide Ideation (BSSI)at the 3rd month | the severity of suicide ideation(the score range from 0-38,the higher score indicates higher severity) | the 3rd month(12 weeks after baseline) | 
| Beck Scale for Suicide Ideation (BSSI)at the 6th month | the severity of suicide ideation(the score range from 0-38,the higher score indicates higher severity) | the 6th month(24 weeks after baseline) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geriatric Depression Scale | the severity of depression(the score range from 0-15,the higher score means worse outcome) | baseline(1 week before treatment), the 1st month(4 weeks after baseline), the 3rd moth(12 weeks after baseline), and the 6th month(24 weeks after baseline) | 
| structural and functional connectivity | Brain MRI connectivity change | baseline(1 week before treatment), the 1st month(4 weeks after baseline) | 
| MRI T1 | Brain structural volumes (cm) | baseline(1 week before treatment), the 1st month(4 weeks after baseline) | 
| functional MRI (resting-state/biological motion task) - BOLD signal | Blood-oxygen-level-dependent (BOLD) signal is a measurement used in fMRI which reflects the neural activity. | baseline(1 week before treatment), the 1st month(4 weeks after baseline) | 
| Diffusion Tensor Imaging (DTI) - FA | Fractional anisotropy (FA) is a measurement used in DTI, which reflects the movement of water molecules. FA ranges from 0 to 1, the higher FA value may represent more intact axons.reflects the neural activity. | baseline(1 week before treatment), the 1st month(4 weeks after baseline) | 
| Verbal Learning & Memory: | Word list of Wechsler Memory Scale-III Face memory task | baseline(1 week before treatment), the 1st month(4 weeks after baseline) and the 6th month(24 weeks after baseline) | 
| Interleukin-1 | IL-1 | baseline(1 week before treatment), the 1st month(4 weeks after baseline) | 
| Interleukin-2 | IL-2 | baseline(1 week before treatment), the 1st month(4 weeks after baseline) | 
| Interleukin-6 | IL-6 | baseline(1 week before treatment), the 1st month(4 weeks after baseline) | 
| Interleukin-10 | IL-10 | baseline(1 week before treatment), the 1st month(4 weeks after baseline) | 
| Tumor necrosis factor | TNF-α | baseline(1 week before treatment), the 1st month(4 weeks after baseline) | 
| Interleukin-1β | IL-1β | baseline(1 week before treatment), the 1st month(4 weeks after baseline) | 
| C-Reactive protein | CRP | baseline(1 week before treatment), the 1st month(4 weeks after baseline) | 
| cortisol | cortisol | baseline(1 week before treatment), the 1st month(4 weeks after baseline) | 
| thyrotropin | TSH | baseline(1 week before treatment), the 1st month(4 weeks after baseline) | 
| Brain-derived neurotrophic factor | BDNF | baseline(1 week before treatment), the 1st month(4 weeks after baseline) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TMS, TBS