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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Late Life Depression
• Intervention / Treatment: Device: Transcranial magnetic stimulation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 125
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Shwu-Hua Lee; Phone Number: 3839 03-3281200; Email: shlee@cgmh.org.tw
• Study Contact Backup: Name: hsueh-ching tsai, bachelor; Phone Number: 3839 03-3281200; Email: stacy.tsai409@gmail.com

Study Locations

• Taiwan
  • Guishan
    • Taoyuan, Guishan, Taiwan, 333423
      • Recruiting
      • "MAGSTIM" Repetitive transcranial magnetic stimulator(rTMS) System
      • Contact: Shwu-Hua Lee, Bachelor; Phone Number: 03-3277859 0975365654; Email: shlee@cgmh.org.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age > 50 years.
2. Major depressive disorder (MDD).
3. Right handiness
4. 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:

1. Inability to provide informed consent.
2. Dementia, as defined by MoCA 23/24. Other major mental or current psychotic symptoms
3. Active current suicidal intent as evidenced or the endorsement of an actual attempt, interrupted attempt,
4. Have known preexisting noise-induced hearing loss, concurrent treatment with ototoxic medications, or with cochlear implants are on medications known to lower seizure threshold.
5. Alcohol or other substances abuse of or dependence on within the past 3 months Organic brain, head trauma,
6. Elevated risk of seizure due to TBI
7. Participation in concurrent clinical trial
8. Non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview).
9. 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
10. Mental implement in the brain, claustrophobia
11. Ever received ECT, TMS Consent procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: dorsolateral prefrontal cortex; 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; Transcranial magnetic stimulation
Experimental: ventrolateral prefrontal cortex; 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; Transcranial magnetic stimulation
Placebo Comparator: sham comparator; 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; Transcranial magnetic stimulation

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Investigators: Study Chair: Shwu-Hua Lee, ChungGung memorial hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2021
• Primary Completion (Anticipated): July 31, 2023
• Study Completion (Anticipated): July 31, 2024

Study Registration Dates

• First Submitted: July 2, 2021
• First Submitted That Met QC Criteria: August 17, 2021
• First Posted (Actual): August 18, 2021

Study Record Updates

• Last Update Posted (Actual): November 10, 2022
• Last Update Submitted That Met QC Criteria: November 7, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: TMS; TBS
• Additional Relevant MeSH Terms: Behavioral Symptoms; Self-Injurious Behavior; Suicide; Depression; Suicidal Ideation
• Other Study ID Numbers: 202002467A3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No