TBS Over DLPFC in Elderly Refractory Depression

Efficacy of Bilateral Dorsolateral Prefrontal Theta-burst Stimulation in Elderly Refractory Depression: a Randomized Sham-controlled Study

The study aim to examine the effect of Thea-burst stimulation over bilateral dorsolateral prefrontal cortex (DLPFC) among patients with LLD on mood condition and relevant biomarkers.

Study Overview

• Status: Recruiting
• Conditions: Major Depression
• Intervention / Treatment: Device: TBS; Device: sham

Detailed Description

Thea-burst stimulation (TBS) is a novel form of rTMS, providing greater modulation effect on neural activity. So far, no study was conducted to use TBS as treatment in LLD. Therefore, we aim to examine the effect of TBS over bilateral dorsolateral prefrontal cortex (DLPFC) among patients with LLD on mood condition and relevant biomarkers. The study used a two-arm, parallel, double-blind, randomized, and sham-controlled design. We plan to enroll sixty patients with LLD, thirty for active intervention and thirty for sham-controlled group. An Magstim Rapid2 stimulator with eight-figure coil was used for stimulation. Location of brain area are based on bilateral DLPFC. 3-pulse 50-Hz bursts was given every 200ms (at 5 Hz) and an intensity of 80% active motor threshold was settled. We initially used cTBS (continuous TBS) over right DLPFC with 120-s train of uninterrupted bursts (1800 pulses) in each session per day. After that, we continuous use iTBS (intermittent TBS, iTBS) over left DLPFC with 2-s train of bursts was repeated every 10 s for a total of 570 s (1800 pulses). Each patient received daily stimulation for two weeks with total ten sessions. The primary outcomes were change of depression severity including response and remission rate. Secondary outcome were biomarkers related to depression. Assessments were administered at baseline, immediately after 5 and 10 sessions of stimulation, and 3 months after the completion of stimulation.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Che-Sheng Chu, MD; Phone Number: 72068 +886-7-3422121; Email: cschu@vghks.gov.tw

Study Locations

• Taiwan
  • Kaohsiung, Taiwan, 813
    • Recruiting
    • Department of Psychiatry, Kaohsiung Veterans General Hospital
    • Contact: Che-Sheng Chu, MD; Phone Number: 72068 +886-7-3422121; Email: cschu@vghks.gov.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 60 to 85 years
• Major depression disorder
• Under a stable dose of all psychotropic medication during the stimulation period.

Exclusion Criteria

• Having any current psychiatric comorbidity or history of substance dependence.
• Having active suicidal ideation currently.
• Having severe physical illness, recent and/or current unstable medical disorders.
• Having history of cancer or chemotherapy.
• Dementia or MMSE<24.
• Having TMS contraindicated (seizure disorder, history of seizures, metal in the head, pacemakers, history of craniotomy)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Experimental; We initially used cTBS (continuous TBS) over right DLPFC with 120-s train of uninterrupted bursts (1800 pulses) in each session per day. After that, we continuous use iTBS (intermittent TBS, iTBS) over left DLPFC with 2-s train of bursts was repeated every 10 s for a total of 570 s (1800 pulses).	Device: TBS; We initially used cTBS (continuous TBS) over right DLPFC with 120-s train of uninterrupted bursts (1800 pulses) in each session per day. After that, we continuous use iTBS (intermittent TBS, iTBS) over left DLPFC with 2-s train of bursts was repeated every 10 s for a total of 570 s (1800 pulses).
Placebo Comparator: Sham Comparator; Participants will receive sham (placebo) TBS treatment the same as experimental group	Device: sham; Participants will receive sham (placebo) TBS treatment the same as experimental group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hamilton Depression Rating Scale, HAM-D	The Ham-D is the most widely used clinician-administered depression assessment scale. The original version contains 17 items pertaining to symptoms of depression experienced over the past week. A score of 0-7 is generally accepted to be within the normal range (or in clinical remission), while a score of 20 or higher (indicating at least moderate severity) is usually required for entry into a clinical trial.	Change from baseline after 1, 2 weeks and three months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beck depression inventory, BDI-II	The BDI-II was a 1996 revision of the BDI. Participants were asked to rate how they have been feeling for the past two weeks. BDI-II also contains 21 questions, each answer being scored on a scale value of 0 to 3. Higher total scores indicate more severe depressive symptoms. The standardized cutoffs used as follows: 0-13: minimal depression; 14-19: mild depression; 20-28: moderate depression; 29-63: severe depression.	Change from baseline after 1, 2 weeks and three months
Beck anxiety inventory, BAI	The BAI, created by Aaron T. Beck and other colleagues, is a 21-question multiple-choice self-report inventory that is used for measuring the severity of anxiety in children and adults. The BAI contains 21 questions, each answer being scored on a scale value of 0 (not at all) to 3 (severely). Higher total scores indicate more severe anxiety symptoms. The standardized cutoffs are as follows: 0-7: minimal anxiety; 8-15: mild anxiety; 16-25: moderate anxiety; 26-63: severe anxiety.	Change from baseline after 1, 2 weeks and three months

Collaborators and Investigators

• Sponsor: Kaohsiung Veterans General Hospital.
• Investigators: Principal Investigator: Che-Sheng Chu, MD, Kaohsiung Veterans General Hospital.

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2022
• Primary Completion (Anticipated): July 31, 2024
• Study Completion (Anticipated): July 31, 2024

Study Registration Dates

• First Submitted: May 2, 2021
• First Submitted That Met QC Criteria: May 3, 2021
• First Posted (Actual): May 4, 2021

Study Record Updates

• Last Update Posted (Estimate): January 16, 2023
• Last Update Submitted That Met QC Criteria: January 13, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant
• Other Study ID Numbers: Kaohsiung VGHKS

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