The Effect of Theta-burst Stimulation on Serum BDNF

Antidepressant Effect of Prolonged Intermittent Theta-burst Stimulation on Serum Brain-derived Neurotrophic Factor Levels of Patients With Depression: A Randomized, Double-Blind, Sham-Controlled Study

The goal of this clinical trial is to investigate the effect of theta burst stimulation for depression and serum brain-derived neurotrophic factor (BDNF) in individuals with major depression. The main question it aims to answer is whether 10 sessions of theta burst stimulation can influence the serum level of BDNF.

Participants will be randomized into active group and sham group. Researchers will compare the level of BDNF in these groups.

Study Overview

• Status: Recruiting
• Conditions: Gambling Disorder
• Intervention / Treatment: Device: Theta Burst Stimulation

Detailed Description

There is an increasing evidence that the BDNF could be involved in the mode of action of antidepressants and, perhaps, of brain stimulation. Brain stimulation methods, such as electroconvulsive therapy (ECT) has been used to treat patients with severe depression and is reported to increase BDNF levels in blood. Numerous studies has demonstrated that repetitive transcranial magnetic stimulation (rTMS) as an alternative to ECT, produced the most robust antidepressant effects, and is the most widely applied treatment protocol for major depressive disorder (MDD). Theta-burst stimulation (TBS) is a novel form of rTMS, and has recently emerged as a method with the potential to produce similar anti-depressant effects much more rapidly than traditional repetitive TMS protocols. It is presumed that BDNF mediates the therapeutic benefits of brain rTMS, but previous results are contradictory.

Specific Aims:

The study is a four-week randomized, double-blind, sham-controlled study comparing pre- and post-treatment serum BDNF levels of patients with MDD, who receive active or sham of prolonged intermittent TBS (piTBS) treatment.

Method:

During the four-week double-blind phase of active or sham piTBS treatment, piTBS sessions are scheduled daily in a 5-day sequence for 10 sessions over two weeks. Symptomatic ratings and serum BDNF measurement are administered at baseline (W0, before brain stimulation), at the end of Week 2 brain stimulation treatments, and at the two-week follow-up after the treatment (Week 4). Otherwise, the symptomatic changes are also evaluated at the end of Week 1 brain stimulation. The study include sixty patients with major depression and all participants are randomly allocated (1:1) to groups receiving either active or sham piTBS group. The aim of the present study is to explore the effect of piTBS therapy on serum BDNF levels and change of depression symptom rating scale, as well as their associations in patients with MDD.

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

Contacts and Locations

• Study Contact: Name: Hu-Ming Chang; Phone Number: 0978052951; Email: DAU66@tpech.gov.tw

Study Locations

• Taiwan
  • Taipei CITY
    • Taipei, Taipei CITY, Taiwan, 105
      • Recruiting
      • Taipei City Hospital
      • Contact: Hu-Ming Chang; Phone Number: 0978052951; Email: DAU66@tpech.gov.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. age between 20 and 65 years;
2. fulfilling the Diagnostic and Statistical Manual version 5 (DSM-5) criteria of Major depressive disorder assessed by the Structured Clinical Interview

Exclusion Criteria:

1. Inability to provide informed consent or comprehend the study procedure;
2. A major psychiatric illness including schizophrenia spectrum disorder, bipolar spectrum disorder, and major depressive disorder with psychotic features.
3. A current DSM-5 diagnosis of substance use disorder except nicotine use disorder or the use of one to two low-potency benzodiazepine tablets for sleep impairment;
4. Have known preexisting noise-induced hearing loss, concurrent treatment with ototoxic medications, or with cochlear implants.
5. Unstable medical illness, including malignancy, uncontrolled diabetes mellitus, unstable cardiac disease or recent myocardial infarction, or cerebrovascular or cardiovascular risk factors that require intensive medical management
6. On medications known to lower seizure threshold (e.g., TCA, bupropion, clozapine)
7. Implants controlled by physiological signals, including pacemaker, implantable cardioverter defibrillator, cochlear implant.
8. Metallic objects in the head, including stenting, suture.
9. Elevated risk of seizure due to traumatic brain history, seizure history, and head trauma, intracranial lesion, and alcohol or benzodiazepines withdrawal syndrome, stimulant intoxication.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active arm; Prolonged iTBS sessions are scheduled daily in a 5-day sequence for 10 sessions over two weeks	Device: Theta Burst Stimulation; Theta Burst Stimulation
Sham Comparator: Sham arm; Sham stimulation sessions are scheduled daily in a 5-day sequence for 10 sessions over two weeks	Device: Theta Burst Stimulation; Theta Burst Stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in depression severity	Measured by Montgomery-Asberg Depression Rating Scale (MADRS)	Before intervention (week 0) and after intervention (week 2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in brain-derived neurotrophic factor (BDNF)	Serum level of BDNF	Before intervention (week 0) and after intervention (week 2)

Collaborators and Investigators

• Sponsor: Taipei City Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2023
• Primary Completion (Anticipated): June 1, 2026
• Study Completion (Anticipated): June 1, 2026

Study Registration Dates

• First Submitted: April 18, 2023
• First Submitted That Met QC Criteria: May 2, 2023
• First Posted (Estimate): May 11, 2023

Study Record Updates

• Last Update Posted (Estimate): May 11, 2023
• Last Update Submitted That Met QC Criteria: May 2, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Brain-Derived Neurotrophic Factor, Theta Burst Stimulation
• Additional Relevant MeSH Terms: Mental Disorders; Disruptive, Impulse Control, and Conduct Disorders; Gambling
• Other Study ID Numbers: TCHIRB-11003020

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