The Mechanisms of Underlying Accelerated Repetitive Transcranial Magnetic Stimulation for Treatment-resistant Depression

The Mechanisms of Underlying Accelerated Repetitive Transcranial Magnetic Stimulation for Treatment-resistant Depression Via Reelin-Apoer2-NMDAR Pathway- Mediated Synaptic Plasticity

In this project, the investigators evaluate an accelerated schedule of repetitive transcranial magnetic stimulation for treatment-resistant depression. The investigators focuse on participants' brain activity and blood markers (Reelin, Apoer2, NMDAR, BDNF, exosomes and so on) to deepen the understanding of the mechanism of accelerated rTMS for treatment-resistant depression.

Study Overview

• Status: Recruiting
• Conditions: Treatment-resistant Depression
• Intervention / Treatment: Device: active iTBS; Device: sham rTMS

Detailed Description

In this project, the investigator evaluate an accelerated schedule of repetitive transcranial magnetic stimulation for treatment-resistant depression. Patients were included in two groups and received an accelerated stimulation or sham treatment. The changes of neuroimaging and biomarkers at baseline, 5 days after treatment and 1 month after treatment are evaluated. The investigators focuse on participants' brain activity and blood markers (Reelin, Apoer2, NMDAR, BDNF, exosomes and so on) to deepen the understanding of the mechanism of accelerated rTMS for treatment-resistant depression.

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

Contacts and Locations

• Study Contact: Name: Manli Huang, M.D; Phone Number: 86 13957162975; Email: huangmanli@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • The First Affiliated Hospital of Zhejiang University
      • Contact: Manli Huang, M.D; Phone Number: 86 13957162975; Email: huangmanli@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The current episode met the DSM-5 diagnostic criteria for major depression in patients with first-episode or relapsed unmedicated depression without psychotic symptoms.
2. 24-item Hamilton Depression Scale (HAMD-24) ≥ 20.
3. Age 18-45 years, regardless of gender.
4. Right-handedness.
5. Han Chinese.
6. Signed a written informed consent, willing to participate in the study and be evaluated.

Exclusion Criteria:

1. Co-morbid other mental disorders, including: schizophrenia, mental retardation, substance dependence, etc.
2. Patients with metal objects in the body or with other contraindications to MRI scanning
3. Patients with severe or unstable somatic diseases
4. Women during pregnancy or lactation, and women of childbearing age with positive urine HCG test results during the screening period
5. Other conditions that, in the opinion of the investigator, exist that make participation in this clinical trial inappropriate.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: active iTBS; The active group of TRD will receive the accelerated intermittent TBS(iTBS).The iTBS cycles including 10 bursts of three pulses at 50 Hz were delivered in 2-second trains. Each iTBS session comprised 60 x 2 second trains, with an 8-second intertrain interval and total duration of 10-minutes.Treatment sessions were administered hourly 10 times a day totaling 18,000 pulses/day. Patients received this treatment protocol for 5 consecutive days (90,000 pulses in total).	Device: active iTBS; Participants in the active stimulation group will receive the accelerated intermittent TBS to left DLPFC. The L-DLPFC will be targeted utilizing the neuronavigation system. Stimulation intensity will be standardized at 90% of RMT. Stimulation will be delivered to the L-DLPFC using an NTK-TMS-II100 TMS device,is compatible with the Brainsight TMS navigation system.
Sham Comparator: sham rTMS; The sham group of TRD will receive sham rTMS stimulation.	Device: sham rTMS; The parameters in the sham arm will be as above with the internal randomization of the device internally switching to sham in a blinded fashion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in remission rate of Hamilton Depression Scale (24-items) (HAM-D24) score after treatment.	The Hamilton Depression Scale (24-items) (HAM-D24), is a 24 item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. Higher HAM-D24 score indicates more severe depression, and each item yields a score of 0 to 4. Remission is defined as HAM-D24 ≤8.	Baseline, 5-day, 1-month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in response rate of Hamilton Depression Scale (24-items) (HAM-D24) score after treatment.	The Hamilton Depression Scale (24-items) (HAM-D24), is a 24 item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. Higher HAM-D24 score indicates more severe depression, and each item yields a score of 0 to 4. Response is defined as a reduction of >/=50% of HAM-D24 baseline score.	Baseline, 5-day, 1-month
Change in the rate of Beck Scale of Suicidal Ideation score after treatment.	Beck Scale of Suicidal Ideation(BSI) is a 21-item self-report instrument that detects and measures the intensity of a patient's specific attitudes, behaviors, and suicide plans during the past week.	Baseline, 5-day, 1-month
Change in the rate of Hamilton Anxiety Scale score after treatment.	Hamilton Anxiety Scale (HAMA) is a 17 item diagnostic questionnaire used to measure the severity of anxiety episodes in patients	Baseline, 5-day, 1-month

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2023
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2026

Study Registration Dates

• First Submitted: October 26, 2022
• First Submitted That Met QC Criteria: November 1, 2022
• First Posted (Actual): November 7, 2022

Study Record Updates

• Last Update Posted (Estimate): January 13, 2023
• Last Update Submitted That Met QC Criteria: January 12, 2023
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Treatment-resistant Depression; Repeated transcranial magnetic stimulation; Prefrontal-hippocampal circuit; Reelin; Synaptic plasticity
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant
• Other Study ID Numbers: 82271562

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