Neuronavigation Guided iTBS With Personalized Target for Depression

Research on the Efficacy and Brain Network Mechanism of Personalized Targeting Intermittent Theta Burst Stimulation (iTBS) Based on Functional Magnetic Resonance Imaging for the Treatment of Major Depressive Disorder

The study will compare the efficacy of intermittent Theta Burst Stimulation (iTBS) with DLPFC-pgACC personalized target for major depressive disorder (MDD) and explore possible brain network mechanisms. The stimulated targets will be located by magnetic resonance imaging (MRI) based on functional MRI based on functional connectivity respectively. This study aims to identify that functional connectivity targeted iTBS protocols on DLPFC-pgACC personalized target have a better antidepressant efficacy compared the sham group and certify that pgACC is an effective potential effector target.

Study Overview

• Status: Completed
• Conditions: Depression
• Intervention / Treatment: Combination product: iTBS combined with antidepressants; Combination product: sham iTBS combined with antidepressants

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shaan'xi
    • Xi'an, Shaan'xi, China, 710032
      • XijingH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 to 60 years old
• Meet the criteria of the Diagnostic and Statistical Manual of Mental Disorder- V of MDD, single or recurrent
• Meet the threshold on the total HAMD17 score of >17 at both screening and baseline visits
• Able to provide informed consent

Exclusion Criteria:

• any other current or past psychiatric axis-I or axis-II disorders
• severe physical illnesses
• psychotic symptoms, alcohol or drug abuse
• A history of neurological disorders including seizure, cerebral trauma
• MRI evidence of structural brain abnormalities
• Contraindications to MRI and rTMS
• Acute suicide
• Female that is pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: functional MRI-guided iTBS (pgACC-DLPFC); The stimulating site of the left DLPFC is targeted based on functional MRI, where the most negative functional connectivity with the left pgACC. The MNI coordinate is (-10, 42, 6).	Combination product: iTBS combined with antidepressants; Two sessions of prolonged iTBS (1800 pulses) per day over 10 days combined with antidepressants.
Sham Comparator: functional MRI-guided iTBS(sham group); The stimulating site of the left DLPFC is targeted based on functional MRI, where the most negative functional connectivity with the left pgACC. The MNI coordinate is (-10, 42, 6).	Combination product: sham iTBS combined with antidepressants; Two sessions of sham prolonged iTBS (1800 pulses) per day over 10 days combined with antidepressants.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the 17-Item Hamilton Rating Scale for Depression (HAMD-17) Score from Baseline to 4 weeks post treatment	The HAMD-17 total score comprises a sum of the 17 individual item scores. Each item is rated on a 3 points scale from 0 to 2. The Total Score can range from 0 to 52, and higher scores indicate a greater degree of depression.	baseline and 4-week post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Therapeutic response rate and remission rate	Response is defined as a reduction ≥ 50% on the HAMD-17 and remission is defined as a score <8 on the HAMD-17.	immediately post-treatment
Change in the Montgomery-Asberg Depression Rating Scale (MADRS) Score	MADRS total score comprises a sum of the 10 individual item scores. Each item is rated on a 7 point scale from 0 to 6. The Total Score can range from 0 to 60, and higher scores indicate a greater degree of depression.	baseline, immediately post-treatment and 2-week, 4-week and 8-week post-treatment
Change in the Beck Scale for Suicidal Ideation-Chinese Version (BSI-CV) Score	BSI-CV is a self-reported questionnaire with 19 items. Each item is rated on a 3 point scale from 0 to 2. Scores range from 0 to 48. Total score Scores of 0 - 16 indicate low risk for suicide and scores of 16 or greater indicate higher risk for suicide.	baseline, immediately post-treatment and 2-week, 4-week and 8-week post-treatment
Change in the Hamilton Anxiety Scale (HAMA) Score	HAMD total score comprises a sum of the 14 individual item scores. Each item is rated on a 5 point scale from 0 to 4. The Total Score can range from 0 to 56, and higher scores indicate a greater degree of anxiety.	baseline, immediately post-treatment and 2-week, 4-week and 8-week post-treatment
Change From Baseline Functional Connectivity to Immediately Post-treatment	The change in resting state fMRI functional connectivity of the pgACC to the default mode network and within the default mode network will be assessed.	baseline、immediately post treatment and 4-week post-treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in a Neuropsychological Test Battery from Baseline to immediately post-treatment	The Perceived Deficits Questionnaire - Depression (PDQ-D) is a brief patient-rated scale to assess subjective cognitive dysfunction in people with depression. The PDQ-D is a 20-item questionnaire and the total score ranger from 0 to 80, and higher scores indicate a greater degree of cognitive impairment. THINC-it® is a brief screening tool designed to measure cognition and determine whether cognitive functioning is impaired. Users can complete the cognitive screening in only 10-15 minutes. THINC-it® includes 4 objective cognitive tests (adapted from choice reaction time, 1-back working memory task, symbol digit coding, and Trails-B) and a subjective cognitive questionnaire (PDQ-5).	Pre-treatment to immediately post-treatment

Collaborators and Investigators

• Sponsor: Xijing Hospital

Publications and helpful links

General Publications

• Zheng K, Chen L, Wang H; DIRECT consortium; Li B, Chen B. Beyond depression symptoms: the default mode network as a predictor of antidepressant response. Npj Ment Health Res. 2026 Jan 16;5(1):2. doi: 10.1038/s44184-025-00182-2.
• Liu N, Zhao N, Tang N, Cai M, Zhang Y, Lv R, Zhang Y, Han T, Meng Y, Zang Y, Wang H. Safety and efficacy of individual target transcranial magnetic stimulation to stimulate the most negative correlate of DLPFC-pgACC in the treatment of major depressive disorder: study protocol of a double-blind, randomised controlled trial. BMJ Open. 2024 Nov 7;14(11):e081520. doi: 10.1136/bmjopen-2023-081520.

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2023
• Primary Completion (Actual): January 30, 2025
• Study Completion (Actual): February 28, 2025

Study Registration Dates

• First Submitted: September 25, 2022
• First Submitted That Met QC Criteria: October 9, 2022
• First Posted (Actual): October 13, 2022

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: depression; neuronavigation; intermittent Theta Burst Stimulation
• Additional Relevant MeSH Terms: Behavioral Symptoms; Behavior; Depression; Psychotropic Drugs; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Central Nervous System Agents; Antidepressive Agents
• Other Study ID Numbers: XJLL-KY20222111

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: After completion of the trial and publication of the relevant paper, the corresponding author can be contacted for individual participant data.

Drug and device information, study documents

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