pBFS-guided rTMS Over DMPFC for Treatment-Resistant Depression

rTMS Intervention for DMPFC Treatment of Treatment-Resistant Depression Under the Guidance of Personalized Brain Functional Area Dissection (pBFS) Technology

This study is a multicenter, randomized, double-blind, placebo-controlled trial aimed at exploring the effectiveness and safety of rTMS intervention with DMPFC targets guided by pBFS in patients with treatment-resistant depression.

Study Overview

• Status: Recruiting
• Conditions: Major Depressive Disorder; Treatment Resistant Depression
• Intervention / Treatment: Device: active rTMS treatment; Device: sham rTMS treatment

Detailed Description

Repetitive transcranial magnetic stimulation (rTMS) is an established therapy for treatment-resistant depression. The dorsomedial prefrontal cortex (DMPFC), which serves as a connection intermediary of the aberrant functional network in cognitive control and rumination in depression, is highly correlated with disease manifestations and post-treatment improvements through several studies involving neuroimaging and brain injury. Research has shown that the response of DMPFC to rTMS is more subject to improving the dimensions of anxiety and insomnia in depression. Therefore, exploring the novel target DMPFC is also beneficial for distinguishing disease dimensions in the future, thereby enabling personalized treatment and improving clinical treatment efficacy.

After being informed about the study and potential risks. All patients giving written informed consent will undergo a screening period to determine eligibility for study entry. At week 0, patients who meet the eligibility requirements will be randomized double-blind in a 1:1 ratio to the active rTMS group, or sham-control group. Then all participants will undergo a 21-day rTMS modulation and a 3-week, 9-week, and 6-month post-treatment follow-up visit.

• Study Type: Interventional
• Enrollment (Estimated): 270
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Meiling Li, Ph.D.; Phone Number: 010-80726688; Email: meilingli@cpl.ac.cn

Study Locations

• China
  • Chengdu, China
    • Not yet recruiting
    • West China Hospital, Sichuan University
    • Contact: Qiyong Gong
  • Hohhot, China
    • Recruiting
    • Inner Mongolia Mental Health Center
    • Contact: Dongsheng Lv
  • Jining, China
    • Not yet recruiting
    • Shandong Daizhuang Hospital
    • Contact: Zhonggang Wang
  • Xinxiang, China
    • Recruiting
    • The Second Affiliated Hospital of Xinxiang Medical University
    • Contact: Yongfeng Yang
  • Baoding
    • Hebei, Baoding, China
      • Recruiting
      • Hebei Mental Health Center
      • Contact: Lili Zhang

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• (1) Patients who meet the diagnostic criteria for depression in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and are not accompanied by psychiatric symptoms, with single or repeated episodes;
• (2) The Hamilton Depression Scale (HAMD) score for 17 items before randomization was ≥ 20 points, and the Montgomery Asberg Depression Rating Scale (MADRS) score was ≥ 20 points;
• (3) Individuals aged ≥ 18 and ≤ 65 years old, regardless of gender;
• (4) Currently, at least one antidepressant has been used for 6 weeks and the dosage used cannot be lower than the prescribed range of drug use;
• (5) The Maudsley Staging Method (MSM) assesses patients as having at least moderate refractory levels (MSM score ≥ 7);
• (6) Before randomization, the current antidepressant treatment regimen should be stable for at least 4 weeks, and the dosage used should not be lower than the prescribed range of drug use;
• (7) Having received education for 5 years or more;
• (8) Understand the experiment and sign an informed consent form.

Exclusion Criteria:

• (1) Meets the DSM-5 diagnostic criteria for other mental disorders, including schizophrenia spectrum disorders, bipolar and related disorders, neurodevelopmental disorders, neurocognitive disorders, or depression caused by substances and/or drugs, or depression caused by other medical issues;
• (2) Individuals with pacemakers, cochlear implants, or other metal foreign objects, as well as any electronic devices implanted in the body, contraindications for magnetic resonance imaging scans such as claustrophobia, and contraindications for rTMS treatment;
• (3) Concomitant history of epilepsy (with at least 2 non induced seizures with an interval of more than 24 hours, diagnosed with epilepsy syndrome, or having seizures within the past 12 months);
• (4) Individuals who have received modified electroconvulsive mECT, rTMS, or light therapy within 3 months;
• (5) Concomitant organic brain diseases (such as ischemic stroke, cerebral hemorrhage, brain tumors, etc.) and a history of severe brain injury;
• (6) Complicated with serious heart, liver, kidney diseases, diabetes and other serious physical diseases;
• (7) Women of childbearing age who are currently pregnant, breastfeeding, or planning or may become pregnant during the trial period;
• (8) Have a history of drug and alcohol abuse within the past year;
• (9) First degree relatives suffer from bipolar disorder;
• (10) There is a significant risk of suicide (the 10th item of the MADRS scale is ≥ 5 points);
• (11) Difficulty in verbal communication to the point of being unable to communicate normally, understand or follow instructions, and unable to cooperate with treatment and evaluation;
• (12) Currently participating in clinical trials of other drugs or physical therapies (such as deep brain stimulation (DBS), electroconvulsive therapy (ECT), rTMS);
• (13) The researchers believe it is not suitable to participate.

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 rTMS treatment; 3 sessions of active rTMS would be delivered to the left DMPFC daily, with 1800 pulse/session.	Device: active rTMS treatment; Participants will receive 3 sessions per day of 1800 pulses per session, lasting for 21 days. Individualized targets will be generated using the pBFS method.
Sham Comparator: sham control; The identical treatment parameters will be administered akin to the active rTMS treatment, albeit devoid of actual stimulation.	Device: sham rTMS treatment; The parameters in the sham arms are the same as the active stimulation groups. Stimulation was delivered by the same device as the active group fitted with a sham coil.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Montgomery-Asberg Depression Rating Scale (MADRS) scores from baseline to Immediate Post-treatment	The Montgomery-Asberg Depression Rating Scale (MADRS) is a validated instrument stratifying the severity of depressive episodes in adults. The MADRS has an overall score ranging from 0 (no depression) to 60 (worst depression).	Change in Montgomery-Asberg Depression Rating Scale (MADRS) scores from baseline to Immediate Post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Remission and response rates were estimated using Montgomery-Asberg Depression Rating Scale(MADRS)	The response is defined as a symptom improvement of ≥50% and remission is defined as a score ≤10 on MADRS	Baseline, Day 21 (Immediate Post-treatment)
Remission and response rates were estimated using Hamilton Depression Rating Scale (HAMD-17)	The Hamilton Depression Rating Scale (HAMD) is the most widely used clinician-administered depression assessment scale. The HAMD-17 version consists of 17 items，and has an overall score ranging from 0 (no depression) to 52 (worst depression). Higher scores represent higher depression severity. The response is defined as a symptom improvement of ≥50% and remission is defined as a score ≤7 on HAMD-17	Baseline, Day 21 (Immediate Post-treatment)
Changes in the HAMD-17 from baseline to each visit	The Hamilton Depression Rating Scale (HAMD) is the most widely used clinician-administered depression assessment scale. The HAMD-17 version consists of 17 items，and has an overall score ranging from 0 (no depression) to 52 (worst depression). Higher scores represent higher depression severity.	Baseline, Day 21 (Immediate Post-treatment), 3-week Post-treatment, 9-week Post-treatment
cognitive change in Digit Symbol Substitution Test (DSST)	Cognitive scores are measured using Chinese brief cognitive test (C-BCT), the DSST equires a subject to match symbols to numbers according to a key located on the top of the page	Baseline, Day 21 (Immediate Post-treatment)
cognitive change in continuous performance test (CPT)	CPT from the C-BCT measures a person's sustained and selective attention	Baseline, Day 21 (Immediate Post-treatment)
cognitive change in Trail-Making Test (TMT)	The TMT test from the C-BCT can provide information about visual search speed, scanning, speed of processing, mental flexibility, and executive functioning	Baseline, Day 21 (Immediate Post-treatment)
cognitive change in Digit Span Test (DST)	DST from the C-BCT is a measure of verbal short term and working memory that can be used in two formats, Forward Digit Span and Reverse Digit Span	Baseline, Day 21 (Immediate Post-treatment)
Changes in the MADRS from baseline to each visit	The MADRS has an overall score ranging from 0 (no depression) to 60 (worst depression). Higher scores represent higher depression severity.	Baseline, Day 21 (Immediate Post-treatment), 3-week Post-treatment, 9-week, and 6-month Post-treatment

Collaborators and Investigators

• Sponsor: Changping Laboratory
• Investigators: Study Chair: Hesheng Liu, Ph.D., Changping Laboratory

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2024
• Primary Completion (Estimated): December 30, 2024
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: April 1, 2024
• First Submitted That Met QC Criteria: April 1, 2024
• First Posted (Actual): April 5, 2024

Study Record Updates

• Last Update Posted (Actual): May 7, 2024
• Last Update Submitted That Met QC Criteria: May 6, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Treatment Resistant Depression; Major Depression, Moderate Depression, MDD; personalized neuromodulation; Personalized Brain Functional Sectors
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant
• Other Study ID Numbers: CPLTRDDM2024

Drug and device information, study documents

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