pBFS Guided rTMS Over DMPFC for Treatment-Resistant Depression

Personalized Brain Functional Sector-guided rTMS Therapy Targeting DMPFC for Treatment-resistant Depression

Investigators aim to evaluate the safety and efficacy of pBFS-guided rTMS therapy targeting DMPFC for 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, has been shown to be 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 in a double-blind manner in a 2:1 ratio to the active rTMS group, or sham-control group. Then all participants will undergo a 21-day rTMS modulation and a three- and nine-week follow-up visit.

• Study Type: Interventional
• Enrollment (Estimated): 170
• 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
  • Jining, China
    • Recruiting
    • Shandong Daizhuang Hospital
    • Contact: Zhonggang Wang
  • Xinxiang, China
    • Recruiting
    • The Second Affiliated Hospital of Xinxiang Medical University
    • Contact: Yongfeng Yang
  • Hebei
    • Baoding, Hebei, China
      • Recruiting
      • Hebei Mental Health Center
      • Contact: Bing Li

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Hospitalized/outpatient patients aged 18-65 years (inclusive), male or female.
• Meet the diagnostic criteria of DSM-5(Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) for depression disorder without psychotic symptoms, and currently experiencing a recurrence episode.
• Total HAMD17 score ≥20 and total MADRS score ≥25 before randomization.
• Inadequate response to at least one antidepressant trial of adequate doses and duration.
• A stable antidepressant regimen for at least 4 weeks at a dose not lower than the prescribed range of drug use before randomization.
• Voluntarily participate in the trial and sign informed consent. Able to comply with the planned visit, examination and treatment plan, and other study procedures.

Exclusion Criteria:

• Meet DSM-5 diagnostic criteria for other mental disorders (such as schizophrenia spectrum disorders, bipolar and related disorders, neurodevelopmental disorders, neurocognitive disorders, or depressive disorders due to substances and/or medications, depressive disorders due to other medical problems, etc.);
• Patients with a cardiac pacemaker, cochlear implant, or other metal foreign body and any electronic equipment implanted in the body, patients with claustrophobia and other contraindications to magnetic resonance scanning, and patients with contraindications to rTMS treatment;
• Patients with serious or unstable diseases of the cardiovascular, liver, kidney, blood, endocrine, neurological system, and other systems or organs, especially those with organic brain diseases (such as ischemic stroke, cerebral hemorrhage, brain tumor, etc.) and a history of severe brain trauma as judged by the researcher;
• History of epilepsy (presence of at least 2 uninduced seizures more than 24 hours apart, or diagnosis of the epileptic syndrome, or seizures within the past 12 months); Or currently received medications or other treatments that will lower the seizure threshold;
• History of ECT, rTMS, VNS, DBS, tDCS, light therapy, or other physical therapy related to mental illness within 3 months;
• Currently receiving or planning to start formal cognitive or behavioral therapy, or systemic psychological therapy (interpersonal therapy, dynamic therapy, cognitive behavioral therapy, etc.) during the trial.
• Substance abuse or dependence (including alcohol, drugs, and other psychoactive substances) in the past 1 year;
• Female of childbearing potential who plans to become pregnant during the trial.
• Female that is pregnant or breastfeeding.
• Patients in any clinical trials of other drugs or physical therapy within 1 month before the screening.
• First-degree relatives have bipolar affective disorder.
• There is a significant risk of suicide (MADRS item 10 ≥ 5).
• Difficulty or inability to engage in normal communication, understand or follow instructions, and cooperate with treatment and evaluators.
• Investigators think that was inappropriate 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 a session of 1800 pulse.	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; 3 sessions of sham rTMS would be delivered to the left DMPFC daily, with a session of 1800 pulse.	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).	Baseline and Day 21(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 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 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 changes from baseline to day 21(Immediate Post-treatment)	Cognitive scores are measured using Chinese brief cognitive test (C-BCT), including Digit Symbol Substitution Test (DSST), continuous performance test (CPT), Trail-Making Test (TMT), Digit Span Test (DST)	Baseline, Day 21 (Immediate Post-treatment)

Collaborators and Investigators

• Sponsor: Changping Laboratory
• Collaborators: West China Hospital; The Second Affiliated Hospital of Xinxiang Medical University; Hebei Mental Health Center; Shandong Daizhuang Hospital
• Investigators: Study Chair: Hesheng Liu, Ph.D., Changping Laboratory

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2023
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: June 29, 2023
• First Submitted That Met QC Criteria: July 10, 2023
• First Posted (Actual): July 17, 2023

Study Record Updates

• Last Update Posted (Estimated): December 12, 2023
• Last Update Submitted That Met QC Criteria: December 11, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: personalized neuromodulation; Treatment Resistant Depression, TRD; Moderate Depression, MDD; 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: CPLMDDDM150

Drug and device information, study documents

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