Clinical trial NCT05948839: pBFS Guided rTMS Over DMPFC for Treatment-Resistant Depression
Official title: Personalized Brain Functional Sector-guided rTMS Therapy Targeting DMPFC for Treatment-resistant Depression
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Treatment Resistant Depression
Major Depressive Disorder
Keywords: Treatment Resistant Depression, TRD
Moderate Depression, MDD
personalized neuromodulation
Personalized Brain Functional Sectors
Lead sponsor: Changping Laboratory
Sponsor class: OTHER
Collaborators: name: Hebei Mental Health Center
name: Shandong Daizhuang Hospital
name: West China Hospital
name: The Second Affiliated Hospital of Xinxiang Medical University
First posted: 2023-07-17
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Investigators aim to evaluate the safety and efficacy of pBFS-guided rTMS therapy targeting DMPFC for patients with treatment-resistant depression

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Montgomery-Asberg Depression Rating Scale (MADRS) scores from baseline to Immediate Post-treatment
timeFrame: Baseline and Day 21(Immediate Post-treatment)]
Secondary outcomes:
measure: Remission and response rates were estimated using Montgomery-Asberg Depression Rating Scale(MADRS)
timeFrame: Baseline, Day 21 (Immediate Post-treatment)
measure: Remission and response rates were estimated using Hamilton Depression Rating Scale (HAMD-17)
timeFrame: Baseline, Day 21 (Immediate Post-treatment)
measure: Changes in the MADRS from baseline to each visit
timeFrame: Baseline, Day 21 (Immediate Post-treatment), 3-week Post-treatment, 9-week Post-treatment
measure: Changes in the HAMD-17 from baseline to each visit
timeFrame: Baseline, Day 21 (Immediate Post-treatment), 3-week Post-treatment, 9-week Post-treatment
measure: cognitive changes from baseline to day 21(Immediate Post-treatment)
timeFrame: Baseline, Day 21 (Immediate Post-treatment)
Other outcomes:
Locations:
city: Baoding
country: China
facility: Hebei Mental Health Center
state: Hebei
city: Jining
country: China
facility: Shandong Daizhuang Hospital
city: Xinxiang
country: China
facility: The Second Affiliated Hospital of Xinxiang Medical University
Study officials:
affiliation: Changping Laboratory
name: Hesheng Liu, Ph.D.
role: STUDY_CHAIR
References: