Clinical trial NCT06350396: pBFS-guided rTMS Over DMPFC for Treatment-Resistant Depression
Official title: rTMS Intervention for DMPFC Treatment of Treatment-Resistant Depression Under the Guidance of Personalized Brain Functional Area Dissection (pBFS) Technology
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Treatment Resistant Depression
Major Depressive Disorder
Keywords: Treatment Resistant Depression
Major Depression, Moderate Depression, MDD
personalized neuromodulation
Personalized Brain Functional Sectors
Lead sponsor: Changping Laboratory
Sponsor class: OTHER
First posted: 2024-04-05
Enrollment: 270
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: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Montgomery-Asberg Depression Rating Scale (MADRS) scores from baseline to Immediate Post-treatment
timeFrame: Change in Montgomery-Asberg Depression Rating Scale (MADRS) scores from baseline to 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, and 6-month 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 change in Digit Symbol Substitution Test (DSST)
timeFrame: Baseline, Day 21 (Immediate Post-treatment)
measure: cognitive change in continuous performance test (CPT)
timeFrame: Baseline, Day 21 (Immediate Post-treatment)
measure: cognitive change in Trail-Making Test (TMT)
timeFrame: Baseline, Day 21 (Immediate Post-treatment)
measure: cognitive change in Digit Span Test (DST)
timeFrame: Baseline, Day 21 (Immediate Post-treatment)
Other outcomes:
Locations:
city: Hebei
country: China
facility: Hebei Mental Health Center
state: Baoding
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: Hohhot
country: China
facility: Inner Mongolia Mental Health Center
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: