Clinical trial NCT05964036: pBFS-guided High-dose TMS Over DMPFC for Treatment-resistant Major Depressive Disorder
Official title: Personalized Brain Functional Sectors (pBFS)-Guided DMPFC With High-dose rTMS for Treatment-resistant Depressive Disorder: a Randomized, Double-blind, Sham-controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Depression
Major Depressive Disorder
Severe Depression
Keywords: transcranial magnetic stimulation, rTMS
DMPFC
pBFS
precision target
Lead sponsor: Changping Laboratory
Sponsor class: OTHER
First posted: 2023-07-27
Enrollment: 45
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: The investigators aim to evaluate the safety and efficacy of pBFS-guided DMPFC target and high-dose rTMS therapy for the treatment of patients with treatment-resistant depression

Detailed description: Repetitive transcranial magnetic stimulation (rTMS) is an established therapy for treatment-resistant depression. Currently, the FDA cleared the SAINT Neuromodulation System for the treatment of Treatment-Resistant Depression(TRD) over the left dorsolateral prefrontal cortex (DLPFC). This methodology has been effective in a short period of time for treatment-resistant depression. However, some patients may not be able to persist in completing the treatment because they cannot bear the pain during treatment. The dorsomedial prefrontal cortex (DMPFC) region is relatively posterior, and DMPFC as an intervention target has been proven to have antidepressant effects, and patients have better pain tolerance during treatment, which can be used as an alternative to DLPFC target, so it is urgent to explore the effectiveness and safety of high-dose iTBS targeting DMPFC in the treatment of depression.

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 blind manner in a 2:1 ratio to the active-rTMS group, and sham-rTMS group. Then all participants will undergo a 5-day rTMS modulation followed by two-week and four-week follow-up visits. Participants will keep a stable treatment regime during treatment and the four-week follow-up.

Eligibility criteria: Inclusion Criteria:

* DSM-5 diagnosis of depressive disorder, recurrent episodes;
* A total score of at least 20 on the HAMD-17 and Montgomery-Asberg Depression Rating Scale;
* Aged 18-65 years, female or male;
* Inadequate response to at least one antidepressant trial of adequate doses and duration;
* The MSM (Maudsley Staging Method) score ≥ 7;
* Stable antidepressant regimen for at least 4 weeks before treatment;
* Understand the trial and sign the informed consent.

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;
* The female of childbearing potential who plans to become pregnant during the trial, and 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.
* 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)
timeFrame: Baseline, Day 5
Secondary outcomes:
measure: Change in MADRS
timeFrame: Baseline, Day 5 (Immediate Post-treatment), 14 days Post-treatment, 28 days Post-treatment
measure: Change in Hamilton Depression Scale (HAMD-17)
timeFrame: Baseline, Day 5 (Immediate Post-treatment), 14 days Post-treatment, 28 days Post-treatment
measure: Change in Quick Inventory of Depressive Symptomatology Self-Report (QIDS_SR)
timeFrame: Baseline, Day 5 (Immediate Post-treatment), 14 days Post-treatment, 28 days Post-treatment
measure: cognitive change in Digit Symbol Substitution Test (DSST)
timeFrame: Baseline, Day 5 (Immediate Post-treatment)
measure: cognitive change in continuous performance test (CPT)
timeFrame: Baseline, Day 5 (Immediate Post-treatment)
measure: cognitive change in Trail-Making Test (TMT)
timeFrame: Baseline, Day 5 (Immediate Post-treatment)
measure: cognitive change in Digit Span Test (DST)
timeFrame: Baseline, Day 5 (Immediate Post-treatment)
measure: Safety estimated using SSI
timeFrame: Baseline, Day 5 (Immediate Post-treatment), 14 days Post-treatment, 28 days Post-treatment
measure: Safety estimated using YMRS
timeFrame: Baseline, Day 5 (Immediate Post-treatment), 14 days Post-treatment, 28 days Post-treatment
Other outcomes:
Locations:
city: Baoding
country: China
facility: Hebei Mental Health Center
state: Hebei
Study officials:
affiliation: Changping Laboratory
name: hesheng Liu
role: STUDY_CHAIR
References: