Major Depressive Disorder
Conditions
Brief summary
Background and Rationale With rapid economic development and increasing societal pressures, the incidence of neuropsychiatric disorders has risen annually, ranking as the leading cause of disability worldwide and imposing a severe societal burden. Among these, depressive disorders represent a primary contributor. However, the efficacy and accessibility of transcranial magnetic stimulation (TMS) for depression face significant challenges. Key limitations include: Low targeting accuracy with traditional localization methods. Limited clinical penetration of individualized precision paradigms . In this context, wearable repetitive TMS (wrTMS) technology offers a transformative solution. The rTMS-Tiny device, developed by the Institute of Automation, Chinese Academy of Sciences, exemplifies this innovation with the following features: Battery-powered with a pulse capacity exceeding 8,000 pulses per charge. Ultra-lightweight design: Total system weight \<3 kg, coil helmet \<2 kg (10% of conventional devices). Performance parity: Comparable efficacy to standard rTMS systems while enabling protocols like Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) . Advantages of rTMS-Tiny Portable Design and Wearable Application Ergonomically optimized helmet allows near-unrestricted daily activities during treatment . Streamlined Operational Workflow Simplified protocols significantly reduce clinician workload . Enhanced Treatment Tolerability Improved comfort increases treatment completion rates and long-term adherence, directly enhancing therapeutic outcomes . These advantages enable high-dose, intensive regimens (e.g., SAINT-like protocols) in routine clinical practice . Scientific Imperative for a Multicenter RCT A multicenter randomized controlled trial (RCT) of rTMS-Tiny is clinically and scientifically warranted to: Test two core hypotheses: Hypothesis 1: Efficacy of rTMS-Tiny in reducing depressive symptoms. Hypothesis 2: Safety of home-based rTMS-Tiny administration . Generate high-level evidence to advance neuromodulation into an era of precision, personalization, and artificial intelligence-driven therapy .
Interventions
DEVICErTMS-Tiny Treatment
Stimulation protocol using the rTMS-Tiny device with identical parameters to SNT: Stimulation mode Intermittent Theta-Burst Stimulation (iTBS) Burst composition: Each burst consists of 3 pulses at 50 Hz Train structure: 10 bursts repeated at 5 Hz per train (total train duration: 2 seconds) Inter-train interval: 8 seconds Session parameters Pulses per session: 1,800 pulses Session duration: 570 seconds (≈9.5 minutes) Inter-session interval: 50 minutes Daily frequency: 10 sessions per day Weekly schedule: 5 days per week Treatment course: 1 week (total 50 sessions) Total pulses per course: 1,800 pulses/session × 50 sessions = 90,000 pulses
DEVICESham Stimulation
The key difference lies in the use of a sham stimulation coil instead of the rTMS-Tiny active treatment coil.
Sponsors
Shanghai Mental Health Center
Ministry of Science and Technology of the People´s Republic of China
Peking University Sixth Hospital
The Central Hospital of Yongzhou
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1\. Inclusion Criteria 1. Demographics Aged 18-65 years, any gender. Minimum education: primary school completion (≥6 years of formal education). 2. Diagnostic and Severity Requirements Meet DSM-5 criteria for Major Depressive Disorder (MDD). Current moderate-to-severe depressive episode, defined by Hamilton Depression Rating Scale 17-item (HAMD-17) score ≥18 . 3. Pharmacological Stability Stable antidepressant regimen for ≥4 weeks prior to enrollment, restricted to SSRIs (Selective Serotonin Reuptake Inhibitors). Treatment-naïve patients permitted if no psychotropic medications used within the prior 4 weeks. Mandatory maintenance of the same regimen throughout the study and post-treatment follow-up. 4. Technical Feasibility Medically eligible for both structural MRI and resting-state functional MRI (fMRI) examinations. 2\.
Exclusion criteria
1. Psychiatric Comorbidities Any concurrent psychiatric diagnosis (e.g., autism spectrum disorder, severe cognitive impairment, epilepsy, mania, psychosis) . 2. Neurological Structural Abnormalities Structural brain lesions increasing seizure risk or disrupting neural connectivity (e.g., brain tumors, history of stroke). 3. Systemic Medical Conditions Unstable cardiovascular, respiratory, hepatic, renal diseases, or active malignancies. 4. Contraindications to Procedures TMS contraindications: Metallic implants, pacemakers, history of epilepsy. MRI contraindications: Ferromagnetic implants, claustrophobia requiring sedation. 5. Recent Neuromodulation Therapies Prior ECT (Electroconvulsive Therapy) or rTMS (repetitive Transcranial Magnetic Stimulation) within 3 months. History of neurosurgical interventions for depression (e.g., deep brain stimulation). 6）Special Populations Pregnancy, lactation, or planning pregnancy during the study. 7）Medication Instability Planned adjustments to pharmacotherapy during the study period. 3. Withdrawal and Discontinuation Criteria 1. Participant-Initiated Withdrawal Voluntary withdrawal: Participant withdraws consent (e.g., refusal to risk assignment to sham stimulation group). 2. Investigator-Initiated Withdrawal Non-compliance with inclusion criteria: Post-randomization discovery of ineligibility (e.g., symptom remission, medication non-adherence). Serious Adverse Events (SAEs): TMS-related SAEs (e.g., seizure, intractable headache, exacerbated suicidality). 3. Study Discontinuation Prespecified Efficacy Stoppage: Interim analysis at n=30/group showing superiority of active intervention (Cohen's d \>0.8) . Safety-Driven Discontinuation: Unacceptable risk profile (e.g., recurrent SAEs such as seizures or suicidality). Loss to Follow-Up: Trial termination if attrition rate exceeds pre-specified thresholds compromising statistical power (e.g., \>20% dropout).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 17-item Hamilton Depression Rating Scale (HAMD-17) Total Score | T1 (Baseline )Day 0, prior to the first rTMS session; T2 (Mid-peri-procedural period (~Month 6 ±2 weeks）)； T3 ( End of peri-procedural period (within 1 week of last session) )； T4 (4-week follow-up)； T5 (3-month follow-up)； T6 (6-month follow-up) | Depressive symptom severity was assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17; total score range, 0-52, with higher scores indicating more severe depression；Treatment Response Rate:≥50% reduction from baseline in HAMD-17 total score;Treatment Remission Rate:Post-treatment HAMD-17 Score \< 8) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | T1 (Baseline )Day 0, prior to the first rTMS session; T2 (Mid-peri-procedural period (~Month 6 ±2 weeks）)； T3 ( End of peri-procedural period (within 1 week of last session) )； T4 (4-week follow-up)； T5 (3-month follow-up)； T6 (6-month follow-up) | Depressive symptom severity assessed with the Montgomery-Asberg Depression Rating Scale (MADRS), a 10-item clinician-rated scale. The total score ranges from 0 (minimum) to 60 (maximum); higher scores indicate more severe depressive symptoms (worse outcome), and lower scores indicate improvement. |
Countries
China
Contacts
CONTACTXiaoyun Guo
Outcome results
None listed