Major Depressive Disorder (MDD)
Conditions
Brief summary
The goal of this randomized clinical trial is to learn whether context-guided personalized intermittent theta burst stimulation (iTBS) works better than standard iTBS for adults with major depressive disorder. iTBS is a noninvasive treatment that uses magnetic pulses to stimulate specific areas of the brain. Participants will be assigned by chance to one of two treatment groups. The standard treatment group will receive iTBS at a commonly used target in the left dorsolateral prefrontal cortex after watching a neutral video. The personalized treatment group will receive iTBS at an individual brain target selected using magnetic resonance imaging data. Before each treatment session, participants in this group will watch a positive emotional video intended to activate brain functions related to the selected target. Both groups will receive five iTBS sessions per day for five consecutive treatment days. Participants will continue their stable antidepressant treatment during the study. The main question is whether context-guided personalized iTBS results in a higher treatment response rate than standard iTBS two weeks after treatment. Treatment response is defined as a reduction of at least 50% from baseline in the 17-item Hamilton Depression Rating Scale score. Researchers will also compare early changes in depression, anxiety and other clinical symptoms, changes in brain imaging measures, and any side effects. Clinical and brain imaging assessments will be conducted before and after the treatment course, and clinical symptoms will be assessed again two weeks after treatment.
Interventions
DEVICEContext-Guided Personalized Intermittent Theta Burst Stimulation
An individualized stimulation target in the left or right dorsolateral prefrontal cortex is selected using the participant's functional magnetic resonance imaging data. Before each stimulation session, the participant watches a positive emotional video intended to engage brain functions related to the selected target. Intermittent theta burst stimulation is delivered at 100% of the resting motor threshold. Each session delivers 1,800 pulses over approximately 10 minutes. Participants receive five sessions per day, with approximately 50 minutes between sessions, for five consecutive treatment days.
DEVICEStandard Left DLPFC Intermittent Theta Burst Stimulation
Intermittent theta burst stimulation is delivered to a standard treatment target in the left dorsolateral prefrontal cortex. Before each stimulation session, the participant watches a neutral video. Stimulation is delivered at 100% of the resting motor threshold. Each session delivers 1,800 pulses over approximately 10 minutes. Participants receive five sessions per day, with approximately 50 minutes between sessions, for five consecutive treatment days.
Sponsors
Capital Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Male or female outpatients or inpatients aged 18 to 55 years, inclusive. * Right-handed. * Diagnosis of major depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), confirmed using the Mini International Neuropsychiatric Interview (MINI). Both first and recurrent depressive episodes are eligible. * A 17-item Hamilton Depression Rating Scale (HAMD-17) total score of at least 14 at both screening and baseline. * At enrollment, participants may be antidepressant-free or may have received an antidepressant at no less than the minimum effective dose for at least 4 weeks. The antidepressant may be combined with no more than two other medications, and the type and dosage of medications must remain unchanged from enrollment until study completion. * At least primary school education and able to understand the study procedures and requirements. * Able to undergo magnetic resonance imaging and intermittent theta burst stimulation safely. * Voluntarily agrees to participate and provides written informed consent.
Exclusion criteria
* Serious or unstable medical or neurological illness. * Pregnancy or breastfeeding. * History of seizure, epilepsy, hydrocephalus, or central nervous system tumor. * Contraindication to magnetic resonance imaging, including claustrophobia, an electronic or metallic implant, or a non-removable metallic dental prosthesis. * Receipt of systematic modified electroconvulsive therapy, transcranial magnetic stimulation, deep brain stimulation, vagus nerve stimulation, or another physical neuromodulation treatment within 3 months before screening. * Excessive head motion during MRI scanning (rotation exceeding 3.0° and/or translation exceeding 3 mm) * Resting motor threshold remaining at or above 70% of the device maximum stimulator output after repeated testing, when the investigator considers continued treatment to present a safety concern.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Response Rate at 2-Week Follow-up Based on HAMD-17 | At 2 weeks after completion of treatment (Day 21 ± 2 days). | The treatment response rate is defined as the proportion of participants with a reduction of at least 50% from baseline in the total score of the 17-item Hamilton Depression Rating Scale (HAMD-17) at the 2-week follow-up. The HAMD-17 is a clinician-rated scale used to assess the severity of depressive symptoms, with lower scores indicating fewer depressive symptoms. Treatment response rates will be compared between the context-guided personalized iTBS arm and the standard left DLPFC iTBS arm. The HAMD-17 total score ranges from 0 to 52, with higher scores indicating greater depressive symptom severity. Change from baseline is calculated as the post-baseline score minus the baseline score, with negative values indicating improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Early Treatment Response Rate Based on HAMD-17 | Baseline to immediately after completion of the treatment intervention | Early treatment response is defined as a reduction of at least 20% from baseline in the total score of the 17-item Hamilton Depression Rating Scale (HAMD-17) immediately after completion of the treatment intervention. The outcome will be summarized as the proportion of participants meeting this response criterion in each treatment arm. Lower HAMD-17 scores indicate fewer depressive symptoms. The HAMD-17 total score ranges from 0 to 52, with higher scores indicating greater depressive symptom severity. Change from baseline is calculated as the post-baseline score minus the baseline score, with negative values indicating improvement. |
| Change From Baseline in HAMD-17 Factor Scores | Baseline, immediately after completion of treatment, and 2 weeks after completion of treatment | Changes from baseline in the prespecified factor scores of the 17-item Hamilton Depression Rating Scale (HAMD-17) will be assessed at the 2-week follow-up. For each factor, the change score will be calculated as the follow-up score minus the baseline score. A greater reduction indicates greater improvement in the corresponding depressive symptom domain. The HAMD-17 consists of 17 items; 9 items are scored from 0 to 4 and 8 items are scored from 0 to 2. The total score ranges from 0 to 52, with higher scores indicating greater depressive symptom severity. Change is calculated as the post-baseline score minus the baseline score; negative values indicate improvement. |
| Change From Baseline in QIDS-SR16 Total Score | Baseline, immediately after completion of treatment, and 2 weeks after completion of treatment | Changes from baseline in the total score of the 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR16) will be assessed immediately after completion of the treatment intervention and at the 2-week follow-up. Lower scores indicate fewer self-reported depressive symptoms. The QIDS-SR16 total score ranges from 0 to 27, with higher scores indicating greater depressive symptom severity. |
| Change From Baseline in HAMA Total Score | Baseline, immediately after completion of treatment, and 2 weeks after completion of treatment | Changes from baseline in the total score of the Hamilton Anxiety Rating Scale (HAMA) will be assessed immediately after completion of the treatment intervention and at the 2-week follow-up. The HAMA is a clinician-rated measure of anxiety symptom severity, with lower scores indicating fewer anxiety symptoms. The 14-item HAMA total score ranges from 0 to 56, with higher scores indicating greater anxiety symptom severity. |
| Incidence of Adverse Events | From the first treatment session through the 2-week follow-up after completion of treatment | The number and proportion of participants experiencing one or more adverse events will be recorded for each treatment arm. Adverse events may include headache, scalp discomfort, muscle twitching, transient mood changes, or other adverse events occurring during the treatment and follow-up periods. |
Countries
China
Contacts
CONTACTZhi Yang, PhD
PRINCIPAL_INVESTIGATORZhi Yang, PhD
Beijing Anding Hospital, Capital Medical University
Outcome results
None listed