This study aims to assess the feasibility, safety, acceptability, and preliminary efficacy trends of a Magnetic Resonance Imaging-guided Repetitive Transcranial Magnetic Stimulation (rTMS) intervention for adolescent depression through a pilot clinical trial. The findings will inform the design and optimization of subsequent formal randomized controlled trials, providing essential evidence for their execution.
This study is a randomized, double-blind, controlled pilot trial aimed at evaluating the feasibility, safety, acceptability, and preliminary efficacy trends of Magnetic Resonance Imaging-guided Repetitive Transcranial Magnetic Stimulation (rTMS) for the treatment of adolescent depression. Adolescents diagnosed with Major Depressive Disorder (MDD) will be randomly assigned in a 1:1:1 ratio to one of three groups: the experimental target rTMS treatment group, the conventional target rTMS treatment group, and the sham stimulation group. All three groups will receive 4 weeks of rTMS stimulation (10 Hz, 120% RMT) or sham stimulation intervention, using the Blackdolphin TMS Robot (SLD-YXRJ) by Xi'an Solide Brain Modulation Ltd. Co., with 20 sessions (administered on weekdays) in total. The intervention frequency and procedure will remain consistent across all groups. In the experimental target rTMS treatment group, participants will undergo MRI-guided identification of the left dorsolateral prefrontal cortex (DLPFC) region, where the voxel most negatively correlated with the functional connectivity of the subgenual anterior cingulate cortex (sgACC) will serve as the stimulation target. In the conventional target rTMS treatment group, participants will receive MRI-guided stimulation at the left DLPFC location. Participants in the sham stimulation group will receive a placebo treatment, simulating the rTMS procedure without generating an effective magnetic field output. Primary outcomes include feasibility and acceptability indicators, such as recruitment, retention, adherence, assessment completion, and tolerability, as well as preliminary clinical efficacy. Secondary outcomes include anxiety, suicidal ideation and behaviour, and global clinical improvement. Safety will be monitored throughout.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
45
Participants will undergo MRI-guided identification of the voxel in the left dorsolateral prefrontal cortex (DLPFC) that is most negatively correlated with the functional connectivity of the subgenual anterior cingulate cortex (sgACC) as the stimulation site.
participants will receive MRI-guided stimulation at the left DLPFC location.
Participants will receive a sham stimulation treatment designed to simulate the rTMS procedure without generating an effective magnetic field output.
The First Affiliated Hospital of Chongqing Medical University
Chongqing, China
RECRUITINGRecruitment Feasibility (Number of Participants Enrolled)
The total number of participants successfully enrolled in this study will be recorded to assess recruitment feasibility. The goal is to recruit 45 participants (15 in each of the three groups) over a 2-year period.
Time frame: 2 years
Intervention adherence (number of participants who completed the full 20 treatment sessions)
This outcome measure will assess participants' adherence to the 20 sessions of transcranial magnetic stimulation. Adherence is defined as completing all 20 sessions. Adherence is calculated by dividing the number of participants who met this criterion by the total number of participants.
Time frame: Throughout the entire course of treatment (up to 1 month)
Retention Rate (Number of Participants Remaining at 6-Month Follow-up)
This outcome measure will assess the proportion of participants still enrolled in the study at the 6-month follow-up assessment. Retention rate is calculated as the number of participants who completed the 6-month assessment divided by the number of participants enrolled at baseline.
Time frame: Throughout the entire course of treatment (up to 1 month) and follow-up (up to 6 months)
Response rate and remission rate of depressive symptoms
Preliminary clinical efficacy will be assessed by change in the Children's Depression Rating Scale-Revised (CDRS-R) total score from baseline. CDRS-R is a clinician-rated scale used to assess the severity of depressive symptoms in children and adolescents. It consists of 17 items, and the total score ranges from 17 to 113. Higher scores indicate more severe depressive symptoms. Changes in CDRS-R total score from baseline will be assessed at the end of treatment and at follow-up visits. Response rate of depressive symptoms will be defined as a ≥50% reduction in CDRS-R total score from baseline, and remission rate of depressive symptoms will be defined as a CDRS-R total score ≤28.
Time frame: Baseline, throughout the entire course of treatment (up to 1 month) and follow-up (up to 6 months)
Incidence of Adverse Events and Serious Adverse Events
Adverse events, abbreviated as AEs, and serious adverse events, abbreviated as SAEs, will be assessed to evaluate the safety and tolerability of the intervention. An AE is defined as any unfavorable medical occurrence in a participant during the study period, regardless of whether it is considered related to the intervention. An SAE is defined as any adverse event that results in death, is life-threatening, requires hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, or is otherwise considered medically significant. The number and proportion of participants experiencing at least one AE or SAE will be recorded throughout the study period. The severity, outcome, and relationship to the intervention will also be documented.
Time frame: Throughout the entire course of treatment (up to 1 month) and follow-up (up to 6 months)
Change in BDI-II (Beck Depression Inventory-II) scores from baseline
The Beck Depression Inventory-II, abbreviated as BDI-II, is a 21-item self-report scale used to measure the severity of depressive symptoms. Each item is scored from 0 to 3, and the total score ranges from 0 to 63. Higher scores indicate more severe depressive symptoms. Changes in BDI-II total score from baseline will be assessed at the end of treatment and at follow-up visits.
Time frame: Baseline, throughout the entire course of treatment (up to 1 month) and follow-up (up to 6 months)
Change in HAMA score from baseline
The Hamilton Anxiety Rating Scale, abbreviated as HAMA, is a clinician-rated scale used to assess the severity of anxiety symptoms. It consists of 14 items covering both psychic anxiety and somatic anxiety symptoms. Each item is scored from 0 to 4, and the total score ranges from 0 to 56. Higher scores indicate more severe anxiety symptoms. Changes in HAMA total score from baseline will be assessed at the end of treatment and at follow-up visits.
Time frame: Baseline, throughout the entire course of treatment (up to 1 month) and follow-up (up to 6 months)
Change in SCARED (The Screen for Child Anxiety-Related Emotional Disorders) scores from baseline
The Screen for Child Anxiety Related Emotional Disorders, abbreviated as SCARED, is a self-report scale used to assess anxiety symptoms in children and adolescents. The total score ranges from 0 to 82, with higher scores indicating more severe anxiety symptoms. The change in SCARED total score from baseline will be calculated at each post-baseline assessment time point.
Time frame: Baseline, throughout the entire course of treatment (up to 1 month) and follow-up (up to 6 months)
Change in suicide risk from baseline on the C-SSRS (Columbia Suicide Severity Rating Scale)
The Columbia-Suicide Severity Rating Scale, abbreviated as C-SSRS, is a clinician-administered scale used to assess suicidal ideation and suicidal behavior. The C-SSRS Suicidal Ideation Severity Score ranges from 0 to 5, where 0 indicates no suicidal ideation and higher scores indicate more severe suicidal ideation. The change in C-SSRS Suicidal Ideation Severity Score from baseline will be calculated at each post-baseline assessment time point.
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Time frame: Baseline, throughout the entire course of treatment (up to 1 month) and follow-up (up to 6 months)
Change in PSQI (Pittsburgh Sleep Quality Index) scores from baseline
The Pittsburgh Sleep Quality Index, abbreviated as PSQI, is a self-report questionnaire used to assess sleep quality and sleep disturbances over the past month. The 19 self-rated items are used to generate seven component scores, including subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. Each component score ranges from 0 to 3, and the global PSQI score ranges from 0 to 21. Higher scores indicate poorer sleep quality. Changes in the global PSQI score from baseline will be assessed at the end of treatment and at follow-up visits.
Time frame: Baseline, throughout the entire course of treatment (up to 1 month) and follow-up (up to 6 months)
Change in CGI-S (Clinical Global Impressions-Severity Scales) scores from baseline
The Clinical Global Impression-Severity scale, abbreviated as CGI-S, is a clinician-rated scale used to assess the overall severity of illness at the time of evaluation. It is rated on a 7-point scale, ranging from 1 = normal, not at all ill to 7 = among the most extremely ill patients. Higher scores indicate greater illness severity. Changes in CGI-S score from baseline will be assessed at the end of treatment and at follow-up visits.
Time frame: Baseline, throughout the entire course of treatment (up to 1 month) and follow-up (up to 6 months)
Change in CGI-I (Clinical Global Impressions-Improvement Scales) scores from baseline
The Clinical Global Impression-Improvement scale, abbreviated as CGI-I, is a clinician-rated scale used to assess the overall change in a participant's clinical condition compared with baseline. It is rated on a 7-point scale, ranging from 1 = very much improved to 7 = very much worse. Lower scores indicate greater clinical improvement. CGI-I scores will be assessed at the end of treatment and at follow-up visits.
Time frame: Throughout the entire course of treatment (up to 1 month) and follow-up (up to 6 months)
Change in RRS (Ruminative Responses Scale)
The Ruminative Responses Scale, abbreviated as RRS, is a self-report scale used to assess the tendency to engage in ruminative thinking in response to depressed mood. The full version consists of 22 items, and each item is rated on a 4-point scale, ranging from 1 to 4. The total score ranges from 22 to 88. Higher scores indicate greater levels of rumination. Changes in RRS total score from baseline will be assessed at the end of treatment and at follow-up visits.
Time frame: Baseline, throughout the entire course of treatment (up to 1 month) and follow-up (up to 6 months)
Change in PedsQL 4.0 score from baseline
The Pediatric Quality of Life Inventory Version 4.0 Generic Core Scales, abbreviated as PedsQL 4.0, is a standardized questionnaire used to assess health-related quality of life in children and adolescents. It consists of 23 items covering four domains: physical functioning, emotional functioning, social functioning, and school functioning. Raw item scores are reverse-scored and linearly transformed to a 0 to 100 scale, with 0=100, 1=75, 2=50, 3=25, and 4=0. The total scale score is calculated as the mean of all answered items, with higher scores indicating better health-related quality of life. Changes in PedsQL 4.0 total score from baseline will be assessed at the end of treatment and at follow-up visits.
Time frame: Baseline, throughout the entire course of treatment (up to 1 month) and follow-up (up to 6 months)