Feasibility, Safety, and Preliminary Clinical Efficacy of Magnetic Resonance Imaging-guided Repetitive Transcranial Magnetic Stimulation (rTMS) in Adolescents With Depression: A Randomized, Double-Blind, Controlled Pilot Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Recruitment Feasibility (Number of Participants Enrolled)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 12 - 18
- •Diagnosis of major depressive disorder (MDD) according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), confirmed through the Kiddie Schedule for Affective Disorders and Schizophrenia - Present and Lifetime version (K-SADS-PL), currently in a depressive episode
- •Score≥40 on the CDRS-R
- •Stable pharmacological treatment: At least 4 weeks of stable psychiatric medication use prior to enrollment, with continuation of the same psychiatric medication regimen throughout the study.
排除标准
- •Psychiatric comorbidities other than anxiety disorders
- •Depression with psychotic symptoms
- •Young Mania Rating Scale (YMRS) score >13
- •A history of neurological disorders (e.g., epilepsy, brain injury) or severe somatic diseases (e.g., thyroid disorders, lupus, diabetes, pulmonary, hepatic, or renal impairment, major trauma)
- •Patients currently using anticonvulsants or high-dose benzodiazepines
- •A history of electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), or other neuromodulation treatments
- •A history of alcohol or substance abuse or dependence
- •Women who are pregnant or breastfeeding
- •Current high suicide risk
- •Potential complicating factors related to transcranial magnetic stimulation, such as scalp conditions or perforations that may affect magnetic field delivery
- •Contraindications to MRI
研究组 & 干预措施
Experimental target rTMS treatment group
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. Repetitive transcranial magnetic stimulation (rTMS) (10 Hz, 120% RMT) will be administered using the Blackdolphin TMS Robot device (model SLD-YXRJ) by Xi'an Solide Brain Modulation Ltd. Co., with 20 sessions over 4 weeks (treatment administered on weekdays).
干预措施: Experimental target rTMS treatment (Device)
Conventional target rTMS treatment group
Participants will receive MRI-guided stimulation at the left DLPFC location. Repetitive transcranial magnetic stimulation (rTMS) (10 Hz, 120% RMT) will be administered using the Blackdolphin TMS Robot device (model SLD-YXRJ) by Xi'an Solide Brain Modulation Ltd. Co., with 20 sessions over 4 weeks (treatment administered on weekdays).
干预措施: Conventional target rTMS treatment (Device)
Sham stimulation treatment group
Participants will receive a sham stimulation treatment designed to simulate the rTMS procedure without generating an effective magnetic field output. The intervention will use a dedicated sham stimulation coil, which is identical in appearance, operation, and stimulation protocol to the experimental group. This coil is designed to maintain the same auditory and tactile sensations as the active stimulation but is equipped with an electromagnetic shielding structure or an internal reverse coil arrangement to effectively prevent magnetic flux from penetrating the skull, ensuring no actual neuromodulatory effects.
干预措施: Sham stimulation treatment (Device)
结局指标
主要结局
Recruitment Feasibility (Number of Participants Enrolled)
时间窗: 2 years
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.
Intervention adherence (number of participants who completed the full 20 treatment sessions)
时间窗: Throughout the entire course of treatment (up to 1 month)
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.
Retention Rate (Number of Participants Remaining at 6-Month Follow-up)
时间窗: Throughout the entire course of treatment (up to 1 month) and follow-up (up to 6 months)
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.
Response rate and remission rate of depressive symptoms
时间窗: Baseline, throughout the entire course of treatment (up to 1 month) and follow-up (up to 6 months)
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.
Incidence of Adverse Events and Serious Adverse Events
时间窗: Throughout the entire course of treatment (up to 1 month) and follow-up (up to 6 months)
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.
次要结局
- Change in BDI-II (Beck Depression Inventory-II) scores from baseline(Baseline, throughout the entire course of treatment (up to 1 month) and follow-up (up to 6 months))
- Change in HAMA score from baseline(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(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)(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(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(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(Throughout the entire course of treatment (up to 1 month) and follow-up (up to 6 months))
- Change in RRS (Ruminative Responses Scale)(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(Baseline, throughout the entire course of treatment (up to 1 month) and follow-up (up to 6 months))
研究者
Xinyu Zhou
professor
First Affiliated Hospital of Chongqing Medical University