Neuroimaging Biomarker-guided Personalized High-Definition Transcranial Direct Current Stimulation (HD-tDCS) Treatment for Major Depressive Episode in Adolescents With Mood Disorders: A Randomized Controlled Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Change from baseline in depressive symptoms assessed by Hamilton depression rating scale 17 items (HAMD-17) at week 1 and week 2.
研究概览
简要总结
Adolescents with mood disorders experiencing major depressive episode have poor efficacy of medication treatment. High-Definition Transcranial Direct Current Stimulation (HD-tDCS) has been proven adjuvant efficacy in patients with major depressive episode. However, the optimal evidence-based stimulation parameters have not been clearly defined, which greatly limits the efficacy of HD-tDCS in the treatment of major depressive episode.This trial will compare a novel form of accurate and personalized HD-tDCS treatment protocol guided by neuroimaging biomarkers to the routine stimulation(stimulation target is L-DLPFC, central electrode is anode).The personalized selection of stimulation site, central electrode polarity will be determined by neuroimaging biomarkers. The study aims to propose a novel personalized neuroimaging-guided HD-tDCS strategy, to evaluate the efficacy and safety of the treatment, further to understand the biological mechanism of the personalized HD-tDCS treatment.
详细描述
Mood disorders, including mainly bipolar disorder (BD) and major depressive disorder (MDD), have become the primary health problem and one of the leading causes of functional disability in adolescents . In China, the incidence of mood disorders such as BD and MDD in adolescence has increased rapidly in recent years. Particularly, patients with mood disorder currently experiencing major depressive episode have high risk of suicide, and pharmacological treatment showed poor efficacy to such depressive patients. Mood disorders with major depressive episode have become one of the major threats to the mental health of adolescents in China. Therefore, it is of great significance to explore a series of early intervention strategies for adolescents with major depressive episode. HD-tDCS is a non-invasive brain stimulation treatment strategy with mild side effects. The set of stimulation parameters often has a vital impact on the final clinical efficacy of HD-tDCS treatment. Several clinical trials have reported the efficacy and safety of HD-tDCS on treatment major depression disorder. However, the evidence-based optimal targets and other stimulation parameters have not been clearly defined, which greatly limits the efficacy of HD-tDCS in the treatment of major depressive episode. To date, there is no large randomized clinical trial (RCT) exploring an optimization of HD-tDCS on adolescents with major depressive episode. This study is a randomized controlled trial aiming at assessing the efficacy and safety of a novel personalized HD-tDCS treatment protocol compared to routine stimulation for major depressive episode in adolescents with mood disorders. Participants will be assigned randomly (1:1) to the personalized HD-tDCS group or the routine HD-tDCS group. Participants will be treated with 20 sessions (2 sessions per day) HD-tDCS treatment. The stimulation parameters of routine HD-tDCS group are: current=2 mA, duration=20 min, stimulation target=L-DLPFC, central electrode=anode. The stimulation parameters of personalized HD-tDCS group are current=2 mA and duration=20 min, while the stimulation target and central electrode polarity are based on neuroimaging biomarkers extracted via machine learning. Participants in both groups will maintain the stable drug regimen during the HD-tDCS trial.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 13 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Between 13 and 18 years of age;
- •Participants fulfill the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnostic criteria for major depressive disorder (MDD) or bipolar disorder (BD);
- •Participants are assessed by the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K-SADS-PL);
- •A current moderate or severe depressive episode defined by HAMD>17;
- •Participants receive a stable psychotropic medication regimen prior to randomization to the trial and patient will be willing to remain on the stable regimen during the HD-tDCS treatment phase;
- •All participants provided written informed consent by themselves or their guardians after the detailed description of the study.
排除标准
- •Prior rTMS, tDCS, electroconvulsive therapy (ECT) application or standard psychological therapy within 6 months prior to screening;
- •Comorbidity of other DSM-IV axis I disorders or personality disorders;
- •Judged clinically to be at serious suicidal risk;
- •Diabetes mellitus, hypertension, vascular and infectious diseases and other major medical comorbidities;
- •Unstable medical conditions, e.g., severe asthma;
- •Neurological disorders, e.g., history of head injury with loss of consciousness for ≥ five minutes, cerebrovascular diseases, brain tumors and neurodegenerative diseases;
- •Mental retardation or autism spectrum disorder;Contraindications to MRI (e.g., severe claustrophobia, pacemakers, metalimplants);
- •Contraindications to HD-tDCS (e.g., scalp rupture, cranial plates, history of seizure,electroencephalogram (EEG) test suggesting high risk of seizure, known brain lesion);
- •Current drug/alcohol abuse or dependence;Pregnant or lactating female.
研究组 & 干预措施
Personalized HD-tDCS
The experimental arm will receive the personalized HD-tDCS treatment with parameters as follows:
- Neuroimaging biomarker-guided personalized selection for central electrode polarity: anode or cathodal;
- Neuroimaging biomarker-guided personalized selection for stimulation site: dorsalmedial prefrontal cortex or occipital cortex;
- Schedule: 2 sessions per day, five days per week for a total of 20 sessions over 2 weeks.
干预措施: High-Definition Transcranial Direct Current Stimulation (HD-tDCS) (Device)
Personalized HD-tDCS
The experimental arm will receive the personalized HD-tDCS treatment with parameters as follows:
- Neuroimaging biomarker-guided personalized selection for central electrode polarity: anode or cathodal;
- Neuroimaging biomarker-guided personalized selection for stimulation site: dorsalmedial prefrontal cortex or occipital cortex;
- Schedule: 2 sessions per day, five days per week for a total of 20 sessions over 2 weeks.
干预措施: Antipsychotics, mood stabilizers, etc. (Drug)
Routine HD-tDCS
Routine stimulation arm will receive the same scheme of HD-tDCS, but the stimulation target is L-DLPFC with anode as central electrode.
干预措施: High-Definition Transcranial Direct Current Stimulation (HD-tDCS) (Device)
Routine HD-tDCS
Routine stimulation arm will receive the same scheme of HD-tDCS, but the stimulation target is L-DLPFC with anode as central electrode.
干预措施: Antipsychotics, mood stabilizers, etc. (Drug)
结局指标
主要结局
Change from baseline in depressive symptoms assessed by Hamilton depression rating scale 17 items (HAMD-17) at week 1 and week 2.
时间窗: Baseline, week 1 and week 2
The HAMD-17 scale has 17 items. The total score ranges from 0-52, with higher score indicating more severe depressive symptoms. A total score of 0-7 is considered to be normal. Scores of 17 or higher indicate moderate, severe, or very severe depression.
Change from baseline in neurocognitive function using Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) test at week 2.
时间窗: Baseline and week 2.
RBANS is a test for identifying and characterizing abnormal cognitive decline for patients with neuropsychiatric disorders. The RBANS is comprised of five domains, which are Immediate Memory, Visuospatial /Constructional,Language, Attention and Delayed Memory. The total score of RBANS range from 40-160, with 160 referring to higher cognitive functioning. A score of 95-115 is in the average range; score of 70-85 mild to moderate cognitive impairment; score \<70 moderate to severe impairment.
Change from baseline in resting-state magnetic resonance imaging (MRI) , diffusion tensor imaging (DTI) and structural (T1-weighted) imaging at weeks 1 and 2.
时间窗: Baseline, week 1 and week 2.
Participants will undergo MRI scans prior to beginning HD-tDCS treatment (week 0) and after completing 10 sessions of HD-tDCS treatment (weeks 1) and after completing 20 sessions of HD-tDCS treatment (weeks 2). This allows for a comprehensive examination of changes from baseline in functional activity, DTI and structural changes in the brain at weeks 1 and 2.
次要结局
- Change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) at week 1 and week 2.(Baseline, week 1 and week 2.)
- Change from baseline in the Clinical Global Impression-Severity scale (CGI-S) at week 1 and week 2.(Baseline, week 1 and week 2.)
- Electroencephalogram - Beta Waves (13-30 Hz)(Baseline)
- Change from baseline in neurocognitive function using Facial Emotion Perception Test (FEPT) at week 2.(Baseline and week 2.)
- Change from baseline in acoustic features.(Baseline, week 1 and week 2.)
- Change from baseline in depressive symptoms assessed by the Patient Health Questionnaire-9 (PHQ-9; range: 0-27) at baseline, week 1 and week 2.(Baseline, week 1 and week 2.)
- Change from baseline in anxiety symptoms assessed by the Generalized Anxiety Disorder-7 (GAD-7, range: 0-21) at baseline, week 1 and week 2.(Baseline, week 1 and week 2.)
- Change from baseline in insomnia symptoms assessed by the Insomnia Severity Index (ISI; range: 0-28) at baseline, week 1 and week 2.(Baseline, week 1 and week 2.)
- Change from baseline in suicidal ideation assessed by the Beck Scale for Suicide (BSS-14; range: 0-38) at baseline, week 1 and week 2.(Baseline, week 1 and week 2.)
- Change from baseline in perceived stress assessed by the Perceived Stress Scale-14 (PSS-14; range: 0-56) at baseline, week 1 and week 2.(Baseline, week 1 and week 2.)
- Change from baseline in neurocognitive function using Wsiconsin card sorting test (WCST) at week 2.(Baseline and week 2.)
- Change from baseline in neurocognitive function using Verbal Emotion Perception Test (VEPT) at week 2.(Baseline and week 2.)
- Change from baseline in manic symptoms assessed by the Young Manic Rating Scale(YMRS) at baseline, week 1 and week 2. scales.(Baseline, week 1 and week 2.)
- Changes from metabolites in peripheral blood.(Baseline, week 1 and week 2.)
- Electroencephalogram - delta waves (0.5-4 Hz)(Baseline)
- Electroencephalogram - alpha waves (8-13 Hz)(Baseline)
- Electroencephalogram- gamma waves (above 30 Hz)(Baseline)
- Changes from protein samples in peripheral blood.(Baseline, week 1 and week 2.)
- Changes from methylation in peripheral blood.(Baseline, week 1 and week 2.)
- Electroencephalogram - theta waves (4-8 Hz)(Baseline)
- Change from baseline in psychotic symptoms assessed by the Brief Psychiatric Rating Scale (BPRS) at baseline, week 1 and week 2. scales.(Baseline, week 1 and week 2.)
- Change from baseline in anxious symptoms assessed by the Hamilton anxiely scale (HAMA) at baseline, week 1 and week 2. scales.(Baseline, week 1 and week 2.)
- Change from baseline in anhedonia symptoms assessed by the Snaith-Hamilton Pleasure Scale(SHAPS) at baseline, week 1 and week 2.(Baseline, week 1 and week 2.)
- Change from baseline in anhedonia symptoms assessed by the Temporal Experience of Pleasure Scale (TEPS) at baseline, week 1 and week 2.(Baseline, week 1 and week 2.)