Clinical trial NCT05498441: Personalized High-Definition Transcranial Direct Current Stimulation (HD-tDCS) Treatment for Major Depressive Episode
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Major Depressive Episode
Keywords: High-Definition Transcranial Direct Current Stimulation
Major Depressive Episode
Magnetic Resonance Imaging
Adolescent
Lead sponsor: Jiangsu Province Nanjing Brain Hospital
Sponsor class: OTHER
First posted: 2022-08-12
Enrollment: 120
Sex: ALL
Minimum age (years): 13
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Change from baseline in depressive symptoms assessed by Hamilton depression rating scale 17 items (HAMD-17) at week 1 and week 2.
timeFrame: Baseline, week 1 and week 2
measure: Change from baseline in neurocognitive function using Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) test at week 2.
timeFrame: Baseline and week 2.
measure: Change from baseline in resting-state magnetic resonance imaging (MRI) , diffusion tensor imaging (DTI) and structural (T1-weighted) imaging at weeks 1 and 2.
timeFrame: Baseline, week 1 and week 2.
Secondary outcomes:
measure: Change from baseline in the Clinical Global Impression-Severity scale (CGI-S) at week 1 and week 2.
timeFrame: Baseline, week 1 and week 2.
measure: Change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) at week 1 and week 2.
timeFrame: Baseline, week 1 and week 2.
measure: 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.
timeFrame: Baseline, week 1 and week 2.
measure: 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.
timeFrame: Baseline, week 1 and week 2.
measure: Change from baseline in insomnia symptoms assessed by the Insomnia Severity Index (ISI; range: 0-28) at baseline, week 1 and week 2.
timeFrame: Baseline, week 1 and week 2.
measure: 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.
timeFrame: Baseline, week 1 and week 2.
measure: 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.
timeFrame: Baseline, week 1 and week 2.
measure: Change from baseline in neurocognitive function using Wsiconsin card sorting test (WCST) at week 2.
timeFrame: Baseline and week 2.
measure: Change from baseline in neurocognitive function using Verbal Emotion Perception Test (VEPT) at week 2.
timeFrame: Baseline and week 2.
measure: Change from baseline in neurocognitive function using Facial Emotion Perception Test (FEPT) at week 2.
timeFrame: Baseline and week 2.
measure: Change from baseline in acoustic features.
timeFrame: Baseline, week 1 and week 2.
measure: Change from baseline in manic symptoms assessed by the Young Manic Rating Scale(YMRS) at baseline, week 1 and week 2. scales.
timeFrame: Baseline, week 1 and week 2.
measure: Changes from metabolites in peripheral blood.
timeFrame: Baseline, week 1 and week 2.
measure: Changes from protein samples in peripheral blood.
timeFrame: Baseline, week 1 and week 2.
measure: Changes from methylation in peripheral blood.
timeFrame: Baseline, week 1 and week 2.
measure: Electroencephalogram - delta waves (0.5-4 Hz)
timeFrame: Baseline
measure: Electroencephalogram - theta waves (4-8 Hz)
timeFrame: Baseline
measure: Electroencephalogram - alpha waves (8-13 Hz)
timeFrame: Baseline
measure: Electroencephalogram - Beta Waves (13-30 Hz)
timeFrame: Baseline
measure: Electroencephalogram- gamma waves (above 30 Hz)
timeFrame: Baseline
measure: Change from baseline in psychotic symptoms assessed by the Brief Psychiatric Rating Scale (BPRS) at baseline, week 1 and week 2. scales.
timeFrame: Baseline, week 1 and week 2.
measure: Change from baseline in anxious symptoms assessed by the Hamilton anxiely scale (HAMA) at baseline, week 1 and week 2. scales.
timeFrame: Baseline, week 1 and week 2.
measure: Change from baseline in anhedonia symptoms assessed by the Snaith-Hamilton Pleasure Scale(SHAPS) at baseline, week 1 and week 2.
timeFrame: Baseline, week 1 and week 2.
measure: Change from baseline in anhedonia symptoms assessed by the Temporal Experience of Pleasure Scale (TEPS) at baseline, week 1 and week 2.
timeFrame: Baseline, week 1 and week 2.
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Affiliated Nanjing Brain Hospital, Nanjing Medical University
state: Jiangsu
Study officials:
affiliation: Affiliated Nanjing Brain Hospital, Nanjing Medical University
name: Fei Wang
role: STUDY_CHAIR
References: