HD-tDCS for Adolescent Bipolar Depression Targeting S1

Jiangsu Province Nanjing Brain Hospital100 enrolled

Overview

This randomized, double-blind, sham-controlled clinical trial aims to evaluate the efficacy and underlying biological mechanisms of HD-tDCS targeting the primary somatosensory cortex in adolescents with bipolar depression. Participants will be randomly assigned to receive either active HD-tDCS or sham stimulation, in addition to routine clinical care. Biological data, including neuroimaging, blood biomarkers, voice and facial features, Photoplethysmography (PPG), Electroencephalography (EEG), and behavioral data, will be collected to explore potential predictors of treatment response.

This study aims to evaluate the efficacy and underlying biological mechanisms of HD-tDCS targeting the primary somatosensory cortex (S1) in adolescents with bipolar depression. Participants will be randomly assigned (1:1) to receive either active HD-tDCS or sham stimulation for 10 consecutive days (twice daily, 20 minutes each session), in addition to standard clinical care. Multimodal assessments will be conducted at baseline, mid-treatment (after 10 sessions), and post-treatment, including clinical symptom scales, neurocognitive evaluations, structural and functional MRI, blood biomarkers (15ml of peripheral blood), as well as digital phenotyping data such as voice, EEG, PPG, sleep, and behavioral metrics. The study also aims to identify objective biomarkers predictive of treatment response and to elucidate the neurobiological mechanisms associated with HD-tDCS applied to the S1 region. All procedures including MRI, tDCS, and assessments are non-invasive and free of charge for participants. The total duration of data collection and follow-up is expected to span approximately two years.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

100

Interventions

Active HD-tDCSDEVICE

HD-tDCS is a non-invasive neuromodulation therapy which has been recognized as a helpful treatment for depression. During each HD-tDCS treatment, the electrode field is generated by a 4\*1 ring montage which is placed over the scalp on the brain region of interest with an electrical current induced to modulate brain activity.

Antipsychotics, mood stabilizers, etc.DRUG

During the HD-tDCS treatment period, all the participants will maintain the stable medication regimen according to clinical practice guidelines.

Sham HD-tDCSDEVICE

Sham HD-tDCS is administered using the same electrode configuration as the active HD-tDCS condition. During each session, the device ramps up current briefly (typically 30 seconds) to mimic the initial sensation of stimulation, then remains off for the remainder of the 20-minute session. This method produces the same tactile perception as active stimulation without delivering a therapeutic dose of current.

Eligibility

Sex: ALLMin age: 12 YearsMax age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Between 12 and 18 years of age; * Participants fulfill the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnostic criteria for bipolar disorder (BD). Participants are assessed by the Structured Clinical Interview for DSM-IV for Axis I Disorders (SCID-I, patients' age ≥18 years old), or the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K- SADS-PL, patients' age\< 18 years old); * A current moderate or severe depressive episode defined by HAMD≥17 and Young Mania Rating Scale (YMRS) \<12; * Participants receive a stable psychotropic medication regimen prior to randomization to the trial and are willing to remain on the stable regimen during the HD-tDCS treatment phase; * Participants and 1 or 2 parents (patients' age\< 18 years old) provide informed consent after the detailed description of the study. Exclusion Criteria: * Prior rTMS or tDCS or electroconvulsive therapy (ECT) treatment 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, metal implants); * Contraindications to tDCS (e.g., metal in head, history of seizure, EEG test suggesting high risk of seizure, known brain lesion); * Current drug/alcohol abuse or dependence; * Pregnant or lactating female.

Outcomes

Primary Outcomes

Change from baseline in depressive symptoms assessed by the 17-item Hamilton Depression Rating Scale (HAMD-17) at 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.

Time frame: Baseline and after 2 weeks.

Secondary Outcomes

Change from baseline in depressive symptoms assessed by HAMD-17 after week 1.

Time frame: Baseline and after 1 week.

Change in anxiety symptoms assessed by Hamilton Anxiety Rating Scale (HAMA) after week 1 and after week 2.

The HAMA consists of 14 items designed to assess the severity of a patient's anxiety. Each item is rated on a scale of 0 (not present) to 4 (severe), with a total score ranging from 0 to 56. Higher scores indicate greater anxiety. Change in total score from baseline will be calculated.

Time frame: Baseline, after 1week and after 2 weeks.

Change from baseline in the Clinical Global Impression-Severity scale (CGI-S) after week 1 and after week 2.

The CGI-S is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. A rating of 1 is considered normal, or with the least severe symptoms, a rating of 7 is extremely ill, or the worst symptoms.

Time frame: Baseline and after 1 week and after 2 weeks.

Change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) after 1 week and after 2 week.

MADRS is a clinician-rated scale used to assess depressive symptom severity and detect changes due to antidepressant treatment. The scale consists of 10 items, each of which is rated from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms). The total score of MADRS ranges from 0 to 60, with higher score indicating more severe depression.

Time frame: Baseline, after 1 week and after 2 weeks.

Change in brain functional connectivity measured by resting-state functional MRI

Resting-state functional magnetic resonance imaging (rs-fMRI) will be used to assess changes in the connectivity of the primary S1 and associated networks.

Time frame: Baseline, after 1 week and after 2 weeks.

Change in Cytokines (reported in pg/mL)

Peripheral blood biomarkers will be measured to evaluate inflammatory and immune responses to HD-tDCS treatment. Interferon-α (IFN-α) Interferon-γ (IFN-γ) Interleukin-1β (IL-1β) Interleukin-2 (IL-2) Interleukin-4 (IL-4) Interleukin-5 (IL-5) Interleukin-6 (IL-6) Interleukin-8 (IL-8) Interleukin-10 (IL-10) Interleukin-17 (IL-17) Tumor necrosis factor-alpha (TNF-α)

Time frame: Baseline, after 1 week, and after 2 weeks.

Change in Immune-inflammatory ratios (unitless)

Platelet-to-lymphocyte ratio (PLR) Neutrophil-to-lymphocyte ratio (NLR) Monocyte-to-HDL cholesterol ratio (MHR) These biomarkers are selected to reflect systemic inflammatory activity and immune status.

Time frame: Baseline, after 1 week, and after 2 weeks.

Adverse events and tolerability of HD-tDCS

Adverse events related to HD-tDCS will be monitored throughout the treatment period. Participants will be evaluated for scalp irritation, headache, dizziness, fatigue, or other discomforts after each session. Severity and frequency will be recorded using a standardized adverse event form.

Time frame: Baseline, after 1 week and after 2 weeks