High-Definition Transcranial Direct Current Stimulation (HD-tDCS) Targeting the Primary Somatosensory Cortex for Bipolar Depression in Adolescents: A Randomized Double-Blind Controlled Trial
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 100
- Locations
- 1
- Primary Endpoint
- Change from baseline in depressive symptoms assessed by the 17-item Hamilton Depression Rating Scale (HAMD-17) at Week 2.
Study Overview
Brief Summary
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.
Detailed Description
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Outcomes Assessor)
Eligibility Criteria
- Ages
- 12 Years to 18 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
Active HD-tDCS Targeting Right S1
Participants in this arm will receive active HD-tDCS targeting the right S1. Anodal stimulation will be delivered at the C4 position according to the international 10-20 EEG system, with cathodes placed at FC4, C6, C2, and CP4. The current intensity is set at 2.0 mA for 20 minutes per session, administered twice daily for 10 days (total of 20 sessions). Participants received stable pharmacological treatment during the intervention period.
Intervention: Active HD-tDCS (Device)
Active HD-tDCS Targeting Right S1
Participants in this arm will receive active HD-tDCS targeting the right S1. Anodal stimulation will be delivered at the C4 position according to the international 10-20 EEG system, with cathodes placed at FC4, C6, C2, and CP4. The current intensity is set at 2.0 mA for 20 minutes per session, administered twice daily for 10 days (total of 20 sessions). Participants received stable pharmacological treatment during the intervention period.
Intervention: Antipsychotics, mood stabilizers, etc. (Drug)
Sham Stimulation at Right S1
Participants in this arm will receive sham HD-tDCS using the same electrode configuration as the active group (anode at C4; cathodes at FC4, C6, C2, and CP4), but without delivering effective current after the initial ramp-up. The sham stimulation mimics the sensation of real stimulation without physiological effects. Sessions will be delivered twice daily for 10 days (total of 20 sessions). Participants received stable pharmacological treatment during the intervention period.
Intervention: Antipsychotics, mood stabilizers, etc. (Drug)
Sham Stimulation at Right S1
Participants in this arm will receive sham HD-tDCS using the same electrode configuration as the active group (anode at C4; cathodes at FC4, C6, C2, and CP4), but without delivering effective current after the initial ramp-up. The sham stimulation mimics the sensation of real stimulation without physiological effects. Sessions will be delivered twice daily for 10 days (total of 20 sessions). Participants received stable pharmacological treatment during the intervention period.
Intervention: Sham HD-tDCS (Device)
Outcomes
Primary Outcomes
Change from baseline in depressive symptoms assessed by the 17-item Hamilton Depression Rating Scale (HAMD-17) at Week 2.
Time Frame: Baseline and after 2 weeks.
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.
Secondary Outcomes
- Change from baseline in depressive symptoms assessed by HAMD-17 after week 1.(Baseline and after 1 week.)
- Change in anxiety symptoms assessed by Hamilton Anxiety Rating Scale (HAMA) after week 1 and after week 2.(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.(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.(Baseline, after 1 week and after 2 weeks.)
- Change in Cytokines (reported in pg/mL)(Baseline, after 1 week, and after 2 weeks.)
- Change in Immune-inflammatory ratios (unitless)(Baseline, after 1 week, and after 2 weeks.)
- Change in brain functional connectivity measured by resting-state functional MRI(Baseline, after 1 week and after 2 weeks.)
- Adverse events and tolerability of HD-tDCS(Baseline, after 1 week and after 2 weeks)
Investigators
Fei Wang
Professor
Jiangsu Province Nanjing Brain Hospital