PRHDTDCSTMDE: Personalized High-Definition Transcranial Direct Current Stimulation (HD-tDCS) Treatment for Major Depressive Episode

Sponsor

Jiangsu Province Nanjing Brain Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05498441

Collaborator

(none)

120

Enrollment

Location

Arms

12.9

Anticipated Duration (Months)

9.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Episode	Device: High-Definition Transcranial Direct Current Stimulation (HD-tDCS) Drug: Quetiapine, lithium and divalproate	N/A

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 double-blind 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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, Double-blind, Controlled Study

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Sep 30, 2023

Anticipated Study Completion Date :

Sep 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Device: High-Definition Transcranial Direct Current Stimulation (HD-tDCS) High-Definition Transcranial Direct Current Stimulation (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 41 ring montage which is placed over the scalp on the brain region of interest with an electrical current induced to modulate brain activity. Drug: Quetiapine, lithium and divalproate* During the HD-tDCS treatment period, all the participants will maintain the stable medication regimen including first-line pharmacological therapy (quetiapine, lithium and divalproate) according to clinical practice guidelines.
Active Comparator: 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.	Device: High-Definition Transcranial Direct Current Stimulation (HD-tDCS) High-Definition Transcranial Direct Current Stimulation (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 41 ring montage which is placed over the scalp on the brain region of interest with an electrical current induced to modulate brain activity. Drug: Quetiapine, lithium and divalproate* During the HD-tDCS treatment period, all the participants will maintain the stable medication regimen including first-line pharmacological therapy (quetiapine, lithium and divalproate) according to clinical practice guidelines.

Arm

Intervention/Treatment

Experimental: 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.

Device: High-Definition Transcranial Direct Current Stimulation (HD-tDCS)

High-Definition Transcranial Direct Current Stimulation (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.

Drug: Quetiapine, lithium and divalproate

During the HD-tDCS treatment period, all the participants will maintain the stable medication regimen including first-line pharmacological therapy (quetiapine, lithium and divalproate) according to clinical practice guidelines.

Active Comparator: 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.

Device: High-Definition Transcranial Direct Current Stimulation (HD-tDCS)

Drug: Quetiapine, lithium and divalproate

Outcome Measures

Primary Outcome Measures

Change from baseline in depressive symptoms assessed by Hamilton depression rating scale 17 items (HAMD-17) at week 1 and week 2. [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. [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 the amplitude of low-frequency fluctuation (ALFF) values measured by resting-state functional magnetic resonance imaging (fMRI) at week 1 and week 2. [Baseline, week 1 and week 2.]
Participants will undergo fMRI 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). ALFF is a fMRI indicator that reflects the spontaneous neural activity. After data acquisition, whole-brain voxel-wise analysis of ALFF values will be performed to detect the change from baseline in brain functional activity at week 1 and week 2.

Secondary Outcome Measures

Change from baseline in the Clinical Global Impression-Severity scale (CGI-S) at week 1 and week 2. [Baseline, week 1 and 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.
Change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) at week 1 and week 2. [Baseline, week 1 and week 2.]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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,MADRS≥30 and YMRS<12;
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;
Participants and 1 or 2 parents provide informed consent 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.