Intervention Study of Virtual Reality-Based Mindfulness-Based Cognitive Therapy (VR-MBCT) Combined With Adaptive tDCS Modulation for Post-Stroke Depression

N/ANot Yet RecruitingNCT07422740

Second Affiliated Hospital, Zhejiang University, School of Medicine120 enrolled

Overview

This study investigates whether combining virtual reality mindfulness-based cognitive therapy (VR-MBCT) with transcranial direct current stimulation (tDCS) can effectively treat depression occurring after a stroke (post-stroke depression, PSD). The goal is to determine if this combined approach is more beneficial than either treatment alone or standard care in alleviating depressive symptoms. The study will enroll adults aged 18-65 who have experienced a stroke within the past week, are medically stable, and exhibit moderate to severe depression symptoms. Participants must be right-handed and able to undergo MRI scans and study assessments. Individuals with certain neurological or psychiatric conditions, other major health issues, or specific contraindications for tDCS will not be eligible. Procedures: This is a randomized controlled trial lasting approximately 28 weeks, divided into two phases. In the first phase (8 weeks), participants are randomly assigned to one of four groups: Group 1: Receives sham (placebo) versions of both VR-MBCT and tDCS plus standard medication. Group 2: Receives active tDCS and sham VR-MBCT plus standard medication. Group 3: Receives active VR-MBCT and sham tDCS plus standard medication. Group 4: Receives both active VR-MBCT and active tDCS plus standard medication. Treatments are administered 5-6 times per week for 4 weeks, followed by a 4-week blinded follow-up.The primary outcome is the change in depression scores (HDRS-24、PHQ-9) from baseline to 8 weeks. Secondary outcomes include rates of clinical response, remission, relapse, treatment acceptability, and changes in anxiety, sleep quality, and daily functioning.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

120

Conditions

Interventions

Virtual Reality Mindfulness-Based Cognitive Therapy (Active VR-MBCT)BEHAVIORAL

Participants will receive a structured Virtual Reality Mindfulness-Based Cognitive Therapy program specifically designed for post-stroke depression. The intervention aims to improve emotional regulation and cognitive function through immersive mindfulness exercises. It is administered 5 sessions per week for 4 weeks, with each session lasting approximately 30 minutes. The content includes breathing techniques, and mindfulness practices within a virtual reality environment.

Active transcranial Direct Current Stimulation (Active tDCS)DEVICE

Participants will receive active transcranial Direct Current Stimulation using a programmable stimulator. The anodal electrode will be placed over the left dorsolateral prefrontal cortex (DLPFC) and the cathodal electrode over the right supraorbital area. Stimulation will be administered at 2.0 mA for 30 minutes per session, once daily, for 4 weeks. The device delivers a constant, low-intensity electrical current intended to modulate cortical excitability.

Sham Virtual Reality Mindfulness Program (Sham VR-MBCT)BEHAVIORAL

Participants in the control groups will experience a sham VR program. It uses the same virtual reality hardware but presents neutral, non-therapeutic content (e.g., nature scenes without guided mindfulness instruction) accompanied by audio containing general psychoeducation about stroke recovery and white noise. The frequency and duration (5 sessions/week, 30 minutes/session for 4 weeks) match the Active VR-MBCT intervention to control for non-specific effects like attention and device use.

Sham transcranial Direct Current Stimulation (Sham tDCS)DEVICE

The sham tDCS intervention uses the same device and setup as the Active tDCS arm to maintain blinding. The device will deliver a brief initial current ramp (e.g., 30 seconds) to mimic the sensory skin sensation (tingling/itching) of active stimulation, but will then automatically shut off or deliver only a negligible current for the remainder of the 30-minute session. This procedure ensures participants cannot distinguish it from the active stimulation based on initial sensation alone.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Aged 18 to 65 years (inclusive). 2. Stroke onset ≥ 4 weeks, with stable condition and an NIHSS score ≤ 15. 3. Right-handed. 4. Patient must be in a depressive episode, defined by a PHQ-9 score ≥ 5 and confirmed by a HDRS-24 score ≥ 8. 5. Has not used any antidepressants before the enrollment. 6. No contraindications to tDCS (e.g., metal plates in the head, brain implants, aneurysm clips, cochlear implants, cardiac pacemakers, etc.). 7. Has not received systematic psychotherapy (such as MBCT, mindfulness training, or cognitive behavioral therapy) for the current or previous depressive episodes. 8. Has more than 8 years of formal education. 9. Has not received tDCS or other transcranial electrical stimulation treatment for the current or previous depressive episodes. 10. Is able to cooperate with multimodal MRI data collection and follow-up assessments, and can understand and comply with the study requirements. Exclusion Criteria: 1. History of treatment-resistant depression, defined as failure to respond to at least two different antidepressant medications of adequate dosage and duration (at least 8 weeks at the maximum recommended therapeutic dose). 2. Other psychiatric diagnoses (e.g., intellectual disability, schizophrenia, affective psychosis, bipolar disorder, obsessive-compulsive disorder, attention deficit hyperactivity disorder, eating disorders, personality disorders, substance use disorders, post-traumatic stress disorder, panic disorder, or social phobia). Co-morbid anxiety disorder is acceptable. 3. Baseline Mini-Mental State Examination (MMSE) score ≤ 24. 4. Presence of suicidal ideation or plan within 4 weeks prior to baseline. 5. Depressive symptoms are better explained by another clinical condition (e.g., hypothyroidism, anemia, congestive heart failure) or other mental disorders. 6. Presence of severe, unstable cardiovascular, hepatic, renal, hematological, endocrine diseases, or malignancies. 7. Laboratory tests indicating significant impairment: total bilirubin (TBIL) \> 1.5 times the upper limit of normal (ULN); alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 3 times ULN; glomerular filtration rate (GFR) ≤ 70 mL/min; or thyroid-stimulating hormone (TSH) outside the normal range. 8. Poorly controlled hypertension (sitting systolic blood pressure (SBP) ≥ 180 mmHg or sitting diastolic blood pressure (DBP) ≥ 110 mmHg at screening or baseline). 9. Epilepsy and/or other neurological diseases (e.g., dementia, traumatic brain injury, Parkinson's disease, Huntington's disease, multiple sclerosis), or any neurological condition leading to increased intracranial pressure, brain damage, or increased risk of seizures. 10. Pregnant, lactating, or planning pregnancy. 11. Significant visual or hearing impairment that prevents participation in interventions or assessments. 12. Received brain stimulation therapy (e.g., ECT, mECT, TMS, rTMS, deep brain stimulation, vagus nerve stimulation) within 3 months prior to baseline. 13. Participation in another clinical trial within 1 month prior to baseline (excluding screening failures). 14. Any other condition deemed by the investigator as unsuitable for participation in the study.

Outcomes

Primary Outcomes

Change in Patient Health Questionnaire-9 (PHQ-9) Score

The Patient Health Questionnaire-9 (PHQ-9) is a 9-item self-report scale for assessing depressive symptom severity based on frequency over the past two weeks. Total scores range from 0 to 27, with higher scores indicating greater depression severity. Change in total score from Baseline to Week 28 serves as a primary efficacy measure.

Time frame: Baseline , Week 1, Week 2, Week 3, Week 4, Week 8, Week 28

Hamilton Depression Rating Scale-24 (HDRS-24) Score

The Hamilton Depression Rating Scale-24 item (HDRS-24) is a clinician-administered scale for assessing depressive symptom severity. Total scores range from 0 to 74, with higher scores indicating greater depression severity. Change in total score from Baseline to Week 28 serves as a primary efficacy measure.

Time frame: Baseline , Week 1, Week 2, Week 3, Week 4, Week 8, Week 28

Secondary Outcomes

Treatment Retention Rate

The proportion of participants who remain in the study and complete the assigned intervention by the end of Week 4. This will be calculated separately for each group as: (Number of participants randomized - Number of participants who withdrew prior to Week 4) / Number of participants randomized × 100%.

Time frame: Week 4

Intervention Adherence Rate

The degree to which participants complete the prescribed intervention sessions. It will be calculated as the total minutes of intervention sessions actually attended (or completed in the VR system) divided by the total minutes of intervention sessions prescribed by the protocol up to Week 4, expressed as a percentage. Adherence data will be objectively recorded by the VR system.

Time frame: Week 4

Change in HAMA Score

The Hamilton Anxiety Rating Scale (HAMA) is a clinician-administered scale used to rate the severity of anxiety symptoms. Total scores range from 0 to 56, with higher scores indicating greater severity of anxiety. The change from baseline to post-intervention will be calculated