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

Official title

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

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.

Interventions

• Behavioral Virtual Reality Mindfulness-Based Cognitive Therapy (Active VR-MBCT)
  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.
• Device Active transcranial Direct Current Stimulation (Active tDCS)
  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.
• Behavioral Sham Virtual Reality Mindfulness Program (Sham VR-MBCT)
  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.
• Device Sham transcranial Direct Current Stimulation (Sham tDCS)
  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.

Primary outcome measures

• Change in Patient Health Questionnaire-9 (PHQ-9) Score [Time frame: Baseline , Week 1, Week 2, Week 3, Week 4, Week 8, Week 28]
• Hamilton Depression Rating Scale-24 (HDRS-24) Score [Time frame: Baseline , Week 1, Week 2, Week 3, Week 4, Week 8, Week 28]

Secondary outcome measures (11)

• Treatment Retention Rate [Time frame: Week 4]
• Intervention Adherence Rate [Time frame: Week 4]
• Change in HAMA Score [Time frame: Baseline, Week 4, Week 8, Week 28]
• Change in Snaith-Hamilton Pleasure Scale (SHAPS) Score [Time frame: Baseline, Week 4, Week 8, Week 28]
• Change in Five Facet Mindfulness Questionnaire (FFMQ) Score [Time frame: Baseline, Week 4, Week 8, Week 28]
• Change in Pittsburgh Sleep Quality Index (PSQI) Score [Time frame: Baseline, Week 4, Week 8, Week 28]
• Change in Patient Health Questionnaire-15 (PHQ-15) Score [Time frame: Baseline, Week 4, Week 8, Week 28]
• Change in modified Rankin Scale (mRS) Score [Time frame: Baseline, Week 4, Week 8, Week 28]
• Change in 36-Item Short Form Health Survey (SF-36) Score [Time frame: Baseline, Week 4, Week 8, Week 28]
• Change in Hospital Anxiety and Depression Scale (HADS) Score [Time frame: Baseline, Week 4, Week 8, Week 28]
• Change in resting-state functional connectivity (fMRI) [Time frame: Baseline, Week 4, Week 28]

Eligibility criteria

Inclusion criteria

• Aged 18 to 65 years (inclusive).
• Stroke onset ≥ 4 weeks, with stable condition and an NIHSS score ≤ 15.
• Right-handed.
• Patient must be in a depressive episode, defined by a PHQ-9 score ≥ 5 and confirmed by a HDRS-24 score ≥ 8.
• Has not used any antidepressants before the enrollment.
• No contraindications to tDCS (e.g., metal plates in the head, brain implants, aneurysm clips, cochlear implants, cardiac pacemakers, etc.).
• Has not received systematic psychotherapy (such as MBCT, mindfulness training, or cognitive behavioral therapy) for the current or previous depressive episodes.
• Has more than 8 years of formal education.
• Has not received tDCS or other transcranial electrical stimulation treatment for the current or previous depressive episodes.
• Is able to cooperate with multimodal MRI data collection and follow-up assessments, and can understand and comply with the study requirements.

Exclusion criteria

• 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).
• 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.
• Baseline Mini-Mental State Examination (MMSE) score ≤ 24.
• Presence of suicidal ideation or plan within 4 weeks prior to baseline.
• Depressive symptoms are better explained by another clinical condition (e.g., hypothyroidism, anemia, congestive heart failure) or other mental disorders.
• Presence of severe, unstable cardiovascular, hepatic, renal, hematological, endocrine diseases, or malignancies.
• 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.
• Poorly controlled hypertension (sitting systolic blood pressure (SBP) ≥ 180 mmHg or sitting diastolic blood pressure (DBP) ≥ 110 mmHg at screening or baseline).
• 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.
• Pregnant, lactating, or planning pregnancy.
• Significant visual or hearing impairment that prevents participation in interventions or assessments.
• Received brain stimulation therapy (e.g., ECT, mECT, TMS, rTMS, deep brain stimulation, vagus nerve stimulation) within 3 months prior to baseline.
• Participation in another clinical trial within 1 month prior to baseline (excluding screening failures).
• Any other condition deemed by the investigator as unsuitable for participation in the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07422740 · 2025-0626

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗