Efficacy of Vitamin D in Post-Stroke Cognitive Impairment

Background and Rationale:

Post-stroke cognitive impairment (PSCI) is a prevalent complication that severely impacts patient rehabilitation and quality of life. Recent studies suggest that Vitamin D deficiency is highly prevalent in stroke patients and is closely associated with neuroinflammation and cognitive decline. However, high-quality clinical evidence regarding the efficacy of Vitamin D supplementation in PSCI and its underlying immunological mechanisms remains limited. This study aims to bridge this gap by providing clinical and mechanistic evidence.

Study Design and Participants:

This is a prospective, randomized, double-blind, placebo-controlled clinical trial. Eligible participants are adult patients diagnosed with acute ischemic stroke complicated by cognitive impairment within 7 days of onset. Patients with severe hepatic or renal dysfunction, or those already receiving high-dose Vitamin D therapy, will be excluded.

Intervention:

Eligible participants will be randomly assigned (1:1) to either the intervention group or the control group.

Intervention Group: Will receive oral Vitamin D2 capsules (5000 IU/day) for 6 months.

Control Group: Will receive identical placebo capsules for 6 months. Both patients and investigators will be blinded to the group assignments.

Outcome Assessments:

Primary Outcome: Changes in cognitive function from baseline to 6 months, assessed using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE).

Secondary Outcomes: Changes in serum immune-inflammatory markers, including IL-6, TNF-α, IL-10, and the proportion of regulatory T cells (Tregs), measured via ELISA and flow cytometry at baseline and 6 months.

Sample Size and Statistical Analysis:

Based on a power calculation considering a 20% dropout rate, a total of 300 participants will be enrolled. All statistical analyses will be performed using SPSS software. Continuous variables will be compared using t-tests or Mann-Whitney U tests, while categorical variables will be analyzed using Chi-square tests. A p-value < 0.05 will be considered statistically significant.

Inclusion criteria

• Age: Aged 18 to 80 years (inclusive).
• Diagnosis: First-ever ischemic or hemorrhagic stroke, confirmed by brain CT or MRI within 1 week of onset.
• Time Window: Post-stroke duration between 3 months and 24 months.
• Cognitive Status: Presence of cognitive impairment, defined as a Montreal Cognitive Assessment (MoCA) score < 26 (or your specific cutoff) at screening.
• Stability: Clinically stable condition, without recurrent stroke or transient ischemic attack (TIA) in the past 3 months.
• Consent: Ability to provide written informed consent by the participant or their legal representative.
• Compliance: Willingness and ability to comply with the study protocol and follow-up visits.

Exclusion criteria

• Severe Disability: Pre-morbid or current modified Rankin Scale (mRS) score > 3.
• Other CNS Diseases: Presence of other neurological diseases that could cause cognitive decline (e.g., Parkinson's disease, epilepsy, brain tumor, or severe traumatic brain injury).
• Psychiatric Disorders: History of major psychiatric disorders (e.g., schizophrenia, severe depression) that may interfere with cognitive testing.
• Vitamin D Status: Known history of hypercalcemia, hypercalciuria, or sarcoidosis; or current use of vitamin D supplements (>800 IU/day) or calcium supplements within the past 3 months.
• Severe Comorbidities: Severe dysfunction of heart, liver, or kidney (e.g., ALT/AST > 3x ULN, eGFR < 30 mL/min/1.73m²).
• Life Expectancy: Life expectancy less than 6 months due to malignant tumors or other terminal illnesses.
• Allergy: Known allergy or hypersensitivity to vitamin D or any components of the study formulation.
• Participation: Participation in another interventional clinical trial within the past 30 days.