Vitamin D3 for Moderate to Mild Traumatic Brain Injury: A Randomized Trial on Inflammation and Recovery (VIMOT)

Traumatic brain injury (TBI) is a leading cause of death and disability globally, with the majority of cases occurring in low- and middle-income countries (LMICs). Secondary brain injury, driven by inflammation, oxidative stress, and neurovascular disruption, is a major determinant of long-term disability. Despite this burden, there are no approved pharmacological therapies targeting the secondary injury cascade. Vitamin D₃ (cholecalciferol), a fat-soluble secosteroid hormone precursor, has immunomodulatory and neuroprotective properties, including suppression of pro-inflammatory cytokines (e.g., TNF-α, IL-6), enhancement of antioxidant defenses, and stabilization of the blood-brain barrier. However, its therapeutic potential in TBI has not been evaluated in randomized trials in LMICs.

This Phase II, four-arm, randomized, quadruple-blinded, placebo-controlled trial will evaluate the efficacy and safety of vitamin D₃ supplementation in adults (18-65 years) with mild-to-moderate TBI. A total of 240 participants will be stratified by vitamin D status at baseline and allocated into one of four groups:

Group A (Deficient + High-Dose D₃): 50,000 IU loading dose on day 1, followed by 4,000 IU daily for 3 weeks.

Group B (Deficient + Standard-Dose D₃): 2,000 IU daily for 3 weeks.

Group C (Sufficient + Standard-Dose D₃): 2,000 IU daily for 3 weeks.

Group D (Sufficient + Placebo): placebo daily for 3 weeks.

The intervention period is 3 weeks, with follow-up to 24 weeks. Randomization will use stratified block design (age, sex, GCS), and blinding will apply to participants, care providers, investigators, and outcome assessors.

Primary endpoints are changes in inflammatory biomarkers (CRP, ESR, SIRI, SII, PLR, NLR) and functional outcomes measured by the Glasgow Outcome Scale-Extended (GOS-E) and Modified Rankin Scale (mRS). Secondary endpoints include all-cause mortality at 28 days and 24 weeks, hospital length of stay, adverse events (e.g., hypercalcemia), and cost-effectiveness expressed as incremental cost-effectiveness ratios (ICERs) per DALY and QALY averted.

Safety monitoring will include weekly serum calcium and renal function tests during supplementation, adverse event documentation, and oversight by an independent Data Safety Monitoring Board (DSMB). The study will be conducted under Good Clinical Practice (GCP) standards, with regulatory approval and institutional ethics board approval.

This trial is designed to generate context-specific, clinically actionable evidence on whether vitamin D₃ supplementation improves recovery following TBI. If effective, the intervention is highly scalable given its low cost, wide availability, and favorable safety profile, with potential integration into national TBI management guidelines in LMICs.

• Change in inflammatory biomarkers (ESR, SIRI, SII, PLR, NLR) [Срок оценки: 4 weeks]
• Neurological functional recovery assessed by Glasgow Outcome Scale-Extended (GOS-E) [Срок оценки: Week 4, Week 12, and Week 24]
• Neurological functional recovery assessed by Modified Rankin Scale (mRS) [Срок оценки: Baseline, Week 4, Week 12, and Week 24]