NCT07139964

High-Dose Vitamin D3 for Diabetic Foot Ulcer Healing: Randomized Controlled Trial

Effectiveness of High-Dose Vitamin D3 in Improving Diabetic Foot Ulcer Healing by Reducing the MMP-9 to TIMP-1 Ratio: Randomized Double-Blind Placebo-Controlled Trial

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 24 (actual)
• Sponsor: Universitas Sriwijaya · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This randomized, double-blind, placebo-controlled clinical trial aims to evaluate the effectiveness of high-dose vitamin D3 supplementation in improving diabetic foot ulcer (DFU) healing. DFUs are common, serious complications of diabetes, often associated with delayed wound healing due to persistent inflammation, impaired angiogenesis, and imbalances between matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor (TIMP-1). Vitamin D deficiency is prevalent among DFU patients and is linked to impaired fibroblast function, poor angiogenesis, and increased inflammation. Participants with DFUs and serum vitamin D levels \<30 ng/mL will be randomized to receive either 10,000 IU oral vitamin D3 daily or placebo for 28 days, in addition to standard DFU care. Primary outcomes include changes in tissue MMP-9/TIMP-1 expression ratio and wound healing progression. The study will provide evidence on whether high-dose vitamin D3 can serve as a safe, effective adjunctive therapy in DFU management.

Detailed description

Diabetic foot ulcers are a prevalent and serious complication of uncontrolled diabetes, with a significant proportion leading to infection, amputation, and mortality. Delayed wound healing in DFUs is often driven by prolonged inflammation, persistent infection, impaired angiogenesis, and an imbalance between extracellular matrix (ECM) degradation by MMP-9 and inhibition by TIMP-1. Elevated MMP-9 levels disrupt keratinocyte migration, collagen deposition, and epithelial regeneration, while reduced TIMP-1 further compromises healing. Vitamin D plays a regulatory role in immune modulation, inflammation control, fibroblast activity, and angiogenesis. Observational and interventional studies have shown that vitamin D deficiency is common in DFU patients and is associated with slower healing. Supplementation has been linked to improved wound healing, reduced inflammatory markers, and better microcirculation. Vitamin D may also modulate MMP-9 and TIMP-1 expression, thereby restoring ECM balance. This study is a double-blind, placebo-controlled, randomized controlled trial conducted at Dr. Mohammad Hoesin General Hospital, Palembang. Eligible participants are adults with DFUs, low serum vitamin D (\<30 ng/mL), and no exclusion criteria such as advanced kidney disease, severe liver disease, osteomyelitis, or sepsis. Participants will be randomized into two groups: Intervention group: Oral vitamin D3, 10,000 IU daily for 28 days Control group: Placebo daily for 28 days Both groups will receive standard DFU care. Compliance will be monitored with the MMAS-8 scale. Primary outcomes are changes in tissue MMP-9 and TIMP-1 expression (assessed by immunohistochemistry) and wound healing parameters. Secondary outcomes include changes in serum vitamin D levels and correlation between vitamin D status and wound healing outcomes. The study aims to determine whether high-dose vitamin D3 supplementation reduces the MMP-9/TIMP-1 ratio and accelerates wound healing, potentially supporting its use as a standard adjunctive therapy for DFUs.

Conditions

• Diabetic Foot Ulcer
• Vitamin D Deficiency
• Wound Healing Disorder

Interventions

Type	Name	Description
DIETARY_SUPPLEMENT	Vitamin D3	Participants receive oral vitamin D3 (cholecalciferol) 10,000 IU daily for 28 consecutive days, in addition to standard diabetic foot ulcer care according to hospital protocols. Vitamin D3 is provided in identical-appearing capsules. Compliance is monitored using the MMAS-8 adherence scale.
OTHER	Placebo	Participants receive an oral placebo capsule daily for 28 consecutive days, in addition to standard diabetic foot ulcer care according to hospital protocols. The placebo is identical in appearance to the vitamin D3 capsule. Compliance is monitored using the MMAS-8 adherence scale.

Timeline

• Start date: 2024-07-01
• Primary completion: 2025-01-31
• Completion: 2025-07-31
• First posted: 2025-08-24
• Last updated: 2025-08-24

Locations

1 site across 1 country: Indonesia