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

NCT07139964 | Completed DMC

• 1 other identifier: DP.04.03/D.XVIII.6.8/ETIK/106/
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Diabetic Foot Ulcer; Vitamin D Deficiency; Wound Healing Disorder

Keywords

Diabetic foot ulcer; Vitamin D3 supplementation

Outcome Measures

Primary Outcomes (1)

• Change in tissue MMP-9/TIMP-1 expression ratio from baseline to Day 28

  Ratio of matrix metalloproteinase-9 (MMP-9) to tissue inhibitor of metalloproteinase-1 (TIMP-1) expression in wound tissue, measured using immunohistochemistry from surgical biopsy samples.

  Baseline (Day 0) and after completion of intervention (Day 28)

Secondary Outcomes (5)

• Change in wound size from baseline to Day 28

  Baseline (Day 0) and Day 28

• Change in serum vitamin D3 concentration from baseline to Day 28

  Baseline (Day 0) and Day 28

• Change in tissue MMP-9 expression from baseline to Day 28

  Baseline (Day 0) and Day 28

• Change in tissue TIMP-1 expression from baseline to Day 28

  Baseline (Day 0) and Day 28

• Correlation between serum vitamin D3 level and wound healing outcomes

  Baseline (Day 0) to Day 28

Study Arms (2)

Experimental: High-dose Vitamin D3

EXPERIMENTAL

Description: Participants receive oral vitamin D3, 10,000 IU daily for 28 days, plus standard care for diabetic foot ulcers. Intervention Name: Vitamin D3 (Cholecalciferol) Type: Dietary Supplement Dosage: 10,000 IU daily Duration: 28 days

Dietary Supplement: Vitamin D3

Placebo Comparator: Placebo

PLACEBO COMPARATOR

Description: Participants receive oral placebo daily for 28 days, plus standard care for diabetic foot ulcers. Intervention Name: Placebo Type: Inactive substance Dosage: Matched placebo daily Duration: 28 days

Other: Placebo

Interventions

Vitamin D3 DIETARY_SUPPLEMENT

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.

Also known as: Cholecalciferol

Experimental: High-dose Vitamin D3

Placebo OTHER

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.

Also known as: Inert capsule

Placebo Comparator: Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of diabetic foot ulcer (DFU) Serum 25-hydroxyvitamin D level \< 30 ng/mL Willingness and ability to provide written informed consent Ability to comply with study procedures and follow-up visits

You may not qualify if:

• Currently undergoing cancer treatment Pregnant or breastfeeding Current use of vitamin D supplementation History of autoimmune disease Chronic kidney disease with estimated GFR \< 30 mL/min/1.73 m² Abnormal liver function tests (AST or ALT ≥ 3× upper normal limit) Ankle-brachial index (ABI) \< 0.4 Presence of osteomyelitis Proven sepsis Allergy to vitamin D3 Amputation prior to randomization Withdrawal of consent during the study

Sponsors & Collaborators

• Universitas Sriwijaya: lead

Study Sites (1)

Dr. Mohammad Hoesin General Hospital

Palembang, South Sumatra, Indonesia

Location

Related Publications (5)

• Shin MH, Lee Y, Kim MK, Lee DH, Chung JH. UV increases skin-derived 1alpha,25-dihydroxyvitamin D3 production, leading to MMP-1 expression by altering the balance of vitamin D and cholesterol synthesis from 7-dehydrocholesterol. J Steroid Biochem Mol Biol. 2019 Dec;195:105449. doi: 10.1016/j.jsbmb.2019.105449. Epub 2019 Aug 27.

  PMID: 31470109 RESULT

• Luanraksa S, Jindatanmanusan P, Boonsiri T, Nimmanon T, Chaovanalikit T, Arnutti P. An MMP/TIMP ratio scoring system as a potential predictive marker of diabetic foot ulcer healing. J Wound Care. 2018 Dec 2;27(12):849-855. doi: 10.12968/jowc.2018.27.12.849.

  PMID: 30557113 RESULT

• Kim SH, Baek MS, Yoon DS, Park JS, Yoon BW, Oh BS, Park J, Kim HJ. Vitamin D Inhibits Expression and Activity of Matrix Metalloproteinase in Human Lung Fibroblasts (HFL-1) Cells. Tuberc Respir Dis (Seoul). 2014 Aug;77(2):73-80. doi: 10.4046/trd.2014.77.2.73. Epub 2014 Aug 29.

  PMID: 25237378 RESULT

• Masood MQ, Khan A, Awan S, Dar F, Naz S, Naureen G, Saghir S, Jabbar A. COMPARISON OF VITAMIN D REPLACEMENT STRATEGIES WITH HIGH-DOSE INTRAMUSCULAR OR ORAL CHOLECALCIFEROL: A PROSPECTIVE INTERVENTION STUDY. Endocr Pract. 2015 Oct;21(10):1125-33. doi: 10.4158/EP15680.OR. Epub 2015 Jul 7.

  PMID: 26151421 RESULT

• Razzaghi R, Pourbagheri H, Momen-Heravi M, Bahmani F, Shadi J, Soleimani Z, Asemi Z. The effects of vitamin D supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial. J Diabetes Complications. 2017 Apr;31(4):766-772. doi: 10.1016/j.jdiacomp.2016.06.017. Epub 2016 Jun 23.

  PMID: 27363929 RESULT

MeSH Terms

Conditions

Diabetic Foot; Vitamin D Deficiency

Interventions

Cholecalciferol

Condition Hierarchy (Ancestors)

Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Study Officials

• Kemas M Dahlan, M.D.

  Consultant Vascular Surgeon, Department of Surgery, Dr. Mohammad Hoesin General Hospital Palembang

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2025
• First Posted: August 24, 2025
• Study Start: July 1, 2024
• Primary Completion: January 31, 2025
• Study Completion: July 31, 2025
• Last Updated: August 24, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

ID (1)