ACTRN12613000418774.

Trial name or title	Effects of Galvus (vildagliptin) on markers of inflammation in diabetic foot ulcer: a prospective, randomized, double‐blind, placebo‐controlled pilot study
Methods	The objective of this trial is to study the effects of vildagliptin therapy on inflammatory markers in subjects with diabetic foot ulcer. The study plans to prospectively enrol 50 patients with proven diabetic foot ulcer and randomize them in a 1:1, ratio to vildagliptin + metformin or placebo + metformin. The study expects to show an improvement (defined as > 20% serum IL‐6 reduction between the baseline and 3‐month assessment) that comprise the primary end point in at least 50% of the patients randomized to vildagliptin and metformin therapy and in < 10% of the patients randomized to metformin and placebo therapy. The proposed sample size was calculated to demonstrate a significant improvement in the intervention group compared to the control group with at least 80% power and a two‐sided 5% type 1 error. The authors have quoted a sample size of 44 patients and a 1:1 randomization design to allow for an approximate dropout rate of 10%. Therefore it is planned that 50 patients will be recruited: this will result in approximately 25 patients in the vildagliptin + metformin ‐ intervention group and in the placebo + metformin ‐ control group. The data from the study is planned to be pooled and summarized with respect to demographic and baseline characteristics and efficacy and safety observations. Exploratory analyses will be performed using descriptive statistics. Data will be presented for the complete intent‐to‐treat population (all patients having taken at least one dose of study medication) as well as the per‐protocol population (all patients who completed the study without major protocol deviations).
Participants	Inclusion criteria 1) Subjects ≥18 years of age diagnosed with diabetes (type 1 or 2) on diet only or any diabetic medication regime. 2) Existing diabetes index foot ulcer grade A1 or higher according to the University of Texas Wound Classification System of Diabetic Foot Ulcers on the day of study inclusion. A foot ulcer will be defined as any full thickness skin defect existing for at least 14 days. In patients with multiple diabetic foot ulcers the index foot ulcer is defined as the foot ulcer with the largest wound area at the time of inclusion. 3) A sub‐optimal HbA1c ≥ 7.0% documented somewhere in the patient source documents within 12 weeks prior to study inclusion or on the day of study inclusion. Exclusion criteria 1. Exclusion criteria will comply with local label 2. Clinical infection at the studied ulcer site (bacterial and fungal) 3. Planned surgical intervention for the ulcer 4. Hypersensitivity to either of the study drug components 5. History of lactic acidosis 6. Type 1 diabetes 7. Current HbA1c < 7 or > 9% 8. Current Insulin treatment. 9. Active treatment with GLP‐1 or other DPP4i medication 10. Use of thiazolidinediones, statins, anti‐inflammatory or anti‐platelet agents 11. Clinically significant lower‐extremity ischemia (as defined by an ankle/brachial index of < 0.65) 12. Significant medical conditions that would impair wound healing will also be excluded from the study. These conditions include hepatic, respiratory or cardiac failures, aplastic anemia, scleroderma and malignancy, treatment with immunosuppressive agents or steroids, myocardial infarcts, stroke, major surgery within six months of the study, usage of tobacco 13. Severe non‐proliferative or proliferative diabetic retinopathy 14. Active Charcot's foot as determined by clinical and radiographic examination 15. Ulcer of a non‐diabetic pathophysiology (e.g. rheumatoid, radiation‐related, and vasculitis‐related ulcers, calciphylaxis or dystrophic calcinosis cutis) 16. Active malignancy other than basal cell carcinoma as well as subjects with cancerous or pre‐cancerous lesions in the ulcer area 17. Renal dysfunction: eGFR < 60 ml/min 18. Chronic inflammation (inflammatory bowel disease, inflammatory or rheumatoid arthritis) 19. Pregnancy, lactation or child‐bearing potential 20. Recent venous thromboembolism 21. Inability to comply with study protocol
Interventions	Arm 1: (Intervention group) will be on oral metformin 500 mg to 3000 mg per oral in single or divided dosages (two or three times a day) plus vildagliptin 50 mg to 100 mg per day also to be administered orally for 12 weeks. The dosages of both medications will be determined based on blood glucose levels with the aim of achieving average fasting blood glucose of < 7 mmol/l and post‐prandial blood glucose of 10 mmol/l or below. Improved adherence will be enhanced by weekly clinic visit and drug tablet return as well as monitoring blood glucose control and progress of the diabetic foot ulcer. Arm 2: (Comparator group) will be on given metformin as described above plus placebo comprising lactose 50 mg to 100 mg per day to be taken orally for 12 weeks. The placebo will be identical in appearance to vildagliptin without the active ingredient.
Outcomes	Primary outcome: significant (20%) reduction of serum levels of IL‐6. IL‐6 will be quantified using the Multiplex FlowCytomix system (Bendermedsystems). Antibody‐coated beads will be incubated with either patient serum, followed by a biotin‐conjugated secondary antibody and finally streptavidin‐PE. The sample will be run on BD caliber. Analysis will be performed using software provided by the manufacturer. Secondary outcomes: a) Partial or complete closure of foot ulcer b) Worsening of the foot ulcer beyond Wagner grade 2 c) Requirement for limb or toe amputation These will be based on weekly measurement of the ulcer at the start (week 1) and week 12.
Starting date	1/08/2013
Contact information	Assoc. Professor Usman H. Malabu; FRCPI, FRACP. School of Medicine and Dentistry James Cook University & Townsville Hospital 100 Angus Smith Drive Douglas, Townsville QLD 4814,Australia
Notes	https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=364001 *All content above adapted from the published clinical trial record