None listed
Conditions
Brief summary
Diabetic patients are at a particularly high risk for poor wound healing in general and foot ulcer in particular. The lifetime risk for developing chronic foot ulcer has been estimated to reach about 15-20% (1). Despite considerable advances in diabetic care, foot ulcers continue to be responsible for a high number of lower limb amputations that are associated with decrease in quality of life and increased risk of mortality (2). The major risk factors for diabetic foot ulcer (DFU) are polyneuropathy and peripheral vascular disease. Diabetes induces complex vascular changes, promoting accelerated atherosclerosis and hypercoagulability complicating foot ulcer which can be assessed indirectly by a number of inflammatory markers. Animal studies have suggested numerous beneficial anti-inflammatory effects of dipeptidyl peptidase-4 inhibitors (DPP4i), well beyond the effects on blood glucose alone (3). Interestingly, investigation on anti-inflammatory property of DPP4i-vildagliptin in human setting is scanty (4). Treatment with a DPP4i may offer an attractive blood glucose reduction with synergistic mechanism of action while exerting additional wound healing properties. Reduction of inflammatory marker levels is of great clinical importance and may correlate with improvement of diabetic wound healing. Therefore, in the present study we plan to focus on possible anti inflammatory properties of DPP4i in subjects with DFU. Primary objective: To demonstrate that Vildagliptin therapy is associated with clinically significant reduction in biological markers of inflammation compared to placebo in patients with DFU. Our Primary aim is demonstration of a significant (= 20%) reduction in the serum levels of interleukin 6 (IL-6). Secondary objectives: Partial or complete closure of foot ulcer or improvement in other biological markers of inflammation including: hs-CRP, platelet reactivity testing, TNF-alpha, interleukin 1 beta (IL-1 beta), adiponectin and tissue TGF- beta-1 levels. References 1. Lavery LA, et al. Diabetes Care. 2006:1288. 2. Singh N, et al. JAMA 2005: 293:217. 3. Shah Z, et al. Circulation. 2011: 124:2338. 4. Rizzo MR, et al. Diabetes Care. 2012: 35:2076.
Interventions
Arm 1: (Intervention group) will be on oral Metformin 500 mg to 3000 mg per oral in single or divided dosages (2 or 3 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 re
Arm 1: (Intervention group) will be on oral Metformin 500 mg to 3000 mg per oral in single or divided dosages (2 or 3 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.
Sponsors
Assoc. Professor Usman H. Malabu; FRCPI, FRACP.
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
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 is 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 suboptimal 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 DFU 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 6 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
Outcome results
None listed