NCT01472432.

Trial name or title	DPP IV inhibition facilitates healing of chronic foot ulcers in type 2 diabetes
Methods	This study is a randomized versus placebo trial designed to evaluate the clinical and humoral effects of four months of vildagliptin on healing of chronic ulcers in type 2 diabetes. Both micro and macroangiopathy strongly contribute to development and delayed healing of diabetic wounds, through an impaired tissue feeding and response to ischemia. HIF‐1α and VEGF, as well as the NO production from iNOS, may contribute to limitation of hypoxic injury by promoting angiogenesis and wound healing. Experimental and pathological studies suggest that the incretin hormone glucagon‐like peptide‐1 (GLP‐1) may improve VEGF generation, and promote pancreatic islet viability through the up‐regulation of HIF1α.Therefore, the aim of this study is to evaluate the effect of the augmentation of GLP‐1, by inhibitors of the dipeptidyl peptidase IV (DPP‐4), such as vildagliptin, on HIF‐1α, VEGF and iNOS in diabetic chronic ulcers.
Participants	Inclusion Criteria Type 2 diabetes Oral hypoglycaemic agents treatment Chronic foot ulcers Adequate blood circulation (perfusion) assessed by a dorsum transcutaneous oxygen test > 30 ‐mmHg, ankle brachial index values > 0.7 and < 1.2 with toe pressure > 30 mmHg, or Doppler arterial waveforms that were triphasic or biphasic at the ankle of the affected leg Written consensus Exclusion Criteria Active Charcot disease Ulcers resulting from electrical, chemical, or radiation burns Collagen vascular disease Ulcer malignancy Untreated osteomyelitis, or cellulitis Ulcer treatment with normothermic or hyperbaric oxygen therapy Concomitant medications such as corticosteroids, immunosuppressive medications, or chemotherapy Recombinant or autologous growth factor products Skin and dermal substitutes within 30 days of study start Use of any enzymatic debridement treatments Pregnant or nursing mothers
Interventions	Experimenta group: vildagliptin The experimental arm will follow the treatment of placebo group, but received also vildagliptin 50 mg per os b.i.d. for four months. Placebo group: the dose of other concomitant hypoglycaemic medication will be changed to obtain a similar profile of metabolic parameters. Additional antidiabetic therapy, including sulphonylurea, metformin, and insulin, was titrated for optimal glycaemic control for three months. All patients will have diabetes and at least one full‐thickness wound below the ankle for > 3 months. All patients will be examined weekly for the first four weeks (day 28) then every other week until day 120 or ulcer closure by any means. At each visit, tracings of the wound margins will be made for computer planimetry to document changes in wound size, and photographs will be taken for a visual record. All patients will be followed up for regular treatment at the multidisciplinary diabetic foot clinic, included treatment of infection, debridement, off‐loading, and metabolic control according to high international standards and standard good medical practice.
Outcomes	Primary Outcome Measures Full epithelialization of the wound [ Time Frame: 4 months of treatment with vildagliptin ] [A biopsy will be performed from the periphery of the ulcer, before and after treatment with vildagliptin, in order to evaluate the above referred outcome. Optic microscopy is used to evaluate the epithelialization of the wound. Capillary density [ Time Frame: 4 months of treatment with vildagliptin].Biopsy is performed from the periphery of the ulcer, before and after treatment with vildagliptin, in order to evaluate the above referred outcome. Capillary density will be measured using immunohistochemistry Secondary Outcome Measures: HIF‐1α [ Time Frame: 4 months]. The factor will be assessed by immunoblot analysis (commercial kits). Arbitrary unit of measure will be used. VEGF [ Time Frame: 4 months ].The factor will be assessed by immunoblot analysis (commercial kits). Arbitrary unit of measure will be used. VEGF‐R1 (total and phosphorylated form) [ Time Frame: 4 months ]. The receptor will be assessed by immunoblot analysis (commercial kits). Arbitrary unit of measure will be used. VEGF‐R2 (total and phosphorylated form) [ Time Frame: 4 months ]. The receptor will be assessed by immunoblot analysis (commercial kits). Arbitrary unit of measure will be used. iNOS [ Time Frame: 4 months ]. The factor will be assessed by immunoblot analysis (commercial kits). Arbitrary unit of measure will be used.
Starting date	Unknown, last updated November 15, 2011
Contact information	Raffaele Marfella, Assistant Professor, Second University of Naples Second University of Naples Naples, Italy, I‐80100
Notes	https://clinicaltrials.gov/ct2/archive/NCT01472432 *All content above adapted from the published clinical trial record

The information for the ongoing trials listed in the table above was adapted directly from the clinical trial registration source referenced in the notes section.