Clinical trial NCT01472432: DPP IV Inhibition Facilitates Healing of Chronic Foot Ulcers in Type 2 Diabetes
Official title: Dipeptidyl Peptidase (DPP) IV Inhibition Facilitates Healing of Chronic Foot Ulcers in Patients With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Foot Ulcers
Keywords: type 2 diabetes
healing
foot ulcers
vildagliptin
Lead sponsor: University of Campania Luigi Vanvitelli
Sponsor class: OTHER
First posted: 2011-11-16
Enrollment: 106
Sex: ALL
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A randomized versus placebo trial designed to evaluate the clinical and humoral effects of 4 months of vildagliptin on healing of chronic ulcers in type 2 diabetes.

Detailed description: The chronic foot ulcer is a leading cause of hospital admissions for people with diabetes in the developed world and is a major morbidity associated with diabetes, often leading to pain, suffering, and a poor quality of life for patients. Chronic diabetic foot ulcers are estimated to occur in 15% of all patients with diabetes and precede 84% of all diabetes-related lower-leg amputations.The pathophysiology of chronic diabetic ulcers is complex and still incompletely understood, the most important predisposing factors being diabetic neuropathy and vasculopathy. 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 suggest that he incretin hormone glucagon-like peptide-1 (GLP-1) may improves VEGF generation, and promote pancreatic islet viability through the up-regulation of HIF1α.

Therefore, 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.

Eligibility criteria: Inclusion Criteria:

* Type 2 diabetes
* Oral hypoglycemic agents treatment
* Chronic foot ulcers
* Adequate blood circulation (perfusion) was assessed by a dorsum transcutaneous oxygen test \>30 -mmHg, anklebrachial index values \> 0.7 and \< 1.2 with toe pressure \> 30 mmHg, or Doppler arterial aveforms 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

Primary outcomes:
measure: Full Epithelialization of the Wound
timeFrame: 3 months of treatment with vildagliptin
measure: Capillary Density
timeFrame: 3 months of treatment with vildagliptin
Secondary outcomes:
measure: HIF-1α
timeFrame: 3 months
measure: VEGF
timeFrame: 3 months
measure: VEGF-R1 (Total and Phosphorylated Form), VEGF-R2 (Total and Phosphorylated Form)
timeFrame: 3 months
measure: iNOS
timeFrame: 3 months
Other outcomes:
Locations:
city: Naples
country: Italy
facility: Second university of Naples
Study officials:
affiliation: Second University Naples
name: Raffaele Marfella, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Marfella R, Sasso FC, Rizzo MR, Paolisso P, Barbieri M, Padovano V, Carbonara O, Gualdiero P, Petronella P, Ferraraccio F, Petrella A, Canonico R, Campitiello F, Della Corte A, Paolisso G, Canonico S. Dipeptidyl peptidase 4 inhibition may facilitate healing of chronic foot ulcers in patients with type 2 diabetes. Exp Diabetes Res. 2012;2012:892706. doi: 10.1155/2012/892706. Epub 2012 Nov 1.