DPP IV Inhibition Facilitates Healing of Chronic Foot Ulcers in Type 2 Diabetes

Chronic Foot Ulcers Clinical Trial

Official title:

Dipeptidyl Peptidase (DPP) IV Inhibition Facilitates Healing of Chronic Foot Ulcers in Patients With Type 2 Diabetes

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01472432
• Other study ID #: IT 345461
• Status: Active, not recruiting
• Phase: Phase 4
• First received: November 7, 2011
• Last updated: May 19, 2015
• Start date: May 2011
• Est. completion date: December 2016

Study information

• Verified date: May 2015
• Source: Second University of Naples
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 106
• Est. completion date: December 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Foot Ulcers
• Diabetes Mellitus, Type 2
• Foot Ulcer
• Ulcer

Intervention

Drug:
• placebo
Placebo is added to the standard good medical practice.
• vildagliptin
50 mg per os b.i.d. for 4 months of treatment, added to the standard good medical practice.

Locations

Country	Name	City	State
Italy	Second university of Naples	Naples

Sponsors (1)

Lead Sponsor	Collaborator
Second University of Naples

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Full Epithelialization of the Wound	Biopsy is 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.	4 months of treatment with vildagliptin	No
Primary	Capillary Density	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 is measured using immunohistochemistry	4 months of treatment with vildagliptin	No
Secondary	HIF-1a	The factor is assessed by immunoblot analysis (commercial kits). Arbitrary unit of measure are used.	4 months	No
Secondary	VEGF	The factor is assessed by immunoblot analysis (commercial kits). Arbitrary unit of measure are used.	4 months	No
Secondary	VEGF-R1 (Total and Phosphorylated Form)	The receptor is assessed by immunoblot analysis (commercial kits). Arbitrary unit of measure are used.	4 months	No
Secondary	VEGF-R2 (Total and Phosphorylated Form)	The receptor is assessed by immunoblot analysis (commercial kits). Arbitrary unit of measure are used	4 months	No
Secondary	iNOS	The factor is assessed by immunoblot analysis (commercial kits). Arbitrary unit of measure are used.	4 months	No