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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Raffaele Marfella, Second University of Naples
ClinicalTrials.gov Identifier:
NCT01472432
First received: November 7, 2011
Last updated: November 15, 2011
Last verified: November 2011
History of Changes
  Purpose

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.


Condition Intervention Phase
Chronic Foot Ulcers
 Drug: placebo
Drug: vildagliptin
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Dipeptidyl Peptidase (DPP) IV Inhibition Facilitates Healing of Chronic Foot Ulcers in Patients With Type 2 Diabetes

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Second University of Naples:

Primary Outcome Measures:
  • Full epithelialization of the wound [ Time Frame: 4 months of treatment with vildagliptin ] [ Designated as safety issue: No ]

    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.


  • Capillary density [ Time Frame: 4 months of treatment with vildagliptin ] [ Designated as safety issue: No ]

    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



Secondary Outcome Measures:
  • HIF-1α [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    The factor is assessed by immunoblot analysis (commercial kits). Arbitrary unit of measure are used.

  • VEGF [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    The factor is assessed by immunoblot analysis (commercial kits). Arbitrary unit of measure are used.

  • VEGF-R1 (total and phosphorylated form) [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    The receptor is assessed by immunoblot analysis (commercial kits). Arbitrary unit of measure are used.

  • VEGF-R2 (total and phosphorylated form) [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    The receptor is assessed by immunoblot analysis (commercial kits). Arbitrary unit of measure are used

  • iNOS [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    The factor is assessed by immunoblot analysis (commercial kits). Arbitrary unit of measure are used.


Estimated Enrollment: 106
Study Start Date: May 2011
Estimated Study Completion Date: December 2011
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
In the placebo group, the dose of other concomitant hypoglycemic medication was changed to obtain a similar profile of metabolic parameters. Additional antidiabetic therapy, including sulfonylurea, metformin, and insulin, was titrated for optimal glycemic control for 3 months. All patients had diabetes and at least one full-thickness wound below the ankle for >3 months. All patients were examined weekly for the first 4 weeks (day 28) then every other week until day 120 or ulcer closure by any means. At each visit, tracings of the wound margins were made for computer planimetry to document changes in wound size, and photographs were taken for a visual record. All patients followed the regular treatment at the multidisciplinary diabetes foot clinic, included treatment of infection, debridement, off-loading, and metabolic control according to high international standards and standard good medical practice.
 Drug: placebo
Placebo is added to the standard good medical practice.
Experimental: Vildagliptin
The experimental arm followed the same treatment of placebo group, but received also vildagliptin 50 mg per os b.i.d. for 4 months
 Drug: vildagliptin
50 mg per os b.i.d. for 4 months of treatment, added to the standard good medical practice.

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

Ages Eligible for Study:   40 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01472432

Locations
Italy
Second university of Naples
Naples, Italy, I-80100
Sponsors and Collaborators
Second University of Naples
  More Information

No publications provided

Responsible Party: Raffaele Marfella, Assistant Professor, Second University of Naples
ClinicalTrials.gov Identifier: NCT01472432     History of Changes
Other Study ID Numbers: IT 345461
Study First Received: November 7, 2011
Last Updated: November 15, 2011
Health Authority: Italy: Ethics Committee

Keywords provided by Second University of Naples:
type 2 diabetes
healing
foot ulcers
vildagliptin

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Ulcer
Foot Ulcer
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pathologic Processes
Foot Diseases
Skin Diseases
 Leg Ulcer
Skin Ulcer
Vildagliptin
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 21, 2013