Dipeptidyl Peptidase (DPP) IV Inhibition Facilitates Healing of Chronic Foot Ulcers in Patients With Type 2 Diabetes
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 106
- 试验地点
- 1
- 主要终点
- Full Epithelialization of the Wound
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Placebo
In the placebo group, the dose of other concomitant hypoglycemic medication was changed to obtain a similar profile of metabolic parameters. 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.
干预措施: Placebo (Drug)
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
干预措施: vildagliptin (Drug)
结局指标
主要结局
Full Epithelialization of the Wound
时间窗: 3 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. Optic microscopy is used to evaluate the epithelialization of the wound.
Capillary Density
时间窗: 3 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 is measured using immunohistochemistry
次要结局
- HIF-1α(3 months)
- VEGF(3 months)
- VEGF-R1 (Total and Phosphorylated Form), VEGF-R2 (Total and Phosphorylated Form)(3 months)
- iNOS(3 months)
研究者
Raffaele Marfella
Assistant Professor
University of Campania "Luigi Vanvitelli"