Metabolomics and Wound Healing in Diabetes-Mechanisms and Clinical Value of Arginine Supplement in Patients With Diabetic Foot Ulcers
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 发起方
- 试验地点
- 2
- 主要终点
- PEDIS
研究概览
简要总结
The dysfunction of wound healing in diabetes involves multiple healing processes by diminished inflammatory responses and delayed deposition of matrix components, wound remodeling, and closure. Furthermore, hyperglycemia increases the infection susceptibility of wounds. In Taiwan, we have data demonstrating the nutrition status associated the outcome of diabetic foot ulcer (DFU) acute treatment and value of serum arginine level (in preliminary metabolomics study) to predict one-year healing of DFUs. The arginine has the beneficial effects on wound healing by the action of its metabolites, including vasodilatation, bactericide, growth factors recruitment and collage formation. Nevertheless, its supplement and mechanism in patients with diabetes is still remains unproven. This study aims at (1) defining the effects of arginine supplement, on top of the traditional treatment and risk reduction, on healing outcomes of patients with DFUs, (2) studying the modes of action of arginine supplements in diabetes, and (3) verifying the metabolomics factors and their association with wound healing prospects in patients with DFUs. A total of 120 patients with chronic diabetic foot ulcer will be enrolled and survey in 3 years. Along with standard of care, patients will receive, in a randomized fashion, either arginine (treatment group) or whey protein (control group) 5 g per day supplement for 4 weeks. The wound status will be collected with features in wound size, tissue perfusion, and infection status before and after treatment. Nutritional surveys, nitrogen balance as well as various molecular studies such as metabolomics analysis and neutrophil-to-lymphocyte ratio will be performed to study the association between the molecules of nutrients and the healing
详细描述
The dysfunction of wound healing in diabetes involves multiple healing processes by diminished inflammatory responses and delayed deposition of matrix components, wound remodeling, and closure. Furthermore, hyperglycemia increases the infection susceptibility of wounds. The wounds noted at distal limb of body, the diabetic foot ulcers, have more significant impacts clinically and socioeconomically compare to those injuries from surgery or pressure sores.
- Urge for Novel treatments in patients with diabetic foot ulcers:
1.1. Facts: Diabetic foot ulcer (DFU) is a major complication of diabetes that can lead to limb loss and premature death. According to a report from the International Diabetes Federation in 2017, DFU is also the most common cause of hospitalization for patients with diabetes.
In Taiwan, 1% of patients with diabetes are admitted to hospital for the treatment of DFU annually. However, considering that the lower-extremity amputation (LEA) rate is around 30%,the treatment outcomes are obviously unsatisfactory.
1.2. Standard treatment for DFU 1.2.1 In 2016, we formed a Taiwan national working group on diabetic foot under the authorization of Diabetes Association of the Republic of China and subsequently published a Diabetic foot guideline in Taiwan in 2017 (ISBN 978-986-82436-8-2). In addition, I also participated in the writing of a clinical foot care guideline released 2017 by International Diabetes Federation . 1.2.2 These two most updated guidelines detail the diagnosis, management and prevention for patients with DFUs with specifically focused on (1) infection, (2) peripheral artery diseases, (3) wound care and surgical intervention, and (4) off-loading and risks reduction. Suggestions for the appropriate medications for patients with various clinical characteristics were also provided. Nevertheless, in addition to treating acute infections and limb ischemia, the optimum healing of a foot ulcer requires treating the complex biological and molecular events of cell migration and proliferation, and of extracellular matrix deposition, remodeling, and tissue microcirculation. This is why the prognosis for patients with DFU is still unsatisfactory, worldwide. Novel treatments are therefore needed to provide better tissue healing in patients with diabetes. Unfortunately, recent results of well-designed novel treatments for patients with DFU have been disappointing. 2. The role of nutrition in wound healing The relationship between nutrition and wound healing, whether after injury or surgical intervention, has been recognized for centuries and adequate carbohydrate, fat and protein intake is known to be necessary for healing to take place. Wound failure, as reflected by wound infections and/or delayed healing, significantly contributes to the financial burden imposed on health care systems worldwide.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Health Services Research
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •are men or non-pregnant women, aged ≥ 40 years or ≤ 80 years
- •have a history of foot ulcers for more than 1 month
- •have a serum albumin level ≤ 4.0 or an ABI level ≤ 1
排除标准
- •Have active malignancy
- •Have acute gastrointestinal surgery
- •are receiving dialysis
- •have heart failure (NYHA Fc ≥ 3), liver cirrhosis (Child class > B), or myocardial infarction in the past 3 months,
- •have wounds complicated with persistent osteomyelitis or Charcot deformity
- •are receiving hydroxyurea or steroid treatment
- •have alcohol abuse, any mental or physiological condition that may interfere with dietary intake, and those who are unable to follow orders or cooperate.
结局指标
主要结局
PEDIS
时间窗: up to 1 months
Wound assessment was recorded using the PEDIS system
次要结局
未报告次要终点