Diabetic Foot Ulcer Wound Fluid Biomarker

糖尿病足溃疡伤口液生物标志物

• 批准号: 10612740
• 负责人: Sashwati Roy
• 金额: $ 2.44万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-25 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10612740
• 关键词: Adopted; Adoption; Adult; Algorithms; American; Amino Acids; Amputation; Ancillary Study; Area; Bathing; Bioinformatics; Biological Assay; Biological Markers; Biopsy; Blinded; Caring; Characteristics; Chronic; Clinical; Clinical Protocols; Collection; Complex; Complications of Diabetes Mellitus; Cysteine; Cystine; Data; Diabetes Mellitus; Diabetic Foot; Diabetic Foot Ulcer; Direct Costs; Environment; Equilibrium; Failure; Goals; High Pressure Liquid Chromatography; Home; Hospitalization; Hospitals; Impairment; Infection; Inflammation; Injury; Intervention; Liquid substance; Lower Extremity; Malignant Neoplasms; Mass Spectrum Analysis; Metabolic; Metabolism; Multi-site clinical study; Names; National Institute of Diabetes and Digestive and Kidney Diseases; Necrosis; Nitrogen; Outcome; Oxidation-Reduction; Oxidative Stress; Oxygen; Pathogenesis; Patients; Persons; Phase; Play; Population; Preparation; Protein Biosynthesis; Protocols documentation; Punch Biopsy; Refractory; Reporting; Rest; Running; Sample Size; Sampling; Site; Sulfhydryl Compounds; Testing; Time; Treatment Protocols; United States National Institutes of Health; Validation; Work; aggressive therapy; biobank; c-myc Genes; care costs; care providers; chronic ulcer; chronic wound; clinical biomarkers; clinical research site; demographics; diabetic patient; diabetic ulcer; experience; healing; improved; interest; limb amputation; limb loss; metabolomics; mortality; non-healing wounds; open wound; oxidation; participant enrollment; point of care; predictive marker; programs; prospective; protein function; research clinical testing; response; standard of care; statistics; tissue repair; working group; wound; wound care; wound healing

The 2020 CDC national diabetes statistics report identified that 34.2 million Americans, or 10.5% of the population had diabetes in 2018. It is estimated that over the course of their lifetime up to a third of these people with diabetes will develop a diabetic foot ulcer (DFU). The five-year mortality and direct costs of care for people with diabetic foot complications are comparable to cancer. Approximately 40-60% of nontraumatic lower limb amputations worldwide are caused by diabetic complications, and 80% of these amputations follow DFU. In patients with hard-to-heal DFUs, treatment with multiple therapies is often necessary to manage stubborn wounds. The current DFU treatment algorithm uses failure to improve (>50% wound area reduction) after four weeks of standard of care (SoC) therapy to make a clinical decision on changing the therapy. The lack of objective early indicators of wound healing outcomes handicaps DFU care strategy. Biomarkers that predict non- healing (i.e., refractory to SoC) would provide an objective basis for rationally adopting alternate treatment regimen to wound care providers in a timely manner. This proposal rests on our premise that non-healing diabetic wounds would suffer from metabolic impairments which in turn would be reflected by changes in metabolites contained in wound fluids (WF). A metabolomics approach was used to screen 578 metabolites from 161 WF from chronic wound patients. Of all these metabolites, ONE PARAMETER emerged as a robust predictor of non- healing: low Cysteine (Cys)/Cystine (CysS). A prospective preliminary study on DFU patients (N=24) showed that low Cys/CysS in WF predicts non-healing. A point-of-care microtiter-plate (standard hospital assay platform) based test was used. Because the proposed work seeks to establish Cysteine Redox as a biomarker of non- healing or Open wound, the study is named CREDO. The R61 preparatory phase is named 2CREDO (towards CREDO), and the R33 phase is referred to as CREDO. Aim 1: Validate the use DFU wound fluid low Cys/CysS ratio (<3.43 cut-off) as a primary biomarker to predict non-healing of DFU. Aim 2: Develop a complete clinical protocol to validate the use of Cys/CysS ratio in wound fluids to predict the healing of adult DFU. Aim 3: Conduct a multi-center clinical study of diabetic foot ulcer patients to perform detailed validation of wound fluid based Cys/CysS ratio as a biomarker to predict diabetic foot ulcer healing. Aim 4: Initiate discussions with FDA to establish Cys/CysS as a clinical biomarker to predict DFU healing. The proposed work will be conducted as ancillary Study of the current NIDDK Diabetic Foot Consortium (DFC) who have approved feasibility of our protocol.

2020年CDC国家糖尿病统计报告确定，有3420万美国人或10.5％的美国人 人口在2018年患有糖尿病。据估计，在这些人的一生中，这些人中有三分之一 使用糖尿病会发展出糖尿病足溃疡（DFU）。五年死亡率和人的直接护理费用 糖尿病脚并发症与癌症相当。大约40-60％的非创伤下肢 全球截肢是由糖尿病并发症引起的，其中80％的截肢遵循DFU。在 患有难以愈合的DFU的患者通常需要使用多种疗法治疗来治疗固执 伤口。当前的DFU治疗算法使用未能改善（> 50％伤口区域减少）。 数周的护理标准（SOC）治疗，以改变治疗的临床决定。缺乏 伤口愈合结果的客观早期指标残障DFU护理策略。预测非的生物标志物 康复（即对SOC的难治）将为合理采用替代治疗提供客观的基础 及时向伤口护理提供者提供方案。该提议基于我们的前提，即非治疗糖尿病 伤口将遭受代谢损害，而代谢物的变化将反映 包含在伤口流体（WF）中。一种代谢组学方法用于从161 WF筛选578代谢物 来自慢性伤口患者。在所有这些代谢物中，一个参数作为非 - 愈合：低半胱氨酸（CYS）/cystine（Cyss）。一项针对DFU患者的前瞻性初步研究（n = 24） WF中的低CYS/CYS预测了非污染。护理点的微量滴定板（标准医院测定平台） 使用了基于测试。因为拟议的工作旨在将半胱氨酸氧化还原建立为非 - 康复或开放性伤口，该研究名为Credo。 R61预备阶段命名为2Credo（朝向 Credo），R33阶段称为Credo。 AIM 1：验证使用DFU伤口流体低CYS/CYSS 比率（<3.43截止）作为预测DFU不污染的主要生物标志物。目标2：开发完整的临床 验证在伤口流体中使用CYS/CYSS比以预测成人DFU的愈合的方案。目标3：行为 糖尿病足溃疡患者的多中心临床研究详细验证了伤口基液 CYS/CYSS比率是预测糖尿病足溃疡愈合的生物标志物。目标4：与FDA进行讨论 建立CYS/CYSS作为临床生物标志物，以预测DFU愈合。拟议的工作将作为 批准我们的可行性的当前NIDDK糖尿病足财团（DFC）的辅助研究 协议。