Diabetic Foot Ulcer Wound Fluid Biomarker

糖尿病足溃疡伤口液生物标志物

• 批准号: 10396775
• 负责人: Sashwati Roy
• 金额: $ 48.59万
• 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 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10396775
• 关键词: Adopted; Adoption; Adult; Algorithms; American; Amino Acids; Amputation; Ancillary Study; Area; Bioinformatics; Biological Assay; Biological Markers; Biopsy; Blinded; Caring; Centers for Disease Control and Prevention (U.S.); Characteristics; Chronic; Clinical; Clinical Protocols; Collection; Complex; Complications of Diabetes Mellitus; Cysteine; Cystine; Data; Diabetes Mellitus; Diabetic Foot; Diabetic Foot Ulcer; Direct Costs; Enrollment; Environment; Equilibrium; Failure; Goals; Gold; Home; Hospitalization; Hospitals; Impairment; Infection; Inflammation; Intervention; Limb structure; Liquid Chromatography; 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; Nitrogen; Outcome; Oxidation-Reduction; Oxidative Stress; Oxides; Oxygen; Pathogenesis; Patients; Performance; Persons; Phase; Play; Population; Preparation; Protein Biosynthesis; Protocols documentation; Punch Biopsy; Refractory; Reporting; Rest; Running; Sample Size; Sampling; Site; Sulfhydryl Compounds; Testing; Time; Tissues; Treatment Protocols; United States National Institutes of Health; Validation; Work; aggressive therapy; base; biobank; c-myc Genes; care costs; care providers; chronic ulcer; chronic wound; clinical biomarkers; clinical research site; demographics; diabetic patient; experience; healing; improved; interest; limb amputation; limb loss; metabolomics; mortality; non-healing wounds; open wound; oxidation; point of care; predictive marker; programs; prospective; research clinical testing; response; skin ulcer; 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.

CDC 2020年全国糖尿病统计报告指出，3420万美国人，即10.5%的美国人 2018年人口患有糖尿病。据估计，在他们的一生中，多达三分之一的人 患有糖尿病的人会发展成糖尿病足溃疡(DFU)。五年死亡率和人们护理的直接成本 糖尿病足的并发症与癌症相当。约40%-60%的非创伤性肢体 世界各地的截肢手术都是由糖尿病并发症引起的，其中80%的截肢手术是在DFU之后进行的。在……里面 患有难以治愈的DFU的患者，通常需要采用多种治疗方法来管理顽固 伤口。当前的DFU治疗算法使用四次失败后改善(&gt；50%伤口面积减少) 数周的标准护理(SOC)治疗，以做出改变治疗的临床决定。缺乏 目的创面愈合结果的早期指标阻碍了DFU的护理策略。生物标志物可以预测非 治愈(即SOC的难治性)将为合理采用替代治疗提供客观依据 及时向伤口护理人员提供养生方案。这项提议基于我们的前提，即无法治愈的糖尿病患者 伤口会遭受代谢损伤，而代谢损伤又会通过代谢产物的变化反映出来。 包含在伤口液(WF)中。使用代谢组学方法从161名WF中筛选出578种代谢物 来自慢性伤口患者。在所有这些代谢物中，有一个参数是非 愈合：低半胱氨酸(Cys)/半胱氨酸(CysS)。一项对24例DFU患者的前瞻性初步研究显示 WF中低的Cys/CysS预示着无法愈合。医疗点微量试板(标准医院化验平台) 采用基于实验的测试方法。因为拟议的工作旨在将半胱氨酸氧化还原确立为非 无论是愈合还是开放创伤，这项研究被命名为CREDO。R61准备阶段被命名为2CREDO(朝向 CREDO)，R33阶段称为CREDO。目的1：验证DFU创面液低半胱氨酸/半胱氨酸的使用 Ratio(&lt；3.43截断值)作为预测DFU无法愈合的主要生物标志物。目标2：建立一个完整的临床 验证伤口液中Cys/CysS比率预测成人DFU愈合的方案。目标3：行为 一项对糖尿病足溃疡患者进行伤口液详细验证的多中心临床研究 Cys/CysS比值作为预测糖尿病足溃疡愈合的生物标志物。目标4：发起与FDA的讨论以 建立Cys/CysS作为预测DFU愈合的临床生物标志物。拟议的工作将按以下方式进行 目前NIDDK糖尿病足联盟(DFC)已批准我们的可行性的辅助研究 协议。