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.

2020年CDC国家糖尿病统计报告确定，3420万美国人，或10.5%的 2018年糖尿病患者人数据估计，在他们的一生中，多达三分之一的人 糖尿病患者会患上糖尿病足溃疡（DFU）。五年死亡率和直接护理费用 糖尿病足并发症与癌症相当。约40-60%的非创伤性下肢 全世界的截肢都是由糖尿病并发症引起的，其中80%的截肢是在DFU之后进行的。在 对于难以治愈的DFU患者，通常需要采用多种治疗方法来管理顽固的DFU。 伤口目前的DFU治疗算法使用失败来改善（>50%的伤口面积减少）， 标准治疗（SoC）治疗的一周，以做出改变治疗的临床决定。缺乏 伤口愈合结果的客观早期指标妨碍DFU护理策略。生物标记物预测非 愈合（即，难治性）为合理采用交替治疗提供了客观依据 及时向伤口护理提供者提供治疗方案。这项建议基于我们的前提，即非愈合性糖尿病 伤口将遭受代谢损伤，这反过来将通过代谢物的变化来反映 包含在伤口流体（WF）中。用代谢组学方法从161个野生型中筛选出578个代谢产物 从慢性创伤患者。在所有这些代谢物中，有一个参数是非代谢物的可靠预测因子。 愈合：低半胱氨酸（Cys）/胱氨酸（CysS）。一项针对DFU患者（N=24）的前瞻性初步研究显示， WF中低Cys/CysS预示不愈合。床旁微量滴定板（标准医院分析平台） 使用了基于测试。因为拟议的工作旨在建立半胱氨酸氧化还原作为非生物标志物， 愈合或开放性伤口，该研究被命名为CREDO。R61准备阶段被命名为2CREDO（朝向 CREDO），并且R33相被称为CREDO。目的1：使用DFU伤口液低Cys/CysS 比值（<3.43临界值）作为预测DFU不愈合的主要生物标志物。目标2：制定完整的临床 验证使用伤口流体中的Cys/CysS比率来预测成人DFU的愈合的方案。目标3：行为 一项针对糖尿病足溃疡患者的多中心临床研究，对基于伤口液的 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：启动与FDA的讨论， 建立Cys/CysS作为预测DFU愈合的临床生物标志物。拟议的工作将按照 目前NIDDK糖尿病足联盟（DFC）的辅助研究，他们已经批准了我们的可行性， 议定书