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年疾病预防控制中心的全国糖尿病统计报告指出，3420万美国人，或10.5%的糖尿病患者