Diabetic Foot Ulcer Wound Fluid Biomarker

糖尿病足溃疡伤口液生物标志物

基本信息

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
项目类别：
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

项目摘要

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指出，有 3420 万美国人，即 10.5% 2018 年，有 1/3 的人患有糖尿病。据估计，其中三分之一的人一生中患有糖尿病糖尿病患者会出现糖尿病足溃疡（DFU）。人们的五年死亡率和直接护理成本糖尿病足的并发症与癌症相当。大约 40-60% 的非外伤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 DFU 造成的。在对于难以治愈的 DFU 患者，通常需要采用多种疗法来控制顽固的病情伤口。目前的 DFU 治疗算法使用四次后未能改善（>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。缺乏伤口愈合结果的客观早期指标阻碍了 DFU 护理策略。预测非的生物标志物治愈（即难治性 SoC）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治疗方案。该提议的前提是，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物的变化反映出来伤口液（WF）中含有。使用代谢组学方法从 161 个 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，有一个参数成为非代谢物的有力预测因子。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 中的 Cys/CysS 较低预示着不愈合。护理点微量滴定板（标准医院检测平台）使用基于测试。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（面向 CREDO），R33相称为CREDO。目标 1：验证使用低 Cys/CysS 的 DFU 伤口液比率（<3.43 截止值）作为预测 DFU 不愈合的主要生物标志物。目标2：开发完整的临床验证使用伤口液中的 Cys/CysS 比率来预测成人 DFU 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，以基于伤口液体进行详细验证 Cys/CysS 比率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。拟议的工作将按目前 NIDDK 糖尿病足联盟 (DFC) 的辅助研究已批准我们的可行性协议。