Admin Supplement Request for U01 DK119100-04

项目摘要 糖尿病足溃疡(DFU)是一种常见的、致残的和昂贵的疾病。它们是由 困扰糖尿病足的神经病变、免疫病变和血管病变。有15%-25%的人患有 糖尿病人一生中的某个时候会发生DFU，其中高达20%的DFU会导致严重的 截肢。DFU需要相当多的时间和资源来治愈，而高达80%的治愈者可能 发展复发。随着全球糖尿病患病率的持续增长，DFU的负担要求 更有效的预防和治疗方法。分子等领域不断发展的技术 医学、生物材料和生物传感器提供了改善预防和预后、加速 治愈，减少复发。然而，DFU的有效治疗方法的发展一直是 受阻于临床试验中的挑战，包括需要更好的分期、有效的替代生物标记物， 和标准化的终端。NIDDK正在建立糖尿病足联盟(DFC)，以解决 通过临床研究单位(CRU)网络，这一未得到满足的需求最初专注于生物标记物研究。在这 申请，研究人员建议加州大学旧金山分校糖尿病足临床研究单位，它利用一个 非常多样化的患者群体，世界一流的临床和转化科学机构，以及 经验丰富的多学科调查团队和工作人员。加州大学旧金山分校糖尿病足CRU包括 加州大学旧金山分校医学中心和扎克伯格旧金山综合医院(ZSFG) 医院作为综合演出场地。它建立在现有的临床和研究专业中心的基础上， 包括加州大学旧金山分校肢体保存中心；加州大学旧金山分校糖尿病中心；加州大学旧金山分校脆弱中心 ；加州大学旧金山分校临床和翻译科学研究所(CTSI)；以及NIDDK资助的 2型糖尿病转化研究(CDTR)。调查人员带来了广泛的专业知识 糖尿病、血管疾病、足科内科/外科、临床试验、研究测量 种族/社会经济多样化的患者，以及与以下疾病直接相关的生物标记物和伤口愈合研究 DFC的目标。他们提出了一个糖尿病足CRU，它将利用协调管理和 创新的临床研究战略，以解决三个具体目标：i)招募一名社会经济 DFU生物标志物研究的种族多样性和代表性人群；ii)保留受试者用于 重复测量的纵向队列研究；以及三)有效、有质量控制的样本和数据 收集以实现生物标记物验证研究。此外，调查人员将通过以下方式为DFC做出贡献 建议相关的生物标志物、技术、研究方案和试验设计，以促进临床 DFU护理的科学。

PROJECT ABSTRACT Diabetic foot ulcers (DFU) are a common, disabling, and costly condition. They result from a confluence of neuropathy, immunopathy, and vasculopathy that afflict the diabetic foot. Between 15-25% of individuals with diabetes will get a DFU at some point during their lifetime, and up to 20% of these DFUs will lead to a major limb amputation. DFUs require considerable time and resources to heal, and up to 80% of those that heal may develop recurrence. As the global prevalence of diabetes continues to grow, the burden of DFU mandates more effective prevention and treatment approaches. Evolving technologies in areas such as molecular medicine, biomaterials, and biosensors offer opportunities to improve prevention and prognosis, accelerate healing, and reduce recurrence. However, the development of effective treatments for DFU has been hampered by challenges in clinical trials, including the need for better staging, validated surrogate biomarkers, and standardized endpoints. The Diabetic Foot Consortium (DFC) is being established by NIDDK to address this unmet need via a network of Clinical Research Units (CRUs), initially focused on biomarker studies. In this application, the investigators propose the UCSF Diabetic Foot Clinical Research Unit, which leverages a very diverse patient population, world-class institutions for clinical and translational science, and an experienced, multi-disciplinary team of investigators and staff. The UCSF Diabetic Foot CRU includes the University of California, San Francisco (UCSF) Medical Center and Zuckerberg San Francisco General (ZSFG) Hospital as integrated performance sites. It builds upon existing centers of clinical and research expertise, including the UCSF Center for Limb Preservation; the UCSF Diabetes Center; the UCSF Center for Vulnerable Populations; the UCSF Clinical and Translational Science Institute (CTSI); and an NIDDK-funded Center for Type 2 Diabetes Translational Research (CDTR). The investigators bring a broad range of expertise in diabetes, vascular disease, podiatric medicine/surgery, clinical trials, research measurements in ethnically/socio-economically diverse patients, and biomarker and wound healing studies of direct relevance to the goals of the DFC. They propose a Diabetic Foot CRU that will utilize coordinated management and innovative clinical research strategies to address three Specific Aims: i) recruitment of a socio-economically and ethnically diverse and representative population for biomarker studies in DFU; ii) retention of subjects for longitudinal cohort studies with repeated measures; and iii) efficient, quality-controlled, sample and data collection to enable biomarker validation studies. In addition, the investigators will contribute to the DFC by suggesting relevant biomarkers, technologies, and study protocols and trial designs to advance the clinical science of DFU care.