Advancing an accessible, high-throughput and multiplex islet autoantibody test with self-collected capillary dried blood spots for regulatory clearance

利用自我收集的毛细血管干血点推进易于使用、高通量和多重胰岛自身抗体测试，以供监管审批

• 批准号: 10699934
• 负责人: David Seftel
• 金额: $ 99万
• 依托单位: ENABLE BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10699934
• 关键词: Affect; Agglutination; American; Autoantibodies; Autoimmune Diseases; Award; Bilirubin; Biological Assay; Biological Markers; Biological Sciences; Blinded; Blood; Blood capillaries; Chronic; Clinical; Clinical Research; Collaborations; Collection; Data; Dependence; Devices; Diabetes Mellitus; Diabetes autoantibodies; Diabetic Ketoacidosis; Diagnosis; Dryness; Eligibility Determination; Enrollment; Hemoglobin; Home; Hybridomas; IA-2 antibody; Individual; Insulin; Insulin-Dependent Diabetes Mellitus; Intervention; Islet Cell; Laboratories; Legal patent; Life; Lipids; Longevity; Methods; National Institute of Diabetes and Digestive and Kidney Diseases; Organ; Pancreas; Pathway interactions; Performance; Persons; Phase; Plasma; Process; Production; Protocols documentation; Publishing Peer Reviews; Reagent; Regulation; Reporting; Reproducibility; Risk; Risk Factors; Sampling; Serum; Signal Transduction; Site; Small Business Innovation Research Grant; Specific qualifier value; Speed; Spottings; Symptoms; System; Technology; Testing; Validation; Whole Blood; antibody detection; design; detection assay; detection limit; diabetes risk; hazard; innovation; insulin dependent diabetes mellitus onset; islet cell antibody; manufacture; manufacturing quality; manufacturing test; prevent; sample collection; screening program; success; usability; validation studies

Project Summary Type 1 diabetes, a chronic autoimmune disorder that affects millions of Americans is characterized by the progressive destruction of the insulin-producing islet cells of the pancreas, resulting in life-long dependency on insulin therapy. Many people with type 1 diabetes are diagnosed with life-threatening diabetic ketoacidosis and develop a panoply of perilous complications affecting every organ over their shortened life spans. Testing for the presence of anti-islet autoantibody biomarkers in blood accurately predicts whether individuals are at risk for developing type 1 diabetes. Autoantibody screening programs have been shown to support interventions that reduce the rates of diabetic ketoacidosis and they help identify eligible candidates for new interventions that may delay or prevent the onset of type 1 diabetes. However, no current testing method exists that combines accuracy, speed, scalability, and the ability to collect samples at home. In application is a follow-on to Enable Biosciences Phase 2 NIDDK SBIR Award R44DK111005 Phase 2B application we are seeking NIDDK support for the process of FDA clearance and comprehensive quality system implementation of our unique dried blood spot test for T1D autoantibodies based on our innovative patented Antibody Detection by Agglutination-PCR (ADAP) technology. ADAP is highly sensitive and ultra-specific and has been repeatedly validated as a top-performing T1D autoantibody assay in blinded peer-reviewed published clinical studies. In Specific Aim 1, we will develop a comprehensive quality system to allow for reliable and high-quality manufacturing of test components to be used for the FDA study. Reagents, materials, protocols, and document control systems will be developed and documented in compliance with FDA requirements. In Specific Aim 2, we will perform standard laboratory analytical validation of the assay, determining the reproducibility, limit of blank, limit of detection and limit of quantification, as well as performing interference analysis by spiking in common adulterants into test samples. In Specific Aim 3, we will perform our clinical validation in collaboration with nationwide and, if needed, global clinical specimen collection sites to establish non-inferiority with the predicate device. . For this

项目摘要 1型糖尿病，一种影响数百万美国人的慢性自身免疫性疾病的特征是 胰腺产生胰岛素胰岛细胞的进行性破坏，导致终身 依赖胰岛素​​治疗。许多1型糖尿病的人被诊断出患有生命 糖尿病性酮症酸中毒并发展出危险的并发症，影响每个器官的每个器官 缩短了寿命。测试血液中抗ISLET自身抗体生物标志物的存在 预测个人是否有患1型糖尿病的风险。自动抗体筛选程序 已显示支持降低糖尿病酮症酸中毒率的干预措施，它们有助于 确定可能延迟或阻止1型糖尿病发作的新干预措施的合格候选人。 但是，目前的测试方法不存在结合准确性，速度，可伸缩性和能力 在家收集样品。 在应用中是启用生物科学阶段2 NIDDK SBIR奖R44DK111005的后续后续行动 2B阶段应用我们正在寻求NIDDK对FDA清除过程的支持和 我们针对T1D自动抗体的独特的干血点测试的全面质量系统实施 基于我们通过凝集-PCR（ADAP）技术创新的专利抗体检测。贴花 高度敏感和超特异性，已被反复验证为表现最好的T1D 经同行评审发表的临床研究中的自身抗体测定。 在特定目标1中，我们将开发一个综合质量系统，以允许可靠和高质量 用于FDA研究的测试组件的制造。试剂，材料，协议和 文档控制系统将根据FDA要求制定和记录。 在特定目标2中，我们将对测定法进行标准的实验室分析验证，以确定 可重复性，空白的限制，检测极限和定量限制以及执行 通过将共同掺假物刺激到测试样本中的干扰分析。 在特定的目标3中，我们将与全国合作进行临床验证，并在需要时， 全球临床标本收集位点与谓词设备建立不劣效率。 。为了这