Continuous Glucose Monitoring with a Subcutaneous, Non-enzymatic Fluorescent Sens

描述（由申请人提供）：青少年糖尿病研究基金会（JDRF）估计，在美国多达300万人可能患有1型糖尿病。最近的大型临床试验已经证明了连续血糖监测仪（cgm）的治疗益处，从而增加了这些设备的保险报销的可用性。目前估计有50,000名糖尿病患者使用cgm，但随着胰岛素泵用户将他们的设备换成集成cgm的下一代泵，预计采用人数将稳步增长至250,000人。这代表着5亿美元的市场机会。然而，目前可用的cgm存在技术缺陷，限制了近期广泛的临床应用和人工胰腺的长期进展。这些限制包括低血糖范围的不准确性、频繁的校准要求和长时间的运行时间。更重要的是，人工胰腺的最终成功商业化可能需要使用多个冗余传感器以确保安全。在这种情况下，使用非酶的冗余传感器可能具有实质性的优势，即避免共模故障。GluMetrics是一家风险投资支持的公司，开发胰高血糖血管内连续血糖监测系统（胰高血糖系统）。该传感器采用一种新型的猝灭荧光化学机制，通过光纤展开。胰高血糖系统设计用于接受强化胰岛素治疗的危重患者。临床可行性已在52名健康的1型糖尿病志愿者中进行了长达24小时的持续试验。在这些研究中，胰高血糖传感器被放置在手臂的外周静脉中。结果与参考葡萄糖分析仪非常吻合，平均绝对相对差（MARD）为7.5%，94.7%的结果符合克拉克误差网格的临床准确a区，95%的结果符合ISO 15197标准的准确性标准。提出的研究是修改胰高血糖素传感器用于皮下组织。第一阶段项目的目标是在动物模型中演示皮下胰高血糖素传感器24小时的性能。随后的第二阶段工作将包括在延长时间的人体临床研究中演示安全性和有效性，以及小型化光学和电子元件和合适的自动插入装置的原型开发。

DESCRIPTION (provided by applicant): The Juvenile Diabetes Research Foundation (JDRF) estimates that up to 3 million people in the United States may have Type 1 diabetes. Recent large clinical trials have demonstrated the therapeutic benefits of continuous glucose monitors (CGMs), leading the way to increased availability of insurance reimbursement of these devices. An estimated 50,000 people with diabetes currently use CGMs, but adoption is forecast to grow steadily to 250,000 users as insulin pump users exchange their devices for next generation pumps with integrated CGMs. This represents a $500 million market opportunity. However, currently available CGMs have technical shortcomings that limit both near-term widespread clinical adoption and longer-term progress towards an artificial pancreas. These limitations include inaccuracy in the hypoglycemic range, frequent calibration requirements, and long run-in times. More importantly, the eventual successful commercialization of an artificial pancreas will likely require the use of multiple redundant sensors for safety. There could be substantial advantages associated with the use of a non-enzymatic, redundant sensor in this context, namely, avoidance of common mode failures. GluMetrics is a venture capital-backed company developing the GluCath Intravascular Continuous Glucose Monitoring System (GluCath System). The sensor in this device uses a novel quenched fluorescence chemical mechanism deployed via an optical fiber. The GluCath System is designed for use in critically-ill patients undergoing intensive insulin therapy. Clinical feasibility has been demonstrated in fifty-two healthy volunteer subjects with Type 1 diabetes mellitus for up to 24 h duration. In these studies, the GluCath sensor was placed in a peripheral vein in the arm. The results agreed closely with a reference glucose analyzer with a 7.5% mean absolute relative difference (MARD), 94.7% of results in the clinically accurate A region of the Clarke Error Grid and 95% of results meeting the accuracy criteria of the ISO 15197 standard. The proposed research is to modify the GluCath sensor for use in subcutaneous tissue. The objective of this phase I project is to demonstrate performance of a subcutaneous GluCath sensor in an animal model for 24 h. Subsequent phase II work will include the demonstration of safety and efficacy in extended duration human clinical studies and prototype development of miniaturized optical and electrical components and a suitable automated insertion device. PUBLIC HEALTH RELEVANCE: An estimated 3 million Americans have Type 1 diabetes. Continuous glucose monitors have been shown to provide significant therapeutic advantages, but current enzymatic sensor technologies have had limited clinical adoption and may not be sufficiently accurate for closed loop control. GluMetrics proposes to develop a novel and more accurate non-enzymatic based glucose sensor capable of achieving a high level of clinical accuracy over the entire physiological range (40 to 400 mg/dL), but especially in the hypoglycemic range (< 70 mg/dL).