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，美国可能有多达300万人患有1型糖尿病。最近的大型临床试验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。据估计，目前有5万糖尿病患者使用CGMS，但随着胰岛素泵用户将他们的设备更换为集成CGMS的下一代泵，采用率预计将稳步增长至25万用户。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，既限制了近期广泛的临床应用，也限制了人工胰腺的长期进展。这些限制包括降糖范围的不准确、频繁的校准要求和较长的磨合时间。更重要的是，人工胰腺的最终成功商业化很可能需要使用多个冗余传感器来保证安全。在这种情况下，使用非酶冗余传感器可能有很大的好处，即避免共模故障。GluMetrics是一家风险资本支持的公司，开发GluCath血管内持续血糖监测系统(GluCath系统)。该装置中的传感器采用了一种通过光纤布设的新型猝灭荧光化学机制。GluCath系统是为接受强化胰岛素治疗的危重患者设计的。临床可行性已经在52名患有1型糖尿病的健康志愿者身上得到证实，持续时间长达24小时。在这些研究中，GluCath传感器被放置在手臂的外周静脉中。结果与标准葡萄糖分析仪的结果非常一致，平均绝对相对差值为7.5%，94.7%的结果符合克拉克误差网格的临床准确A区，95%的结果满足ISO 15197标准的准确度标准。这项拟议的研究是为了改进GluCath传感器，使其用于皮下组织。该第一阶段项目的目标是在动物模型中展示皮下GluCath传感器的24小时性能。随后的第二阶段工作将包括在更长时间的人体临床研究中展示安全性和有效性，以及微型光学和电子部件以及合适的自动插入设备的原型开发。 与公共健康相关：估计有300万美国人患有1型糖尿病。连续血糖监测仪已被证明具有显著的治疗优势，但目前的酶传感器技术在临床上的应用有限，可能不足以进行闭环控制。GluMetrics建议开发一种新的、更准确的基于非酶的葡萄糖传感器，能够在整个生理范围(40至400 mg/dL)，特别是在低血糖范围(&lt；70 mg/dL)实现高水平的临床准确性。

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).