Development of a miniaturized single-port automated insulin delivery system utilizing a glucose sensing catheter, ultra-concentrated insulin, and an optimized control algorithm

利用葡萄糖传感导管、超浓缩胰岛素和优化控制算法开发小型化单端口自动胰岛素输送系统

• 批准号: 10452613
• 负责人: Thomas Ludwig Seidl
• 金额: $ 55.24万
• 依托单位: PACIFIC DIABETES TECHNOLOGIES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-20 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10452613
• 关键词: Adoption; Algorithms; Ambulatory Care Facilities; Blood Glucose; Blood Glucose Self-Monitoring; Bolus Infusion; Calibration; Cannulas; Catheters; Clinic; Clinical Research; Communication; Complex; Coupled; Data; Development; Devices; Diabetes Mellitus; Dose; Electronics; Family suidae; Generations; Glucose; Glucose Clamp; Glycosylated hemoglobin A; Health; Housing; Human; Hyperglycemia; Infusion procedures; Insulin; Insulin Infusion Systems; Insulin-Dependent Diabetes Mellitus; Legal patent; Libraries; Liquid substance; Manufacturer Name; Measurement; Measures; Mechanics; Mediator of activation protein; Medical Care Costs; Methodology; Methods; Miniature Swine; Morphologic artifacts; Outcome; Outcome Measure; Outpatients; Oxidation-Reduction; Participant; Partner in relationship; Patients; Performance; Persons; Phase; Population; Pump; Reading; Saline; Sampling; Secure; Security; Series; Site; Small Business Innovation Research Grant; Subcutaneous Injections; System; Testing; Time; United States; Work; base; blood glucose regulation; commercialization; cost; design; diabetes management; digital; efficacy evaluation; glucose monitor; glucose sensor; glycemic control; human study; improved; interoperability; miniaturize; operation; predictive modeling; primary outcome; prospective; recruit; research clinical testing; secondary outcome; sensor; signal processing; software development; subcutaneous; success; tool; usability; wireless communication

ABSTRACT Significance: There are over 5 million people with insulin-treated diabetes in the United States who represent a disproportionately large share of the $237B in direct medical costs attributable to diabetes. The use of continuous glucose monitoring (CGM) has been shown to reduce HbA1c levels, a proven predictor of health outcomes within this population, with the greatest improvement achieved when CGM is coupled with continuous subcutaneous insulin infusion (CSII). The recent convergence of CGM and insulin pumps has enabled the first generation of automated insulin delivery (AID) systems, promising even better glycemic control for insulin-treated diabetes. However, current AID systems are complex, cumbersome, and expensive for the patient because they require multiple devices to be worn on the body: a glucose sensor, an insulin pump, and an insulin delivery catheter. We have developed a glucose sensing catheter that reduces the number of subcutaneous components from two to one, significantly reducing the size and complexity of these systems. The PDT interoperable sensing cannula assembly that we are proposing to commercialize in this phase 2 SBIR will allow any insulin patch pump manufacturer to rapidly integrate CGM directly on the insulin delivery cannula, thereby enabling people with T1D who are patch pump users to effortlessly utilize CGM through a single subcutaneous injection site. Importantly, this platform will also improve AID system reliability and security by replacing the wireless communication from CGM to pump controller with a direct wired connection. Resulting reductions in system size, complexity, and cost will increase adoption rates for pump user and people using AID, helping improve compliance, lower HbA1c levels, and improve health outcomes among people with type 1 diabetes. Preliminary Data: PDT has recently demonstrated that delivering insulin at the site of glucose sensing is possible using a patented redox mediator-based sensing cannula. However, we have also shown that there is a dilution artifact that occurs immediately after a dose of insulin is delivered through the cannula. We have shown that this artifact is independent of whether insulin or saline is delivered. In Phase 1 of this SBIR, we demonstrated in a swine study that this artifact is related to the size of the bolus. We further demonstrated that the artifact can be significantly reduced by using higher concentration insulin and ultimately eliminated by using sophisticated predictive signal processing methods. Specific Aims: In Phase 2 of this project, we will use the products of Phase 1 to take the next logical steps in integration of our sensing cannula into a dual function patch pump platform. In Specific Aim 1, we will further characterize and evaluate the accuracy of the PDT sensing cannula in a human study. In Specific Aim 2, we will work with a commercial pump partner (EOFlow) to develop and evaluate an interoperable sensing cannula assembly (ISCA) that is designed for rapid integration into a patch pump. The ISCA will include the required electronics, mechanical components, and a software development kit that will enable rapid integration into commercial patch pumps. Working with our academic partners at OHSU, we will transfer the artifact elimination predictive signal processing algorithm and port this algorithm to the ISCA for use in real-time operation. In Specific Aim 3, we will integrate the sensor assembly into our commercial partner’s patch pump and validate the performance and accuracy of the design in a swine study. At the conclusion of Phase 2, we will have a dual-function glucose- sensing patch pump validated in a swine study and poised to enter clinical study. In Phase 2B, we will conduct those studies, and work with our academic collaborators and commercialization partners to incorporate a model predictive controller into the patch pump to yield an all-in-one automated insulin delivery solution.

抽象的 意义：美国代表的500万人患有胰岛素治疗的糖尿病 在237B $ 237B的直接医疗费用中，造成糖尿病的直接医疗费用的份额不成比例。使用 连续葡萄糖监测（CGM）已显示可降低HBA1C水平，这是健康的预测指标 该人群中的结果，当CGM与 连续皮下胰岛素输注（CSII）。 CGM和胰岛素泵最近的收敛性具有 启用了第一代自动胰岛素输送（AID）系统，有望更好地血糖 控制胰岛素治疗的糖尿病。但是，当前的援助系统很复杂，繁琐且昂贵 对于患者，因为他们需要多个设备戴在体内：葡萄糖传感器，胰岛素 泵和胰岛素输送导管。我们已经开发了一种葡萄糖传感导管，可减少 皮下组件的数量从两个到一个，大大降低了这些成分的大小和复杂性 系统。我们建议在此商业化的PDT互操作感应插管组件 第2阶段SBIR将允许任何胰岛素补丁泵制造商直接在胰岛素上迅速整合CGM 送货套管，从而使具有T1D的人是补丁泵用户，可以毫不费力地利用CGM 通过一个皮下注射部位。重要的是，该平台还将提高援助系统的可靠性 通过直接有线替换从CGM到泵控制器的无线通信，通过 联系。导致系统尺寸，复杂性和成本的降低将提高泵的采用率 用户和使用援助的人，有助于提高合规性，降低HBA1C水平并改善健康状况 在1型糖尿病的人中。初步数据：PDT最近证明了提供胰岛素 使用基于氧化还原介质的感应套管，可以在葡萄糖传感的位置传感。然而， 我们还表明，在输送一剂胰岛素后立即发生稀释伪像 通过套管。我们已经表明，该工件独立于胰岛素或盐水是否已输送。 在该SBIR的第1阶段中，我们在一项猪研究中证明了该伪影与推注的大小有关。 我们进一步证明，通过使用较高浓度胰岛素和 最终通过使用复杂的预测信号处理方法消除。具体目的：在第2阶段 在该项目中，我们将使用第1阶段的产品来采取下一个逻辑步骤，以整合我们的敏感性 套管进入双功能补丁泵平台。在特定目标1中，我们将进一步表征和评估 在人类研究中，PDT传感套管的准确性。在特定目标2中，我们将与广告合作 泵合作伙伴（eoflow）开发和评估可互操作的感应套管组件（ISCA） 设计用于快速集成到补丁泵中。 ISCA将包括所需的电子设备，机械 组件和软件开发套件将使可以快速集成到商业补丁泵中。 与我们在OHSU的学术合作伙伴一起工作，我们将转移消除工件的预测信号 处理算法并将此算法移植到用于实时操作的ISCA。在特定的目标3中，我们 将将传感器组件集成到我们的商业合作伙伴的补丁泵中，并验证性能和 猪研究中设计的准确性。在第2阶段结束时，我们将具有双功能葡萄糖 - 在一项猪研究中验证的贴片泵，并中毒以进入临床研究。在2B阶段，我们将进行 这些研究，并与我们的学术合作者和商业化合作伙伴合作，以结合 将预测控制器模拟到斑块泵中，以产生多合一的自动胰岛素输送解决方案。