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.

摘要 意义：美国有500多万接受胰岛素治疗的糖尿病患者 在可归因于糖尿病的2370亿美元直接医疗费用中，这一比例高得不成比例。对.的使用 连续血糖监测(CGM)已被证明可以降低HbA1c水平，而HbA1c已被证明是健康的预测指标 在这一人群中的结果，当CGM与CGM相结合时取得了最大的改善 持续皮下胰岛素输注(CSII)。最近CGM和胰岛素泵的融合已经 启用了第一代自动胰岛素递送(AID)系统，承诺会有更好的血糖 胰岛素治疗糖尿病的对照。然而，当前的AID系统复杂、笨重且昂贵 因为他们需要在身体上佩戴多种设备：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，它可以减少 皮下组件的数量从2个减少到1个，显著降低了这些组件的大小和复杂性 系统。我们计划在这一领域商业化的PDT可互操作传感插管组件 第二阶段SBIR将允许任何胰岛素补丁泵制造商快速将CGM直接集成到胰岛素上 输送套管，从而使使用补丁泵的T1D患者能够轻松地使用CGM 通过单一的皮下注射部位。重要的是，该平台还将提高AID系统的可靠性 通过将CGM到泵控制器的无线通信替换为直接有线 联系。由此带来的系统规模、复杂性和成本的降低将提高泵的采用率 使用AID的用户和人员，帮助提高合规性、降低HbA1c水平并改善健康结果 在1型糖尿病患者中。初步数据：PDT最近证明，传递胰岛素 在葡萄糖检测部位，可以使用一种基于氧化还原介体的专利传感插管。然而， 我们还表明，在注射一定剂量的胰岛素后，会立即出现稀释伪影。 通过插管。我们已经证明，这种伪影与胰岛素或生理盐水的输送无关。 在这项SBIR的第一阶段中，我们在一项猪研究中证明了这种伪影与团注的大小有关。 我们进一步证明，通过使用更高浓度的胰岛素和 最终通过使用复杂的预测信号处理方法消除。具体目标：在第二阶段 在这个项目中，我们将使用第一阶段的产品来采取下一个合乎逻辑的步骤来整合我们的传感 将套管送入双功能贴片泵平台。在具体目标1中，我们将进一步描述和评估 在一项人体研究中，光动力疗法传感套管的准确性。在《特定目标2》中，我们将与一则商业广告合作 泵合作伙伴(EOFlow)开发和评估可互操作的传感套管组件(ISCA) 专为快速集成到补丁泵而设计。ISCA将包括所需的电子、机械 组件和软件开发工具包，可以快速集成到商业补丁泵中。 与我们在OHSU的学术伙伴合作，我们将传递人工产物消除预测信号 处理算法，并将该算法移植到ISCA中用于实时操作。在具体目标3中，我们 将传感器组件集成到我们的商业合作伙伴的补丁泵中，并验证其性能和 猪研究中设计的准确性。在第二阶段结束时，我们将有一个双重功能的葡萄糖- 传感补丁泵在猪的研究中得到了验证，并准备进入临床研究。在2B阶段，我们将进行 并与我们的学术合作者和商业化合作伙伴合作，将 将模型预测控制器集成到贴片泵中，以产生一体式自动胰岛素给药解决方案。