Clinical Evaluation of a Long Term Implanted Glucose Sensor

描述(由申请人提供)：糖尿病是一个正在达到危机程度的主要医疗问题，迫切需要新的治疗方法。我们正在开发一种长期的血糖传感器，它带有电池供电的遥测功能，可以植入皮下组织。该传感器将在1型糖尿病的低血糖预警、胰岛素剂量和人工胰腺控制方面具有独特的应用。该传感器还可用于2型糖尿病的血糖监测、肥胖症的卡路里和活动管理，以及易感个体的2型糖尿病预防。长期植入式葡萄糖传感器的开发已经进行了几年。以前的研究集中在单个传感器组件的开发上，包括：固定化葡萄糖氧化酶和过氧化氢酶的稳定制备，具有可控渗透性的新型膜，电化学检测器，植入式电子学和遥测，信号处理方法，以及密封式植入体外壳。含有这些成分的传感器已经在体外进行了广泛的测试，并被证明是稳定的。传感器作为短期植入物在啮齿类动物身上进行了广泛的测试，以确定微血管灌流和传质阻力的影响，导致传感器设计上的微小调整。在这个项目的第一阶段，传感器和遥测系统在猪身上植入了12-18个月，结果表明传感器仍然保持响应并能够长期监测血糖。除了长期的动物性能评估外，适当的生物相容性和其他临床前测试也已经完成。在这个项目中，我们现在将仔细验证在两个小规模的先导性人体临床试验中可以获得可接受的传感器性能，并将制定患者友好的传感器操作说明，包括校准方法和间隔。还将对传感器精度、滞后和灵敏度稳定性进行详细评估，以确定该设备是否适合未来在闭环应用中使用。长期植入式葡萄糖传感器在糖尿病和肥胖症的治疗中具有重要的作用。我们正在开发的传感器经过了系统工程分析、广泛的短期动物试验和长期的动物植入研究。该项目包括在大规模临床试验中对传感器进行评估之前的必要的最后步骤。 与公共卫生相关：糖尿病是一个正在达到危机程度的主要医疗问题，迫切需要新的治疗方法。在长期的动物植入测试中，我们已经展示了一种新的葡萄糖传感器的操作，该传感器将在糖尿病的低血糖预警、胰岛素剂量和人工胰腺控制方面具有独特的应用。在这个第二阶段的项目中，我们建议对该传感器进行首次人类临床评估。

DESCRIPTION (provided by applicant): Diabetes is a major healthcare problem that is reaching crisis proportions, and new therapies are urgently needed. We are developing a long-term glucose sensor with battery-operated telemetry for implantation in subcutaneous tissues. The sensor would have unique applications in type 1 diabetes for hypoglycemia warning, insulin dosing, and control of the artificial pancreas. The sensor may also have application for glucose monitoring in type 2 diabetes, caloric and activity management in obesity, and prevention of type 2 diabetes in susceptible individuals. Development of the long-term implantable glucose sensor has been underway for several years. Previous studies have focused on the development of individual sensor components including: stable preparations of immobilized glucose oxidase and catalase, novel membranes with controlled permeability, electrochemical detectors, implantable electronics and telemetry, signal processing methods, and the hermetic implant housing. Sensors incorporating these components have been tested extensively in vitro and have proven stable. The sensors were tested extensively as short-term implants in rodents to determine the effects of micro-vascular perfusion and mass transfer resistance, leading to minor adjustments in sensor design. In Phase I of this project, the sensor and telemetry system were implanted for 12-18 months in pigs, and results demonstrated that the sensor remains responsive and capable of monitoring blood glucose for extended periods. In addition to the long-term animal performance evaluations, appropriate biocompatibility and other pre- clinical testing has also been completed. In this project, we will now carefully verify that acceptable sensor performance can be obtained in two small-scale pilot human clinical trials, and we will develop patient-friendly instructions for sensor operation, including calibration method and interval. Detailed assessments of sensor accuracy, lag, and sensitivity stability will also be conducted to determine suitability of the device for future use in closed-loop applications. The long-term implantable glucose sensor has an important role in the therapy for diabetes and obesity. The sensor we are developing has undergone systematic engineering analysis, extensive short-term animal tests, and long-term animal implant studies. This project comprises the necessary last steps prior to evaluation of the sensor in large-scale clinical trials. PUBLIC HEALTH RELEVANCE: Diabetes is a major healthcare problem that is reaching crisis proportions, and new therapies are urgently needed. In long-term animal implant tests, we have demonstrated operation of a new glucose sensor that would have unique applications in diabetes for hypoglycemia warning, insulin dosing, and control of the artificial pancreas. In this Phase II project we propose to perform the first human clinical evaluations of the sensor.