Clinical Evaluation of a Long Term Implanted Glucose Sensor

描述（由申请人提供）：糖尿病是一个主要的医疗保健问题，正在达到危机的比例，迫切需要新的治疗方法。我们正在开发一种长期葡萄糖传感器，具有电池供电的遥测功能，可植入皮下组织。该传感器将在1型糖尿病中具有独特的应用，用于低血糖警告，胰岛素剂量和人工胰腺的控制。该传感器还可以应用于2型糖尿病的葡萄糖监测、肥胖症的热量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。以前的研究主要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剂，具有受控渗透性的新型膜，电化学检测器，植入式电子设备和遥测，信号处理方法和密封植入外壳。包含这些组件的传感器已在体外进行了广泛测试，并已证明稳定。传感器作为短期植入物在啮齿动物中进行了广泛测试，以确定微血管灌注和传质阻力的影响，从而对传感器设计进行了微小调整。在该项目的第一阶段，传感器和遥测系统在猪体内植入12-18个月，结果表明传感器保持响应，能够长时间监测血糖。除长期动物性能评价外，还完成了适当的生物相容性和其他临床前试验。在这个项目中，我们将仔细验证在两个小规模的试点人体临床试验中可以获得可接受的传感器性能，我们将为传感器操作开发患者友好的说明，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，以确定该设备未来在闭环应用中的适用性。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作用。我们正在开发的传感器经过了系统的工程分析、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评估传感器之前的必要最后步骤。 公共卫生相关性：糖尿病是一个主要的医疗保健问题，正在达到危机的程度，迫切需要新的治疗方法。在长期动物植入试验中，我们已经证明了一种新型葡萄糖传感器的操作，该传感器在糖尿病中具有独特的应用，用于低血糖警告、胰岛素剂量和人工胰腺控制。在该II期项目中，我们计划对传感器进行首次人体临床评价。

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.