Pre-Clinical Validation & Ultimate Lifetime of Long Term Implanted Glucose Sensor

临床前验证

• 批准号: 7426437
• 负责人: Joseph Y. Lucisano
• 金额: $ 49.95万
• 依托单位: GLYSENS, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-01 至 2009-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7426437
• 关键词: Address; Affect; Agreement; Animal Testing; Animals; Applied Research; Artificial Pancreas; Award; Biocompatible Materials; Blood Glucose; Blood specimen; Caliber; Classification; Clinical; Clinical Research; Clinical Trials; Collaborations; Data Display; Development; Devices; Diabetes Mellitus; Diagnostic Procedure; Diagnostic tests; Dose; Electrodes; Electronics; Engineering; Enzyme Electrodes; Equipment; Evaluation; Failure; Family suidae; Foreign Bodies; Foundations; Funding; Glucose; Goals; Government; Grant; Hamsters; Healthcare; Heart Rate; Histologic; Housing; Human; Hypoglycemia; Image; Implant; In Vitro; Individual; Insulin; Insulin-Dependent Diabetes Mellitus; Laws; Life; Longitudinal Studies; Measurable; Measurement; Membrane; Methods; Minor; Modeling; Monitor; Nature; Non-Insulin-Dependent Diabetes Mellitus; Numbers; Obesity; Operative Surgical Procedures; Oxygen; Performance; Perfusion; Permeability; Personal Satisfaction; Phase; Pilot Projects; Population; Preparation; Process; Property; Protocols documentation; Rate; Research Design; Resistance; Rodent; Role; Series; Signal Transduction; Site; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Solid; Source; Standards of Weights and Measures; Sterilization for infection control; Structure; Subcutaneous Tissue; Sus scrofa; System; Telemetry; Temperature; Testing; Time; Tissue Sample; Tissues; Toxic effect; Toxicology; United States Food and Drug Administration; United States National Institutes of Health; Universities; Validation; Wireless Technology; Work; base; biomaterial compatibility; blood glucose regulation; catalase; computerized data processing; design; detector; diabetes mellitus therapy; engineering design; glucose monitor; glucose oxidase; glucose sensor; human study; implantable device; implantation; implanted sensor; improved; instrumentation; novel; obesity prevention; pre-clinical; programs; research clinical testing; research study; response; sensor; size; subcutaneous; success; telemetering

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 the size of a bottle cap 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 immobilzed 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 have been tested extensively as short-term implants in rodents to determine the effects of microvascular perfusion and mass transfer resistance, leading to minor adjustments in sensor design. The sensor and telemetry system have also been implanted for 4-5 months in pigs, and preliminary results demonstrate that the sensor remains responsive to glucose, although the sensitivity can be affected by the foreign body response. It is now time to determine the ultimate sensor lifetime and reliability as an implant in animals before initiating long-term human studies. Sensors will be implanted in pigs for up to 18 months and regular glucose challenges will be performed. Individual sensors will be explanted at regular intervals and characterized extensively to determine the reliability and projected lifetime of individual sensor components. Tissue samples will be collected for extensive histologic analysis. This study will address the last hurdles before human trials. 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 preliminary long-term implant studies. This project will establish the ultimate sensor lifetime and reliability by long-term implant studies in pigs, as the last step before initiating human trials. 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 type 1 diabetes for hypoglycemia warning, insulin dosing, and control of the artificial pancreas. In this Phase I project we propose to complete the few remaining tasks required prior to human clinical evaluation, which is planned for Phase II.

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，它有瓶盖大小，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。传感器已经作为短期植入物在啮齿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。传感器和遥测系统也已经在猪身上植入了4-5个月，初步结果表明，传感器仍然对葡萄糖有反应，尽管敏感性可能会受到异物反应的影响。 在启动长期的人体研究之前，现在是时候确定作为植入动物的最终传感器的寿命和可靠性了。传感器将被植入猪体内长达18个月，并将进行常规的血糖挑战。将定期对单个传感器进行移植，并对其进行广泛的表征，以确定单个传感器组件的可靠性和预计寿命。将收集组织样本进行广泛的组织学分析。这项研究将解决人体试验前的最后一个障碍。 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初步的长期植入研究。该项目将通过在猪身上进行长期植入研究，作为启动人体试验之前的最后一步，建立最终的传感器寿命和可靠性。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。在这个第一阶段项目中，我们建议完成人体临床评估之前所需的少数剩余任务，这是计划在第二阶段进行的。