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

临床前验证

• 批准号: 7210766
• 负责人: Joseph Y. Lucisano
• 金额: $ 49.93万
• 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 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7210766
• 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。我们正在开发一种长期葡萄糖传感器的大小瓶盖与电池供电的遥测植入皮下组织。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。传感器已被广泛测试为短期植入啮齿动物，以确定微血管灌注和传质阻力的影响，导致传感器设计的微小调整。传感器和遥测系统也已在猪体内植入4-5个月，初步结果表明，传感器仍对葡萄糖有反应，尽管灵敏度可能受到异物反应的影响。 在开始长期人体研究之前，现在是确定作为动物植入物的最终传感器寿命和可靠性的时候了。传感器将植入猪体内长达18个月，并定期进行葡萄糖挑战。将定期对单个传感器进行测试，并进行广泛表征，以确定单个传感器组件的可靠性和预计寿命。将采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之前的最后障碍。 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初步的长期植入研究。该项目将通过猪的长期植入研究确定最终传感器寿命和可靠性，作为启动人体试验前的最后一步。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控制。在该I期项目中，我们计划在II期计划的人体临床评价之前完成剩余的几项任务。