Closed-Loop Effectiveness and Ambulatory Regimens (CLEAR)

闭环有效性和动态治疗方案 (CLEAR)

基本信息

批准号：
8142014
负责人：
STUART ALAN WEINZIMER
金额：
$ 67.56万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8142014
关键词：
Adolescent Adult Algorithms American Appearance Area Under Curve Artificial Pancreas Automation Beta Cell Biological Blood Circulation Blood Glucose Blood flow Bolus Infusion Car Phone Carbohydrates Child Childhood Clinical Communication Computer software Data Data Set Development Devices Diabetes Mellitus Drug Kinetics Eating Effectiveness Engineering Ensure Environment Euglycemic Clamping Event Exercise External Infusion Pumps Failure Feasibility Studies Feedback Fright Gastroparesis Glucagon Glucose Glucose Clamp Glycosylated hemoglobin A Goals Grant Health Health Care Costs Health Personnel Heating Home environment Hormonal Hormones Hospitals Hour Hybrids Hyperglycemia Hyperinsulinism Hypoglycemia Incidence Industry Collaboration Infusion procedures Inpatients Insulin Insulin Infusion Systems Insulin, Lispro, Human Insulin-Dependent Diabetes Mellitus Internet Intervention Islet Cell Kinetics Lead Link Manuals Massage Medical Surveillance Methods Modeling Modification Monitor Morbidity - disease rate Nature Normal Range Outcome Outpatients Parents Pathway interactions Patients Performance Personal Computers Pharmacodynamics Phase Physiological Pilot Projects Plasma Pramlintide Protocols documentation Pump Quality of life Reading Recurrence Regimen Regulation Reliance Research Research Design Research Personnel Research Project Grants Risk Route Running Safety Scientist Series Serious Adverse Event Simulate Site Skin Skin Temperature Sleep Subcutaneous Injections Supervision System Techniques Technology Telemetry Testing Therapeutic Time United States Food and Drug Administration Wireless Technology absorption analog base blood glucose regulation compare effectiveness computerized design experience glucagon-like peptide glucose monitor glucose sensor glycemic control head-to-head comparison hypoglycemia unawareness improved in vivo insight interstitial new technology next generation novel pharmacokinetic model prevent research study response safety net sensor subcutaneous success transmission process

项目摘要

DESCRIPTION (provided by applicant): Technological Improvements in the management of type 1 diabetes (T1D), including insulin analogs, insulin pump therapy, and most recently, continuous glucose monitoring, are still not sufficient to normalize glucose levels in most people with T1D. It is likely that no manual, "open-loop" therapeutic insulin regimen will be able to optimally control glycemia in patients with T1D, and biological islet-cell replacement is presently unfeasible. "Closed-loop" automated artificial pancreas systems, consisting of an insulin pump to precisely deliver variable amounts of insulin, a continuous glucose sensor to accurately determine the glucose levels, and effective algorithms to determine insulin delivery rates based on real-time glucose readings, remains the most promising intervention to reduce hyperglycemic and hypoglycemic exposures. Short-duration hospital-based studies in adults and adolescents have demonstrated feasibility of this approach. However, deficiencies in current closed-loop approaches have become apparent. Present methods of subcutaneous insulin delivery are not sufficiently rapid to prevent meal-related increases in blood glucose levels, and persistent elevations in plasma insulin levels are associated with a risk of subsequent hypoglycemia. Most importantly, inpatient studies cannot realistically replicate the variability of meals and activities inherent in the usual home environment. The objectives of this research project are twofold: (1) to optimize the performance of closed-loop systems using strategies to either accelerate subcutaneous insulin delivery or delay carbohydrate absorption, thereby allowing improved prandial glucose control and potentially limiting hypoglycemia; and (2) to evaluate the safety and effectiveness of closed-loop delivery in the ambulatory environment, using a stepwise approach that gradually increases utilization of remote computerized and wireless communication techniques and decreases reliance on traditional methods of subject monitoring. The planned experiments will build on our expertise in insulin pharmacokinetics and pharmacodynamics and glucose counter-regulation and benefit from our ongoing industry collaborations. The proposed studies are novel, important, and likely to advance our understanding not only of closed-loop control of T1D, but also its potential use as a treatment for hypoglycemia unawareness. PUBLIC HEALTH RELEVANCE: For the approximately 1 in 700 Americans with type 1 diabetes, recommended intensive treatments are difficult, burdensome, and frequently insufficient to prevent long-term complications and morbidity. Development of automated feedback, glucose-controlled, insulin delivery systems that would effectively regulate blood sugar levels would lead to improvements in patient outcomes and quality of life, and potentially, reduction in societal health care costs.

描述（由申请人提供）：1型糖尿病（T1D）管理的技术改进，包括胰岛素类似物，胰岛素泵治疗以及最近的连续葡萄糖监测，仍然不足以使大多数T1D患者的葡萄糖水平正常化。可能没有手动“开环”治疗性胰岛素治疗方案能够最佳地控制T1D患者的糖血症，并且生物学胰岛细胞替代目前是不可行的。 “闭环”自动人工胰腺系统，该系统由胰岛素泵组成，可精确提供可变量的胰岛素，一种连续的葡萄糖传感器，以准确确定葡萄糖水平，以及有效的算法，以确定基于实时葡萄糖读数的胰岛素递送速度，仍然是实时葡萄糖读取，仍然是最有可能的启发性的expoce expoce expoce expecorection expecormectic expecemectection。在成人和青少年的基于医院的短期研究表明这种方法的可行性。但是，当前闭环方法中的缺陷已经显而易见。皮下胰岛素输送的当前方法不足以防止与进餐相关的血糖水平增加，并且血浆胰岛素水平的持续升高与随后患低血糖症的风险有关。最重要的是，住院研究无法现实地复制通常家庭环境中固有的餐食和活动的可变性。该研究项目的目标是双重的：（1）使用策略来优化闭环系统的性能，以加速皮下胰岛素递送或延迟碳水化合物的吸收，从而允许改善挥发性的葡萄糖控制并潜在地限制低血糖症；（2）使用逐步方法来评估闭环交付在门诊环境中的安全性和有效性，该方法逐渐增加了对远程计算机和无线通信技术的利用，并降低了对传统的受试者监测方法的依赖。计划的实验将基于我们在胰岛素药代动力学和药效学和葡萄糖反调节方面的专业知识，并受益于我们正在进行的行业合作。拟议的研究是新颖的，重要的，并且可能不仅可以促进我们对T1D闭环控制的理解，而且还可以用作低血糖的潜在用途。公共卫生相关性：对于有1型糖尿病的700名美国人中，大约有1个，建议的强化治疗困难，繁重，并且经常不足以防止长期并发症和发病率。开发自动反馈，葡萄糖控制的胰岛素输送系统，这些系统将有效调节血糖水平，将改善患者的结局和生活质量，并有可能降低社会保健成本。