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：
8326165
负责人：
STUART ALAN WEINZIMER
金额：
$ 66.77万
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/8326165
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) 治疗方面的技术进步，包括胰岛素类似物、胰岛素泵疗法以及最近的连续血糖监测，仍然不足以使大多数 T1D 患者的血糖水平正常化。很可能没有手动的“开环”治疗性胰岛素方案能够最佳地控制 T1D 患者的血糖，并且生物胰岛细胞替代目前还不可行。 “闭环”自动化人工胰腺系统，包括精确输送可变量胰岛素的胰岛素泵、精确确定血糖水平的连续葡萄糖传感器以及根据实时血糖读数确定胰岛素输送速率的有效算法，仍然是减少高血糖和低血糖暴露的最有希望的干预措施。针对成人和青少年的短期医院研究已经证明了这种方法的可行性。然而，当前闭环方法的缺陷已经变得明显。目前的皮下胰岛素输送方法还不够快，不足以防止与膳食相关的血糖水平升高，并且血浆胰岛素水平持续升高与随后发生低血糖的风险相关。最重要的是，住院研究无法真实地复制通常家庭环境中固有的膳食和活动的变化。该研究项目的目标有两个：（1）使用加速皮下胰岛素输送或延迟碳水化合物吸收的策略来优化闭环系统的性能，从而改善餐时血糖控制并可能限制低血糖； (2) 使用逐步增加远程计算机化和无线通信技术的利用率并减少对传统受试者监测方法的依赖的逐步方法来评估流动环境中闭环输送的安全性和有效性。计划中的实验将建立在我们在胰岛素药代动力学、药效学和葡萄糖反调节方面的专业知识的基础上，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，并且可能不仅会增进我们对 T1D 闭环控制的理解，而且可能会增进我们对它作为无意识低血糖治疗的潜在用途的理解。公众健康相关性：对于大约七百分之一的美国人来说，推荐的强化治疗是困难的、繁重的，而且常常不足以预防长期并发症和发病率。开发能够有效调节血糖水平的自动反馈、葡萄糖控制、胰岛素输送系统将改善患者的治疗结果和生活质量，并有可能降低社会医疗保健成本。