Network Control of Diabetes: Aligning Artificial Pancreas Design with Physiology

描述（由申请人提供）：该项目是来自弗吉尼亚大学（UVA）和斯坦福大学的医生、数学家和工程师的跨学科和跨机构努力，致力于开发和测试一种新的网络控制人工胰腺（AP）概念：通过在模块化设计中将工程控制功能与生理和行为过程对准来优化1型糖尿病的治疗。将这一概念应用于临床实践的工具将是糖尿病助手（DiAs）--全球首个用于门诊闭环控制（CLC）试验的智能手机AP系统。DiAs结合了本地患者服务（例如低血糖预防、建议、CLC）和全球服务（例如实时远程监控、远程医疗）。系统开发将利用15年的广泛理论工作，CLC研究，行为干预和尖端工程设计。然而，我们的基本理念是简单明了的：为了取得成功，CLC需要包括一个强大的安全系统，以降低低血糖的风险，并从每个人的日常行为和基础/餐时模式中学习控制算法。(1)技术开发将包括：（i）基于我们的原型医疗Android操作系统的结构软件设计（存放在FDA主文件2109中），并添加系统管理程序，以实现关键CLC功能与其他非关键流程的无缝协同执行（例如，正常的智能手机操作）;（ii）通过结合特定于预防低血糖的模块，将咨询和CLC算法与关键生理过程对齐，基础/餐时曲线的行为优化，以反映每个患者的日常模式;以及胰岛素输送的实时微调，以安全地强化治疗。(2)临床试验将包括：（i）研究1证明了CLC对低血糖无意识的逆转，这将是使用我们的低血糖预防统一安全系统（USS Virginia）1个月的结果;（ii）研究2部署了由本地和全球咨询模块组成的咨询系统，该系统将通过将每个人的每日基础/餐时曲线与个人行为模式相匹配来优化每个人的每日基础/餐时曲线。(iii)研究3将安全、咨询和CLC模块整合到一个综合网络控制系统中。具体而言：USS将防止低血糖-最佳糖尿病控制的主要障碍-从而允许通过全整合CLC强化治疗，该CLC将调整胰岛素输送以微调每个人的行为优化配置文件。DiAs技术将主要由UVA团队开发。所有临床研究将在 在UVA（侧重于成人患者）和斯坦福大学（侧重于儿科人群）进行平行研究。最终，该项目将最终确定并广泛测试模块化便携式AP系统，使其 准备临床部署。

DESCRIPTION (provided by applicant): This project is an interdisciplinary and inter-institutional effort of physicians, mathematicians, and engineers from the University of Virginia (UVA) and Stanford University, dedicated to development and testing of a new network-control artificial pancreas (AP) concept: optimization of glycemia in type 1 diabetes by alignment of engineering control functions with physiologic and behavioral processes in a modular design. The vehicle for implementation of this concept into the clinical practice will be the Diabetes Assistant (DiAs) - the first [worldwide] smart-phone AP system used in outpatient closed-loop control (CLC) trials. DiAs combines local patient services (e.g. hypoglycemia prevention, advice, CLC), and global services (e.g. real-time remote monitoring, telemedicine). The system development will utilize 15 years of extensive theoretical work, CLC studies, behavioral interventions, and cutting-edge engineering designs. Nevertheless, our basic philosophy is straightforward: in order to be successful, CLC needs to include a robust safety system reducing the risk for hypoglycemia and control algorithms learning from each individual's daily behavioral and basal/bolus patterns. (1) Technology development will include: (i) Structural Software design, based on our prototype Medical Android operating system (deposited in FDA Master File 2109), and adding a system hypervisor to enable seamless co-execution of critical CLC functions together with other non-critical processes (e.g. normal smart phone operation); (ii) Alignment of Advisory and CLC Algorithms with key physiological processes by incorporating modules specific to prevention of hypoglycemia, behavioral optimization of basal/bolus profiles to reflect each patient's daily patterns; and real-time fine-tuning of insulin delivery to safely intensify treatment. (2) Clinical Trials will include: (i) Study 1 demonstrating reversal of hypoglycemia unawareness with CLC, which will result from 1-month use of our hypoglycemia-preventing Unified Safety System (USS Virginia); (ii) Study 2 deploying an Advisory System comprised of local and global advisory modules, which will optimize each person's daily basal/bolus profiles by matching them to individual behavioral patterns. (iii) Study 3 bringing together Safety, Advisory, and CLC modules into a comprehensive network-control system. Specifically: the USS will safeguard against hypoglycemia - the primary barrier to optimal diabetes control - thereby allowing intensified treatment by Fully-Integrated CLC, which will adjust insulin delivery to fine-tune each person's behaviorally-optimized profile. The DiAs technology will be primarily developed by the UVA team. All clinical studies will be carried out in parallel at UVA (focusing on adult patients) and Stanford (focusing on pediatric population). Ultimately, this project will finalize and test extensively a modular portable AP system, making it ready for clinical deployment.