Closed-Loop Control Modalities in Type 1 Diabetes: Efficacy and System Acceptance

 描述（由申请人提供）：1型糖尿病的闭环控制模式：有效性和系统验收2009年，我们启动了第一个NIH研究，致力于1型糖尿病闭环控制（CLC）的工程和临床试验。从那时起，我们已经取得了关键的里程碑和得出的结论，使进一步研究在这个快速增长的领域。值得注意的是，我们提出了这样的想法，即人工胰腺不是一个单一的一体化设备，而是一个在数字治疗生态系统中包含患者的网络，该网络可以根据患者的临床表现在真实的时间内提供和改变不同的治疗方式。 状态这一新的概念体现在：（1）我们的CLC算法的模块化工程设计，现在允许各种治疗模式的启动和交换没有中断;（2）糖尿病助手（DiAs）-第一个使用智能手机运行控制算法的便携式CLC中心，专门设计由患者操作，目前在美国和欧洲的一些门诊研究中使用，以及（3） 统一安全系统（USS Virginia）-第一个CLC算法，设计用于在每晚的过程中调整其操作模式，首先缓解餐后高血糖，然后将患者的目标早晨血糖降至120 mg/dl，从而重置他/她的代谢状态以迎接新的一天。使用这些技术，我们现在建议在一项随机交叉试验中比较三种治疗方式的长期疗效-传感器增强泵（SAP）与USS+SAP白天（d）与USS+CLC（d）。我们计划将84例1型糖尿病患者随机分为两种不同的治疗序列：SAP、USS+SAP（d）、USS+CLC（d）、USS+SAP（d）和USS+SAP（d）、USS+CLC（d）、USS+SAP（d）、SAP。每种治疗方式将持续2个月-有足够的时间来实现以下特定目标：SA 1：USS+SAP（d）实现的隔夜CLC在以下方面上级单独的SAP：（1）改善HbA 1c，而不增加低血糖风险;（2）降低隔夜低血糖的发生率和风险，以及（3）降低对低血糖的恐惧并改善糖尿病生活质量评分。SA2：通过USS+CLC（d）实现的白天CLC将保留USS+SAP（d）的益处，并且在以下方面上级USS+SAP（d）：（1）白天在70- 180 mg/dl目标范围内的时间增加;（2）运动期间和运动后低血糖风险降低;（3）餐后血糖变异性降低。 SA3：通过焦点小组访谈和技术接受度评分评估的CLC系统接受度将为：（1）与单独使用SAP相比，USS+SAP（d）的接受度为上级，即添加USS过夜将增加患者对CLC的接受度，以及（2）与USS+SAP（d）相比，USS+CLC（d）的接受度略差;即，由于感觉到系统复杂性增加，一些患者更喜欢白天单独使用SAP。总体而言，我们期望建立一个独特的夜间CLC模式（USS弗吉尼亚）结合SAP治疗在白天是一个可行的先驱，未来适应性治疗方案，实现血糖控制是上级SAP单独和系统复杂性和感知的好处之间的最佳平衡。

 DESCRIPTION (provided by applicant): Closed-Loop Control Modalities in Type 1 Diabetes: Efficacy and System Acceptance In 2009 we initiated one of the first NIH studies dedicated to engineering and clinical testing of closed-loop control (CLC) of type 1 diabetes. Since then, we have achieved key milestones and derived conclusions which enabled further research in this rapidly growing field. Notably, we proposed the idea that the artificial pancreas is not a single all-in-one device but a network encompassing the patient in a digital treatment ecosystem that can offer and alter different treatment modalities in real time depending on the patient's clinical state. This new notion was reflected in: (1) Our modular engineering design of CLC algorithms, which now allows various treatment modalities to be initiated and swapped without interruption; (2) The Diabetes Assistant (DiAs) - the first portable CLC hub using a smart phone to run control algorithms and specifically designed to be operated by the patient, which is now used in a number of outpatient studies in the U.S. and in Europe, and (3) The Unified Safety System (USS Virginia) - the first CLC algorithm engineered to adapt its mode of operation during the course of every night, first mitigating after-dinner hyperglycemia and then sliding the patient to a target morning glucose of 120mg/dl, thereby resetting his/her metabolic state for a new day. Using these technologies, we now propose to compare in a randomized cross-over trial the long-term efficacy of three treatment modalities - sensor-augmented pump (SAP) vs. USS+SAP during the day(d) vs. USS+CLC(d). We plan to randomize 84 patients with type 1 diabetes into two different treatment sequences: SAP,USS+SAP(d),USS+CLC(d),USS+SAP(d) and USS+SAP(d),USS+CLC(d),USS+SAP(d),SAP. Each treatment modality will continue for 2 months - sufficient time to address the following specific aims: SA1: Overnight CLC achieved by USS+SAP(d) will be superior to SAP alone in terms of: (1) Improved HbA1c without increasing the risk for hypoglycemia; (2) Reduced incidence and risk for hypoglycemia overnight, and (3) Reduced fear of hypoglycemia and improved diabetes quality of life scores. SA2: CLC during the day achieved by USS+CLC(d) will preserve the benefits of USS+SAP(d) and will be superior to USS+SAP(d) in terms of: (1) Increased time within target range of 70-180mg/dl during the day; (2) Reduced risk for hypoglycemia during and after exercise, and (3) Reduced postprandial glucose variability. SA3: CLC system acceptance evaluated by focus-group interviews and technology acceptance scores will be: (1) Superior, for USS+SAP(d) compared to SAP alone, i.e. adding USS overnight will increase patients' acceptance of CLC, and (2) Marginally inferior, for USS+CLC(d) compared to USS+SAP(d); i.e. some patients would prefer SAP alone during the day due to perceived increased system complexity. Overall, we expect to establish that a distinct overnight CLC modality (USS Virginia) combined with SAP therapy during the day is a viable precursor to future adaptable therapeutic schemes, achieving glycemic control that is superior to SAP alone and optimal balance between system complexity and perceived benefits.