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

 描述(申请人提供)：1型糖尿病的闭环控制模式：有效性和系统接受度2009年，我们发起了首批致力于1型糖尿病闭环控制(CLC)工程和临床测试的NIH研究之一。从那时起，我们取得了关键的里程碑和得出的结论，使我们能够在这个快速增长的领域进行进一步的研究。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，而是一个包含患者的数字治疗生态系统中的网络，可以根据患者的临床情况实时提供和改变不同的治疗方式 州政府。这一新概念体现在：(1)我们的CLC算法的模块化工程设计，现在可以不间断地启动和交换各种治疗方式；(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，专为患者设计，目前在美国和欧洲的许多门诊研究中使用 统一安全系统(USS弗吉尼亚号)-第一个CLC算法旨在调整其在每晚的运行模式，首先缓解餐后高血糖，然后将患者滑至120 mg/dl的目标晨间血糖，从而重新设置他/她新的一天的代谢状态。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模式的长期疗效-传感器增强泵(SAP)与USS+SAP白天(D)与USS+CLC(D)。我们计划将84名1型糖尿病患者随机分为两种不同的治疗顺序：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两个月--有足够的时间来实现以下具体目标：SA1：USS+SAP(D)在以下方面达到的隔夜CLC将优于单独使用SAP：(1)改善HbA1c而不增加低血糖风险；(2)降低一夜低血糖的发生率和风险，以及(3)减少对低血糖的恐惧，改善糖尿病生活质量评分。SA2：USS+CLC(D)在白天实现的CLC将保留USS+SAP(D)的好处，并将在以下方面优于USS+SAP(D)：(1)白天在70-180 mg/dl的目标范围内的时间增加；(2)降低运动中和运动后低血糖的风险，以及(3)减少餐后血糖变异性。 SA3：通过焦点小组访谈和技术接受分数评估的CLC系统接受度将是：(1)优，USS+SAP(D)与单独使用SAP相比，即一夜之间添加USS将提高患者对CLC的接受度；(2)与USS+SAP(D)相比，USS+CLC(D)略差；即，由于感觉到系统复杂性增加，一些患者在白天更喜欢单独使用SAP。总体而言，我们希望确定一种独特的夜间CLC模式(弗吉尼亚州号USS)与白天的SAP治疗相结合，是未来适应性治疗方案的可行先驱，实现了优于单独使用SAP的血糖控制，并在系统复杂性和预期益处之间实现了最佳平衡。

 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.