Translation of the UVA Advanced Automated Insulin Delivery Systems to Clinical Care in Young Children: Glycemic Control, Regulatory Acceptance and Optimization of Day to Day Use

2011年，我们提出了人工胰腺（AP）系统是一个数字治疗生态系统的想法， 根据患者/家庭的偏好和信号可用性提供不同的治疗方式。经过广泛 经过全球范围的测试，我们的CLC算法和AP组件已在商业系统中实现 （Dexcom，前身为TypeZero、InControl和Tandem t：带ControlIQ的slim X2） 经过30多项临床试验和120万小时的使用，2019年获得了最佳结果。我们现在建议，与 Tandem Diabetes Care和Dexcom，推出下一代算法技术胰岛素泵， 连续葡萄糖传感器。使系统更小巧、易于使用，并具有完美的用户界面 2-6岁儿童及其父母/照顾者。在这一点上，我们可以确认，可靠的技术已经 已经开发并积累了足够的数据，以保证进行大规模的研究，旨在建立 这种新的最先进的技术作为临床上可接受的治疗儿童（2-6岁）1型 糖尿病（T1 D）及其家人。我们建议在3个研究中心进行一项大规模的多中心临床试验， 美国将招募102名2-6岁的T1 D儿童及其至少1名父母/照顾者， 在一项2：1随机对照平行研究中使用该系统3个月，比较AP与标准治疗 （SoC）。此外，研究将延长3个月，SoC组将过渡到使用 AP和实验组将继续进行更轻松的随访。所有研究中心均为儿科 在儿童临床试验和AP跟踪记录方面具有广泛专业知识的中心。我们将展示： (1)CLC实现的血糖控制在以下方面上级SoC治疗：（i）降低 低血糖而不恶化的HbA 1c;（ii）改善70-180 mg/dl的目标范围内的时间， （iii）改善HbA 1c而不增加低血糖风险，特别是对于 基线时HbA 1c <7.5%的患者，以及（iv）低于54 mg/dl和高于54 mg/dl的极端血糖事件减少 300 mg/dl，以及更少的严重低血糖发作、DKA发作或其他严重不良事件。 (2)使用具有实时监控和云功能的AP将减少糖尿病患者的痛苦， 在：（i）减少父母和孩子对低血糖的恐惧，提高父母/照顾者的生活质量 （ii）系统接受度和对AP用户界面的积极评价， 即时遥距监察/自动通知系统;后者对家长特别有用 当儿童在学前/日托时，以及（iii）系统可靠性和可用性满足监管验收要求 的搜索. 因此，我们希望测试和验证AP系统，包括交互本地（AP，靠近孩子）和 全局（云/实时远程监控，可供家长使用）组件，共同提供 为2-6岁的1型糖尿病儿童提供最佳的血糖控制，让他们的家人安心。

In 2011 we put forward the idea that Artificial Pancreas (AP) systems is a digital treatment ecosystem that can offer different treatment modalities tailored to patient/families' preferences and signal availability. After extensive testing around the world, our CLC algorithm and AP components were implemented in commercial systems (Dexcom, formerly TypeZero, InControl and Tandem t:slim X2 with ControlIQ) available to patients since the end of 2019 following more than 30 clinical trials and 1.2 million hours of use. We propose now, in collaboration with Tandem Diabetes Care and Dexcom, to introduce the next generation of algorithm technology insulin pump, and continuous glucose sensors. Making the system smaller, easy to use, and with a user interface perfectly suitable for children 2-6 years old and their parents/caregivers. At this point we can confirm that reliable technology has been developed and sufficient data have been accumulated to warrant a large-scale study aiming to establish this new state-of-the-art technology as a clinically accepted treatment for children (2-6 years old) with type 1 diabetes (T1D) and their families. We propose a large-scale multi-center clinical trial at 3 research sites around the United States that will enroll 102 2-6 years old children with T1D and at least 1 of their parents/caregivers, to use the system for 3 months in a 2:1 randomized, control parallel study comparing AP vs. Standard of Care (SoC). In addition, the study will conclude with a 3-month extension in which the SoC group will transition to use AP and the experimental group will continue with more relaxing follow up visits. All study sites are pediatric centers with extensive expertise in clinical trials in children and AP track record. We will show: (1) that glycemic control achieved by CLC will be superior to SoC therapy in terms of: (i) Reduced incidence of hypoglycemia without deterioration in HbA1c; (ii) Improved time within the target ranges of 70-180 mg/dl during the day and 70-140 mg/dl overnight; (iii) Improved HbA1c without increased risk of hypoglycemia, notably for those with HbA1c 7.5% at the baseline, and (iv) Reduced extreme glycemic events below 54 mg/dl and above 300 mg/dl, and fewer episodes of severe hypoglycemia, episodes of DKA, or other serious adverse events. (2) and that use of AP with real-time monitoring and cloud features will reduce diabetes distress and will result in: (i) Reduced fear of hypoglycemia, in both parent and child and better quality of life among parents/caregivers and children as compared to SoC; (ii) System acceptance and positive evaluation of the AP user interface and of the real-time remote monitoring/automated notification system; the latter will be particularly useful for parents when children are at pre-school/day care, and (iii) System reliability and usability meeting regulatory acceptance criteria. We therefore expect to test and validate an AP system that includes interacting Local (AP, near the child) and Global (Cloud/Real-time remote monitoring, available to parents) components, which in concert provide both optimal glucose control for 2-6 years old children with type 1 diabetes and peace of mind for their families.