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

UVA 先进自动胰岛素输送系统在幼儿临床护理中的应用：血糖控制、监管接受和日常使用优化

• 批准号: 10265602
• 负责人: MARC D BRETON
• 金额: $ 143.74万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-17 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10265602
• 关键词: 6 year old; Acute; Adolescent; Adult; Affect; Age; Algorithms; American; Artificial Pancreas; Autoimmune Diseases; Caregivers; Caring; Cellular Phone; Charge; Child; Child Welfare; Childhood; Chronic; Clinical; Clinical Trials; Collaborations; Complex; Complications of Diabetes Mellitus; Consensus; Consumption; Data; Day Care; Deterioration; Development; Diabetes Mellitus; Ecosystem; Enrollment; Equilibrium; European; Evaluation; Event; Excess Mortality; Exposure to; FDA approved; Family; Family dynamics; Focus Groups; Fright; General Population; Generations; Glucose; Glycosylated hemoglobin A; Goals; Guidelines; Hour; Hyperglycemia; Hypoglycemia; Incidence; Insulin; Insulin Infusion Systems; Insulin deficiency; Insulin-Dependent Diabetes Mellitus; Intervention; Life; Measurement; Medical; Metabolic Control; Methods; Mind; Modality; Modernization; Multi-Institutional Clinical Trial; Neurocognitive; Notification; Nursery Schools; Outcome; Parents; Participant; Pathway interactions; Patients; Pattern; Psychometrics; Psychosocial Factor; Pump; Quality of life; Randomized; Randomized Clinical Trials; Regimen; Research; Risk; Safety; Serious Adverse Event; Signal Transduction; Site; Sports; System; Technology; Testing; Time; Translations; United States; United States National Institutes of Health; Universities; Variant; Virginia; Visit; Vulnerable Populations; analog; base; blood glucose regulation; clinical care; clinically significant; design; diabetes distress; diabetes management; diabetes risk; digital treatment; early childhood; expectation; experimental group; follow-up; glucose monitor; glucose sensor; glycemic control; improved; international center; meetings; next generation; novel; peace; pediatric patients; peer; preference; prevent; prototype; psychologic; psychosocial; real time monitoring; remote monitoring; simulation; standard of care; success; usability

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.

2011年我们提出人工胰腺（AP）系统是一个数字化治疗生态系统的想法 根据患者/家属的喜好和信号可用性提供不同的治疗方式。经过广泛 经过世界各地的测试，我们的CLC算法和AP组件已在商业系统中实现 （Dexcom，以前称为 TypeZero、InControl 和 Tandem t:slim X2 with ControlIQ）自年底起可供患者使用 2019 年，经过 30 多项临床试验和 120 万小时的使用。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，以及 连续葡萄糖传感器。使系统更小，易于使用，并且具有完美合适的用户界面 适合 2-6 岁的儿童及其父母/照顾者。至此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来保证进行大规模研究，旨在建立 这种最先进的新技术已成为临床上接受的 1 型儿童（2-6 岁）治疗方法 糖尿病（T1D）及其家人。我们提议在 3 个研究中心进行大规模多中心临床试验 美国将招募 102 名 2-6 岁 T1D 儿童和至少 1 位父母/照顾者， 在比较 AP 与标准护理的 2:1 随机对照平行研究中使用该系统 3 个月 （SoC）。此外，该研究将以 3 个月的延期结束，其中 SoC 小组将过渡到使用 美联社和实验组将继续进行更加轻松的随访。所有研究地点都是儿科的 中心在儿童临床试验和 AP 跟踪记录方面拥有丰富的专业知识。我们将展示： (1) CLC 实现的血糖控制在以下方面优于 SoC 疗法： (i) 降低糖尿病发生率 HbA1c 没有恶化的低血糖； (ii) 改善在 70-180 mg/dl 目标范围内的时间 白天和过夜 70-140 mg/dl； (iii) 在不增加低血糖风险的情况下改善 HbA1c，特别是对于 基线时 HbA1c 为 7.5% 的患者，以及 (iv) 极端血糖事件减少至低于 54 mg/dl 及以上 300 mg/dl，严重低血糖、DKA 或其他严重不良事件的发生次数较少。 (2) 使用具有实时监测和云功能的 AP 将减少糖尿病的困扰，并将导致 (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 和儿童与 SoC 相比； (ii) AP 用户界面的系统接受度和积极评价 实时远程监控/自动通知系统；后者对父母特别有用 当儿童在学前班/日托中心时，以及 (iii) 系统可靠性和可用性满足监管机构的认可 标准。 因此，我们希望测试和验证一个 AP 系统，其中包括交互的本地（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1型糖尿病儿童提供最佳血糖控制，让家人安心。