Automated Glucose Regulation to improve Diabetes Control and Outcomes for Pregnant Women with Type 1 Diabetes and Fetus

项目摘要 1型糖尿病（T1 D）患者妊娠与母体和胎儿高风险相关。严格血糖 控制是减少妊娠并发症的关键。然而，达到推荐的血糖目标是 这对大多数T1 D孕妇来说是一个挑战。当代闭环控制或人工胰腺 (AP)系统可以为这种未满足的临床需求提供最佳解决方案。然而，昼夜生理，激素 和葡萄糖在整个~40周妊娠期间的变化，胎儿和母亲血糖风险的变化， 关于该人群研究的严格规定限制了该队列的干预性研究， 约会因此，美国尚未在T1 D孕妇中研究AP技术。该财团 哈佛/马约诊所/Mt.西奈半岛和Sansum糖尿病研究所的目标是开发一个AP系统， 根据T1 D孕妇的个性化需求定制，并能够适应生理变化 孕期一系列短期监督临床研究将为该系统提供反馈 性能并将指示所需的改进。通过迭代过程，AP算法将被 修订和定稿。成功完成初始研究将导致4周单组妊娠 特定AP研究，可选择在妊娠期间延长AP。目前的研究将 在器官形成完成后招募受试者，并且在妊娠14-28周期间风险相对较低。 因此，该项目的总体目标是创建适应性妊娠知情AP技术，用于测试 随后的II期和III期随机临床试验，具体目标如下： 具体目标1：开发最先进的自动血糖控制系统，供长期使用 在T1 D妊娠的所有阶段。利用多中心分析获得的临床信息 糖尿病孕妇的血糖变异性、胰岛素管理和结局数据库，以设计一个 基于云的自适应决策支持系统（DSS）层。 具体目标2：评价第二次血糖监测期间自动血糖控制的安全性和可行性 在有监护的环境下进行三个月的T1 D检查将更新控制算法，以启用实时葡萄糖 胰岛素敏感性随时间变化的孕妇的管理。三项临床研究将在 进行了两项监督性48小时和一项为期1周的家庭研究，以评估 提出的控制策略，并最终确定算法的细节，将建立一个安全的AP系统， 孕妇 具体目标3：第2次和第3次期间自动血糖控制的扩展评价 妊娠三个月的T1 D。一项长期多中心单臂门诊AP研究（4周和可选 扩展阶段），以评估已开发的AP系统的安全性和有效性。

PROJECT ABSTRACT Pregnancy in patients with type 1 diabetes (T1D) is associated with high maternal and fetal risk. Tight glycemic control is critical to reduce pregnancy complications. However, achieving the recommended glycemic targets is very challenging for most pregnant women with T1D. Contemporary closed-loop control or artificial pancreas (AP) systems can offer optimal solutions to this unmet clinical need. However, diurnal physiological, hormonal and glucose changes throughout the ~40 week gestation, the changing glycemic risks to fetus and mother and the stringent regulations about research in this population have limited interventional studies in this cohort to date. As a result, AP technologies have not been studied in pregnant women with T1D in the US. The consortium of Harvard/Mayo Clinic/Mt. Sinai and Sansum Diabetes Research Institute aim to develop an AP system that is customized to the individual needs of pregnant women with T1D and is able to adapt to the physiologic changes during pregnancy. A series of short-term supervised clinical studies will provide feedback for the system performance and will indicate required improvements. Through an iterative process, the AP algorithm will be revised and finalized. The successful completion of the initial studies will lead to a 4-week single arm pregnancy specific AP study with the option of extension of AP for the duration of the pregnancy. The current studies will enroll subjects after organogenesis is complete and risk is relatively lower in the 14-28 week pregnancy period. The overall goal of this project is therefore to create adaptive pregnancy-informed AP technologies, for testing with subsequent phase 2 and phase 3 randomized clinical trials, in 3 Specific Aims as follows: Specific Aim 1: Develop a state of the art automated glucose control system for prolonged use during all stages of pregnancy in T1D. Leverage clinical information obtained by the analysis of a multicenter database of glycemic variability, insulin management and outcomes of pregnant women with T1D to design a cloud based adaptive decision support system (DSS) layer for the AP. Specific Aim 2: Evaluate the safety and feasibility of automated glucose control during the second trimester in a supervised setting for T1D. The control algorithm will be updated to enable real-time glucose management for pregnant women with time-varying insulin sensitivity profiles. Three clinical studies will be conducted, two supervised 48 hour and one 1-week home-based study to evaluate the safety and efficiency of the proposed control strategy and to finalize the algorithm details that will establish a safe AP system tailored for pregnant women. Specific Aim 3: Extended evaluation of automated glucose control during second and third trimesters of pregnancy in T1D. A prolonged multicenter single arm outpatient AP study (4 weeks and optional extension phase) will be conducted to evaluate the safety and effectiveness of the developed AP system.