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(T1D)患者怀孕与母婴风险高相关。高血糖 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 对于大多数患有T1D的孕妇来说，这是非常具有挑战性的。当代闭环控制或人工胰腺 (AP)系统可以为这一未得到满足的临床需求提供最佳解决方案。然而，昼夜生理，荷尔蒙 和血糖在整个40周妊娠期间的变化，胎儿和母亲血糖风险的变化以及 关于这一人群研究的严格规定将该队列中的干预性研究限制为 约会。因此，在美国，AP技术还没有在患有T1D的孕妇身上进行研究。该财团 哈佛大学/梅奥诊所/Mt.西奈和三苏姆糖尿病研究所的目标是开发一种AP系统， 为患有T1D的孕妇量身定做，能够适应生理变化 在怀孕期间。一系列短期监督的临床研究将为该系统提供反馈。 性能，并将指出需要改进的地方。通过迭代过程，AP算法将被 修订和定稿。初步研究的成功完成将导致4周的单臂妊娠 特定的AP研究，可选择在妊娠期间延长AP。目前的研究将 在器官发生完成后登记受试者，在怀孕14-28周期间风险相对较低。 因此，该项目的总体目标是创建自适应的怀孕知情AP技术，用于测试 随后的2期和3期随机临床试验，具体目标如下： 具体目标1：开发一种可长期使用的最先进的自动血糖控制系统 在妊娠的各个阶段，在T1d。利用通过多中心分析获得的临床信息 T1D孕妇血糖变异性、胰岛素管理和结局的数据库设计 AP的基于云的自适应决策支持系统(DSS)层。 具体目标2：评估第二阶段自动血糖控制的安全性和可行性 在T1D的监督环境中怀孕三个月。控制算法将被更新以实现实时血糖 具有时变胰岛素敏感性特征的孕妇的管理。三项临床研究将是 进行了两项为期48小时的监督家庭研究和一项为期一周的家庭研究，以评估 提出的控制策略和最终确定的算法细节，将建立一个专为 怀孕的女人。 具体目标3：在第二次和第三次期间扩大对自动血糖控制的评估 妊娠三个月在T1d。一项长期的多中心单臂门诊AP研究(4周和可选 将进行扩展阶段)，以评估已开发的接入点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.