A multicenter outpatient trial of a bihormonal bionic pancreas

描述(由申请人提供)：第一个体外闭环血糖(BG)控制系统或仿生内分泌胰腺(BP)的最终实施例是一种可穿戴设备，包括：连续血糖监测仪(CGM)、药物输注泵和控制算法，该控制算法基于CGM的血糖数据自动发布泵上的剂量。我们在波士顿大学(BU)的临床前猪研究以及儿科和成人1型患者的住院可行性研究中设计并广泛测试了我们的荷尔蒙BP 马萨诸塞州综合医院(MGH)的糖尿病。我们最近制造了第一台真正可穿戴的移动荷尔蒙BP，最近获得了FDA的批准，可以在我们的第一项门诊过渡研究中测试它。该系统围绕iPhone 4S(Apple)构建，它运行我们的控制算法，并协调G4白金CGM(DexCom)和两个(胰岛素/胰高血糖素)t：超薄胰岛素泵(串联式糖尿病护理)之间的通信。我们已经开始了我们的门诊研究(2013年2月)，该研究涉及对成年1型糖尿病患者进行为期5天的持续闭环控制实验。受试者睡在密歇根州立大学附近的一家酒店，并在波士顿毕肯山社区周围三平方英里的范围内度过一天。他们白天由护士陪同，晚上在隔壁的酒店房间里有护士随叫随到。受试者只需提供他们的体重来开始血压，然后血压自动控制BG五天。受试者不需要在任何时候触发或手动提供任何胰岛素推注，但BP允许他们触发由BP自动确定和调整的可选膳食推注剂量。我们所指的Beacon Hill研究将于2013年6月结束，7月和8月我们的夏令营研究将涉及马萨诸塞州中部两个糖尿病营地的6-21岁1型糖尿病儿童。我们最近已经向FDA提交了夏令营研究的IDE申请，并向MGH IRB提交了临床方案，以供审查，并正在等待两者在4月底之前做出决定。该项目旨在使用我们的可穿戴BP在成人1型糖尿病患者的多中心门诊环境中进行倒数第二次过渡研究。在随机交叉设计中，这项研究将从四个医疗中心招募48名患有1型糖尿病的医疗中心工作人员。在工作中，受试者将继续他们的正常工作。在随机的方式中，一半的受试者将遵循他们通常的糖尿病护理方案12天，而另一半的受试者将 由我们的BP进行12天的闭环控制。在两天的冲洗期后，两组的受试者都将交叉到另一组研究臂。因此，每个主体都将充当自己的控制者。工作分心可以让我们对常规护理疗法进行现实的评估，并给我们的BP带来现实世界的挑战。选择在医疗中心工作的受试者可以让我们的研究人员进行密切的集中监控。我们的多中心医院员工研究将是我们使用当前BP的最后一次过渡性研究，并将在2015-2016年 Pivotal试验，测试我们的BP的最终体现(在未来24个月内建造和验证)，我们打算在2016年底向FDA提交上市前批准申请中提出。

DESCRIPTION (provided by applicant): The ultimate embodiment of the first extracorporeal closed-loop blood-glucose (BG) control system, or bionic endocrine pancreas (BP), is a wearable device consisting of: a continuous glucose monitor (CGM), a drug infusion pump, and a control algorithm, which autonomously issues doses on the pump based on glucose data from the CGM. We have designed and extensively tested our hormonal BP in preclinical pig studies at Boston University (BU) and in inpatient feasibility studies in pediatrics and adults with type 1 diabetes at the Massachusetts General Hospital (MGH). We have recently built the first truly wearable mobile hormonal BP and have recently received FDA approval to test it in our first outpatient transitional study. The system is built around an iPhone 4S (Apple), which runs our control algorithm and coordinates communication between a G4 Platinum CGM (DexCom) and two (insulin/glucagon) t:slim insulin pumps (Tandem Diabetes Care). We have begun our outpatient study (February, 2013), which involves 5-day experiments of continuous closed-loop control in adults with type 1 diabetes. Subjects sleep in a hotel near MGH and spend the day within a three square mile area around Boston's Beacon Hill neighborhood. They are accompanied by a nurse during the day, and by night a nurse is on call in an adjacent hotel room. Subjects provide only their weight to start the BP, which then automatically controls BG for five days. Subjects need not trigger or manually deliver any insulin bolus at any time but the BP allows them to trigger optional meal priming bolus doses that are automatically determined and adapted by the BP. Our Beacon Hill Study, as we refer to it, will conclude in June, 2013, and be followed in July and August by our Summer Camp Study, which will involve children 6-21 years old with type 1 diabetes at two diabetes camps in central Massachusetts. We have recently submitted for review our IDE application for the Summer Camp Study to the FDA and the clinical protocol to the MGH IRB and are awaiting decisions from both by the end of April. This project aims to conduct our penultimate transitional study using our wearable BP in a multi-center out- patient setting in adults with type 1 diabetes. In a randomized cross-over design, the study will enroll 48 medical center staff members with type 1 diabetes from four medical center sites. While at work, subjects will go about their normal routines. In a randomized fashion, half of the subjects will follow their usual diabetes care regimen for 12 days while the other half will be under closed-loop control by our BP for 12 days. After a two-day washout period, subjects in both groups will crossover to the other study arm. Thus, each subject will serve as their own control. Work distractions allow a realistic assessment of usual-care therapy and provide real-world challenges to our BP. Choosing subjects who work in medical centers allows for close centralized monitoring by our study staff. Our multi-center Hospital Staff Study, as we refer to it will be our last transitional study to use our current BP, and will be followed in 2015-2016 by our pivotal trial, testing our BP in its ultimate embodiment (built and validated over the next 24 months) that we intend to put forward in a pre-market approval application to the FDA in late 2016.