A multicenter outpatient trial of a bihormonal bionic pancreas

描述（由申请人提供）：第一体外闭环血糖（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：连续葡萄糖监测仪（CGM）、药物输注泵和控制算法，该控制算法基于来自CGM的葡萄糖数据自主地在泵上发出剂量。我们已经在波士顿大学（BU）的临床前猪研究以及1型糖尿病患者的儿科和成人住院可行性研究中设计并广泛测试了我们的激素BP 糖尿病在马萨诸塞州总医院（MGH）。我们最近制造了第一个真正可穿戴的移动的激素BP，最近获得了FDA的批准，在我们的第一个门诊过渡研究中进行测试。该系统围绕iPhone 4S（Apple）构建，它运行我们的控制算法并协调G4 Platinum CGM（DexCom）和两个（胰岛素/胰高血糖素）t：超薄胰岛素泵（Tandem Diabetes Care）之间的通信。我们已经开始了我们的门诊研究（2013年2月），其中包括在1型糖尿病成人中进行为期5天的连续闭环控制实验。受试者睡在MGH附近的一家酒店，并在波士顿灯塔山附近三平方英里的区域内度过一天。他们白天由一名护士陪同，晚上则由一名护士在邻近的旅馆房间待命。受试者仅提供他们的体重来启动BP，然后BP自动控制BG五天。受试者不需要在任何时间触发或手动输送任何胰岛素大剂量，但BP允许他们触发由BP自动确定和调整的可选餐前预充大剂量。我们提到的比肯山研究将于2013年6月结束，随后在7月和8月进行夏令营研究，该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，正在等待4月底的决定。该项目旨在在多中心门诊环境中使用我们的可穿戴BP对1型糖尿病成人进行倒数第二项过渡性研究。在一项随机交叉设计中，该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。在工作的时候，实验对象将进行他们的日常工作。以随机方式，一半受试者将遵循其常规糖尿病护理方案12天，而另一半将 由BP闭环控制12天两天洗脱期后，两组受试者将交叉至另一研究组，因此，每例受试者将作为自己的对照。工作分心可以对日常护理治疗进行现实评估，并为我们的BP提供现实挑战。选择在医疗中心工作的受试者，允许我们的研究工作人员进行密切的集中监测。我们的多中心医院员工研究，正如我们所提到的，将是我们使用当前BP的最后一项过渡性研究，并将在2015-2016年由我们的 关键性试验，测试我们的BP的最终实施方案（在未来24个月内构建和验证），我们打算在2016年底向FDA提交上市前批准申请。

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.