Clinical trials of a closed-loop control system for type 1 diabetes management

体外闭环血糖控制系统的最终实施方案将是便携式的， 包括三个组件：连续葡萄糖监测仪（CGM），连续皮下（SC）药物 输注设备（例如胰岛素泵）和控制算法。控制算法将其他两个COM- 通过从CGM接收葡萄糖数据流，基于该数据做出治疗决策， 流，并向药物输注装置发出命令。我们已经设计并测试了闭环控制 基于静脉血糖（BG）数据流安全有效地调节BG水平的系统 (in糖尿病猪和1型糖尿病患者）或CGM数据流（糖尿病猪）。我们进一步 在糖尿病猪中测试了我们基于CGM的闭环控制系统， 双激素（胰岛素和胰高血糖素）构型。基于我们积极的临床前结果，我们假设， 我们的基于CGM的闭环血糖控制系统可以为型糖尿病患者提供安全有效的血糖控制。 1例糖尿病。我们的目标是测试这一假设，并优化我们的闭环系统进行人类 在马萨诸塞州综合医院的Mallinckrodt临床研究中心对健康成人进行的试验， 1型糖尿病患者的饮食习惯我们建议从以下三个方面达到这个目标 具体目标：（1）测试我们的对照系统（双激素和仅胰岛素）的安全性和有效性 基于来自以下研究的脑脊液（ISF）葡萄糖数据， a CGM，（2）使用相同的控制系统重复目标1的研究，并增加结构化的周期 研究方案中的运动，以及（3）使用完全 基于PDA的便携式控制系统在成人1型糖尿病患者中的应用

The ultimate embodiment of an extracorporeal closed-loop blood-glucose control system will be a portable de- vice consisting of three components: a continuous glucose monitor (CGM), a continuous subcutaneous (SC) drug infusion device (e.g. an insulin pump), and a control algorithm. The control algorithm links the other two com- ponents by receiving the glucose data stream from the CGM, making a therapeutic decision based on that data stream, and issuing commands to the drug infusion device. We have designed and tested closed-loop control systems that safely and effectively regulate blood-glucose (BG) levels based on either a venous BG data stream (in diabetic pigs and in people with type 1 diabetes) or a CGM data stream (in diabetic pigs). We have further tested our CGM-based closed-loop control system in diabetic pigs using both an insulin-only configuration and a bihormonal (insulin and glucagon) configuration. Based on our positive preclinical results, we hypothesize that our CGM-based closed-loop glucose-control system can provide safe and effective BG control in people with type 1 diabetes. Our objective is to test this hypothesis and optimize our closed-loop system by conducting human trials in the Mallinckrodt Clinical Research Center at the Massachusetts General Hospital on healthy adult vol- unteers (18 years and older) with type 1 diabetes. We propose to achieve this objective with the following three specific aims: (1) to test the safety and efficacy of our control system (in both the bihormonal and insulin-only configurations) in regulating BG in adults with type 1 diabetes based on interstitial-fluid (ISF) glucose data from a CGM, (2) to repeat the study of Aim 1 using the same control system with the addition of periods of structured exercise in the study protocol, and (3) to conduct 5-day continuous closed-loop in-patient studies using a fully integrated PDA-based portable control system in adults with type 1 diabetes.