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

描述(由申请人提供)：体外闭环血糖控制系统的最终实施例将是由三个组件组成的便携式设备：连续血糖监测仪(CGM)、连续皮下(SC)药物输注设备(例如胰岛素泵)和控制算法。控制算法通过从CGM接收葡萄糖数据流，根据该数据流做出治疗决定，并向药物输注设备发出命令，将其他两个组件连接起来。我们设计并测试了基于静脉血糖数据流(在糖尿病猪和1型糖尿病患者中)或CGM数据流(在糖尿病猪中)安全有效地调节血糖(BG)水平的闭环控制系统。我们在糖尿病猪身上进一步测试了我们的基于CGM的闭环控制系统，使用了仅使用胰岛素的配置和双激素(胰岛素和高血糖素)配置。根据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1型糖尿病患者提供安全有效的血糖控制。我们的目标是通过在马萨诸塞州总医院的Mallinckrodt临床研究中心对患有1型糖尿病的健康成年志愿者(18岁及以上)进行人体试验来验证这一假设并优化我们的闭环系统。为了实现这一目标，我们提出了以下三个具体目标：(1)基于CGM的间质-液体(ISF)血糖数据，测试我们的控制系统(在双激素和仅使用胰岛素的配置下)在调节成人1型糖尿病患者血糖方面的安全性和有效性；(2)使用相同的控制系统重复Aim 1的研究，并在研究方案中增加有组织的运动时段；(3)使用完全集成的基于PDA的便携式控制系统在成人1型糖尿病患者中进行为期5天的连续闭环研究。 公共卫生相关性：良好、一致地管理1型糖尿病患者的血糖水平对于预防或减少健康并发症至关重要。我们的目标是开发一种工程系统，通过开发一种计算机程序，将自动且频繁地估计人的血糖的传感设备与自动输送胰岛素以降低血糖的小泵连接起来，从而开发出一种自动管理1型糖尿病患者血糖的工程系统。如果成功，该系统将提供良好和安全的血糖管理，并减少糖尿病可能产生的健康并发症。

DESCRIPTION (provided by applicant): 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 components 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 volunteers (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. PUBLIC HEALTH RELEVANCE: Good, consistent management of blood sugar levels in people with type 1 diabetes is essential to prevent or minimize health complications. Our goal is to develop an engineering system that would automatically manage blood sugar in people with type 1 diabetes by developing a computer program that would link a sensing device that automatically and frequently estimates a person's blood sugar with a small pump that automatically delivers insulin to lower blood sugar. If successful, the system will provide good and safe management of blood sugar, and reduce the health complications that may arise with diabetes.