An Implanted Intraperitoneal (IP-IP) Artificial Pancreas; a quantum leap forward

描述(由申请人提供)：该项目的目标是开发一种用于1型糖尿病患者的腹膜内植入的闭环式血糖监测/胰岛素输送设备(又名人工胰腺)。人工胰腺可以改善患者的短期和长期健康和生活质量，并可以降低总体医疗成本。然而，目前大多数人工胰腺原型使用皮下胰岛素泵和皮下葡萄糖传感器，这与显著的滞后时间相关(分别为~60分钟和~10分钟)。此外，胰岛素输注部位和传感器每隔几天就需要更换一次，这增加了胰岛素吸收和血糖测量的可变性。这些滞后和变化对任何使用皮下胰岛素输送和葡萄糖传感的人工胰腺的性能施加了上限。幸运的是，这些挑战可以通过一种可植入的人工胰腺来克服，这种胰腺同时使用腹膜内胰岛素输送和腹膜内葡萄糖感应-IP-IP AP。与皮下胰岛素相比，腹膜内胰岛素在起效和抵消方面都更快、更可预测；与皮下传感相比，腹膜传感在跟踪血糖变化方面显得更准确和及时。在腹膜环境中，日内变异性最小，每年只需重新植入一次(泵每三个月经皮重新充填一次)。展望现实世界的影响，这项研究的最终目标是开发一种完全闭合的、可商业化的设备，与当前的泵/CGM疗法相比，总成本相同(或更低)。IP-IP AP的开发将是一个多学科的努力。因此，项目团队包括：一家开发基于荧光的植入式葡萄糖传感器的公司；一家开发可植入腹膜内的微型胰岛素泵的公司；一家开发热稳定、高浓度胰岛素类似物的公司；一家擅长腹膜内血糖传感的公司；一家擅长血糖控制算法的学术机构；以及一家擅长糖尿病技术的临床研究所。该项目有五个具体目标：1)使现有的基于荧光的葡萄糖传感器集成到腹膜内胰岛素导管中，并建立大约50个用于动物和人体研究的传感器导管；2)开发和制造新一代植入式、基于MEMS的胰岛素泵，可以作为闭环系统的一部分进行无线操作；3)确认热稳定的胰岛素类似物可在37℃的腹膜腔泵中使用长达一年，并表征类似物的腹膜内PK和PD；4)优化腹膜腔内感应和胰岛素注射的闭环控制算法，并用计算机模拟验证该算法；5)在猪实验中验证植入的人工胰腺，并在人体上进行先导研究。

DESCRIPTION (provided by applicant): The goal of this project is to develop an intraperitoneally implanted, closed-loop glucose-monitoring / insulin- delivery device (aka artificial pancreas) for people with type 1 diabetes. An artificial pancreas could improve patients short- and long-term health and quality of life, and it could decrease overall healthcare costs. However, most current artificial-pancreas prototypes use subcutaneous insulin pumps and subcutaneous glucose sensors, which are associated with significant lag times (~60 minutes and ~10 minutes, respectively). Furthermore, insulin infusion sites and sensors require replacement every several days, contributing to variability in insulin absorption and glucose measurement. These lags and variabilities impose a ceiling on the performance of any artificial pancreas that uses subcutaneous insulin delivery and glucose sensing. Fortunately, these challenges could be overcome by an implantable artificial pancreas that uses both intraperitoneal insulin delivery and intraperitoneal glucose sensing - an IP-IP AP. Compared to subcutaneous insulin, intraperitoneal insulin is faster and more predictable in both onset and offset; compared to subcutaneous sensing, intraperitoneal sensing appears more accurate and timely for tracking blood glucose changes. Intraday variability is minimal in the intraperitoneal environment, and re-implantation would be required only once per year (with the pump re-filled transcutaneously once every three months). Looking toward real-world impact, the ultimate goal of this research is development of a fully closed-loop, commercializable device with total costs that are identical (or lower) compared to current pump/CGM therapy. Development of an IP-IP AP will be a multidisciplinary effort. Thus, the project team includes: a company developing fluorescence-based implantable glucose sensors; a company developing intraperitoneally implantable, miniaturized insulin pumps; a company developing a heat-stable, highly concentrated insulin analog; a company with expertise in intraperitoneal glucose sensing; an academic institution with expertise in glucose-control algorithms; and a clinical research institut with expertise in diabetes technology. The project has five specific aims: 1) To adapt an existing fluorescence-based glucose sensor for integration into an intraperitoneal insulin catheter, and to build roughly 50 sensor-catheters for animal and human studies; 2) To develop and manufacture a next-generation implantable, MEMS-based insulin pump that can be wirelessly operated as part of a closed-loop system; 3) To confirm that the heat-stable insulin analog is compatible with use in an intraperitoneal pump at 37¿ C for up to one year, and to characterize the analog's intraperitoneal PK and PD; 4) To optimize a closed-loop control algorithm for intraperitoneal sensing and intraperitoneal insulin delivery, and to validate this algorithm with i silico simulations; 5) To validate the implanted artificial pancreas in swine studies, and to perform a pilot study in humans.