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

描述（由申请人提供）：该项目的目标是为1型糖尿病患者开发一种腹腔内植入、闭环血糖监测/胰岛素输送装置（又名人工胰腺）。人工胰腺可以改善患者的短期和长期健康状况和生活质量，还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，这与明显的滞后时间（分别为~60分钟和~10分钟）有关。此外，胰岛素输注部位和传感器需要每隔几天更换一次，导致胰岛素吸收和葡萄糖测量的变化。这些滞后性和可变性限制了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。幸运的是，这些挑战可以通过植入式人工胰腺来克服，这种植入式人工胰腺同时使用腹腔胰岛素输送和腹腔葡萄糖传感（IP-IP AP）。与皮下胰岛素相比，腹腔胰岛素在起效和抵消方面更快，更可预测；与皮下传感相比，腹腔内传感对血糖变化的跟踪更为准确和及时。在腹腔内环境中，每天的变化是最小的，并且每年只需要重新植入一次（每三个月经皮重新填充一次泵）。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环、可商业化的设备，其总成本与目前的泵/CGM治疗相同（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；一家开发腹腔内植入式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；一家专门从事腹腔内葡萄糖检测的公司；专门研究血糖控制算法的学术机构；还有一个专门研究糖尿病技术的临床研究机构。该项目有五个具体目标：1)将现有的基于荧光的葡萄糖传感器集成到腹腔胰岛素导管中，并构建大约50个用于动物和人类研究的传感器导管；2)开发和制造下一代可植入的基于mems的胰岛素泵，该泵可以作为闭环系统的一部分进行无线操作；3)确认热稳定胰岛素模拟物可在37℃的腹腔泵中使用长达一年，并表征模拟物的腹腔内PK和PD；4)优化了一种用于腹腔传感和腹腔胰岛素输送的闭环控制算法，并用计算机仿真对该算法进行了验证；5)在猪的研究中验证植入人工胰腺，并在人体中进行初步研究。

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.