Closed-Loop Glucagon Pump for Treatment of Post-Bariatric Hypoglycemia

 描述（由申请方提供）：本快速通道项目的目的是开发一种新型、稳定的非水性胰高血糖素制剂，该制剂配有闭环输注泵系统和持续血糖监测，用于治疗发生反复重度餐后低血糖的减肥手术后患者。这一办法将提供：（a）自动或半自动胰高血糖素;（B）不会引发高血糖症的个性化给药;和（c）提供更经济的治疗策略。在该患者人群中，进食纠正低血糖实际上可触发另一个后续低血糖事件，而胰高血糖素可增加血糖水平而不触发过量胰岛素分泌。因此，迫切需要改善治疗严重低血糖的方法，以维持健康，允许最佳营养，并提高肥胖后低血糖（PBH）综合征患者的安全性。目前提案的主要目标与NIDDK肥胖治疗和预防以及2型糖尿病治疗的研究重点直接相关。本项目的I期工作将使用CGM信息开发算法，以使用自动触发算法在存在低血糖时触发实时警报，该自动触发算法将从泵中部署和输送一定剂量的可溶性胰高血糖素，并在临床环境中测试该概念验证（POC）。该项目的第二阶段工作将把第一阶段的优化算法应用到闭环泵系统中，用于随机、设盲、安慰剂对照的临床试验。该项目中生成的数据也可能使未来的门诊研究成为可能，患者可以在“现实生活”中测试该系统。我们建议，在OmniPod（r）中使用Xeris胰高血糖素的闭环胰高血糖素（CLG）系统将是PBH综合征的更有效治疗方法。

 DESCRIPTION (provided by applicant): The objective of this Fast-Track program is to develop a novel, stable non-aqueous glucagon formulation with an infusion pump system in closed-loop with continuous glucose monitoring, for treatment of post-bariatric surgery patients who have experienced repetitive severe postprandial hypoglycemia. This approach will provide: (a) automated or semi-automated glucagon; (b) personalized dosing that will not trigger hyperglycemia; and (c) provide a more economical treatment strategy. In this patient population, eating to correct hypoglycemia can actually trigger another subsequent hypoglycemic event, whereas glucagon acts to increase blood glucose levels without triggering excess insulin secretion. Thus there is an urgent need for improved approaches for the treatment of severe hypoglycemia to maintain health, allow optimal nutrition, and improve safety in patients with post-bariatric hypoglycemia (PBH) syndrome. The primary objective of the current proposal is directly relevant to the NIDDK research priorities for obesity treatment and prevention, as well as type 2 diabetes treatment. The Phase I effort of this project will develop algorithms using CGM information to trigger real-time alerts in the presence of hypoglycemia using an automated trigger algorithm that will deploy and deliver a dose of soluble glucagon from a pump, and test this proof-of-concept (POC) in a clinical setting. The Phase II effort of this program will take th optimized algorithm from Phase I into a closed-loop pump system for use in a randomized, blinded, placebo-controlled clinical trial. The data generated in the project may also enable future outpatient studies in which patients can test the system in "real-life" situations. We propose that the resulting closed-loop glucagon (CLG) system with Xeris' glucagon in an OmniPod(r) will be a more effective treatment for PBH syndrome.