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

 描述(申请人提供)：这一快速跟踪计划的目标是开发一种新的、稳定的非水高血糖素制剂，该制剂具有闭合循环输注泵系统和持续的血糖监测，用于治疗反复经历严重餐后低血糖的减肥手术后患者。这种方法将提供：(A)自动或半自动的胰高血糖素；(B)不会引发高血糖的个性化剂量；以及(C)提供更经济的治疗策略。在这类患者中，通过进食来纠正低血糖实际上会引发另一种后续的低血糖事件，而胰高血糖素的作用是在不引发过量胰岛素分泌的情况下提高血糖水平。因此，迫切需要改进治疗严重低血糖的方法，以维持健康，允许最佳营养，并提高减肥后低血糖(PBH)综合征患者的安全性。当前提案的主要目标与NIDDK肥胖症治疗和预防以及2型糖尿病治疗的研究优先事项直接相关。该项目的第一阶段工作将开发使用CGM信息的算法，以使用自动触发算法在存在低血糖的情况下触发实时警报，该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这种概念验证(POC)。该计划的第二阶段工作将把第一阶段的优化算法引入闭环泵系统，用于随机、盲目、安慰剂对照的临床试验。该项目中产生的数据还可能使未来的门诊研究成为可能，在这些研究中，患者可以在“真实”情况下测试该系统。我们认为，在OmniPod(R)中使用Xeris公司的高血糖素形成的闭环高血糖素(CLG)系统将是治疗PBH综合征的一种更有效的方法。

 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.