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

用于治疗减肥后低血糖的闭环胰高血糖素泵

• 批准号: 9100962
• 负责人: Eyal Dassau
• 金额: $ 81.61万
• 依托单位: XERIS PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9100962
• 关键词: Aftercare; Algorithms; Amendment; Bariatrics; Blinded; Blood Glucose; Clinical; Clinical Research; Clinical Trials; Communication; Conduct Clinical Trials; Controlled Clinical Trials; Data; Detection; Development; Devices; Dose; Drug Kinetics; Eating; Evaluation; Event; Exercise; Formulation; Future; Glucagon; Health; Human; Hyperglycemia; Hypoglycemia; Infusion Pumps; Injection of therapeutic agent; Institutional Review Boards; Life; Liquid substance; Longitudinal Studies; Masks; Measures; Medical; National Institute of Diabetes and Digestive and Kidney Diseases; Non-Insulin-Dependent Diabetes Mellitus; Octreotide; Outcome; Outpatients; Patients; Phase; Placebo Control; Population; Powder dose form; Preparation; Pump; Randomized; Reactive hypoglycemia; Real-Time Systems; Research Priority; Safety; Saline; Seizures; Syndrome; System; Systems Integration; Temperature; Testing; Time; Unconscious State; Vial device; bariatric surgery; base; cohort; design; dietary restriction; effective therapy; experience; falls; glucose monitor; high risk; improved; insulin secretion; novel; nutrition; obesity prevention; obesity treatment; patient population; prevent; programs; reconstitution; response; safety study; sensor; treatment strategy; vehicular accident; verification and validation

 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.

 描述（由申请人提供）：该快速通道计划的目标是开发一种新型、稳定的非水胰高血糖素制剂，配备闭环输注泵系统并进行连续血糖监测，用于治疗反复出现严重餐后低血糖的减肥手术后患者。该方法将提供：（a）自动化或半自动化胰高血糖素； (b) 不会引发高血糖的个性化剂量； (c) 提供更经济的治疗策略。在这个患者群体中，通过饮食来纠正低血糖实际上可能会引发另一次后续的低血糖事件，而胰高血糖素则可以增加血糖水平，而不会引发过量的胰岛素分泌。因此，迫切需要改进严重低血糖的治疗方法，以维持肥胖后低血糖（PBH）综合征患者的健康、提供最佳营养并提高安全性。当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。该项目的第一阶段工作将开发使用 CGM 信息的算法，在出现低血糖时使用自动触发算法触发实时警报，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一概念验证 (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、盲法、安慰剂对照临床试验。该项目中生成的数据还可以支持未来的门诊研究，患者可以在“现实生活”情况下测试该系统。我们建议，在 OmniPod(r) 中使用 Xeris 胰高血糖素形成的闭环胰高血糖素 (CLG) 系统将是治疗 PBH 综合征的更有效方法。