SBIR-STTR Award

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.

Public Health Relevance Statement:


Public Health Relevance:
The objective of this Fast-Track program is to further the development of 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 are at high risk for postprandial hypoglycemia.

Project Terms:
Aftercare; Algorithms; Amendment; bariatric surgery; Bariatrics; base; Blinded; Blood Glucose; Clinical; Clinical Research; Clinical Trials; cohort; Communication; Conduct Clinical Trials; Controlled Clinical Trials; Data; design; Detection; Development; Devices; dietary restriction; Dose; Drug Formulations; Drug Kinetics; Eating; effective therapy; Evaluation; Event; Exercise; experience; falls; Future; Glucagon; glucose monitor; Health; high risk; Human; Hyperglycemia; Hypoglycemia; improved; Infusion Pumps; Injection of therapeutic agent; Institutional Review Boards; insulin secretion; Life; Liquid substance; Longitudinal Studies; Masks; Measures; Medical; National Institute of Diabetes and Digestive and Kidney Diseases; Non-Insulin-Dependent Diabetes Mellitus; novel; nutrition; obesity prevention; obesity treatment; Octreotide; Outcome; Outpatients; patient population; Patients; Phase; Placebo Control; Population; Powder dose form; Preparation; prevent; programs; public health relevance; Pump; Randomized; Reactive hypoglycemia; Real-Time Systems; reconstitution; Research Priority; response; Safety; safety study; Saline; Seizures; sensor; Syndrome; System; Systems Integration; Temperature; Testing; Time; treatment strategy; Unconscious State; vehicular accident; verification and validation; Vial device

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.

Public Health Relevance Statement:


Public Health Relevance:
The objective of this Fast-Track program is to further the development of 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 are at high risk for postprandial hypoglycemia.

NIH Spending Category:
Bioengineering; Clinical Research; Clinical Trials and Supportive Activities; Diabetes; Nutrition; Obesity; Prevention

Project Terms:
Aftercare; Algorithms; Amendment; bariatric surgery; Bariatrics; base; Blinded; Blood Glucose; Clinical; Clinical Research; Clinical Trials; cohort; Communication; Conduct Clinical Trials; Controlled Clinical Trials; Data; design; Detection; Development; Devices; dietary restriction; Dose; Drug Kinetics; Eating; effective therapy; Evaluation; Event; Exercise; experience; falls; Formulation; Future; Glucagon; glucose monitor; Health; high risk; Human; Hyperglycemia; Hypoglycemia; improved; Infusion Pumps; Injection of therapeutic agent; Institutional Review Boards; insulin secretion; Life; Liquid substance; Longitudinal Studies; Masks; Measures; Medical; National Institute of Diabetes and Digestive and Kidney Diseases; Non-Insulin-Dependent Diabetes Mellitus; novel; nutrition; obesity prevention; obesity treatment; Octreotide; Outcome; Outpatients; patient population; Patients; Phase; Placebo Control; Population; Powder dose form; Preparation; prevent; programs; Pump; Randomized; Reactive hypoglycemia; Real-Time Systems; reconstitution; Research Priority; response; Safety; safety study; Saline; Seizures; sensor; Syndrome; System; Systems Integration; Temperature; Testing; Time; treatment strategy; Unconscious State; vehicular accident; verification and validation; Vial device