NCT03424044

Three Way Crossover Closed Loop Study With Xeris Glucagon

A Randomized, Three-way, Cross-over Study to Assess the Efficacy of a Dual-hormone Closed-loop System With XeriSol™ Glucagon vs Closed-loop System With Insulin Only vs a Predictive Low Glucose Suspend System

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 23 (actual)
• Sponsor: Oregon Health and Science University · Academic / Other
• Sex: All
• Age: 21 Years – 50 Years
• Healthy volunteers: Not accepted

Summary

Closed-loop systems are an emerging technology that automate hormone delivery. They are quickly paving the way to revolutionize the treatment of type 1 diabetes. Several categories have emerged: dual-hormone (insulin and glucagon) closed-loop systems and closed-loop systems with insulin only, one variety of which is the low glucose suspend safety feature now available from Medtronic (MiniMed640G with SmartGuard). The study described within this protocol is designed to test the efficacy of a new closed-loop algorithm for managing blood glucose in people with type 1 diabetes before and after exercise. The new algorithm will have 3 modes: a single hormone insulin only mode, a dual-hormone insulin and glucagon mode and an insulin only mode with predictive low glucose suspend, all with an exercise detection algorithm. The purpose of this study is to determine whether a dual hormone AP using a stable investigational glucagon with an exercise detection algorithm outperforms both single hormone AP and a low glucose suspend algorithm.

Detailed description

Subjects will undergo three approximately 76 hour studies. During each of these intervention visits, subjects will wear an Omnipod to deliver insulin and a Dexcom G5 CGM to measure glucose. In the dual-hormone closed-loop study, participants will wear a second Omnipod filled with XeriSol™ glucagon. The first day of intervention visit will be a 12 hour inpatient visit with the subsequent time spent as an outpatient. The subject will come back to the research center on Day 4 in the morning to remove all devices. The blood glucose control system is called the Artificial Pancreas Controller (APC). During one of the studies, glucose will be controlled using the dual hormone mode. During another study, glucose will be controlled using the single hormone mode. The single and dual hormone modes of the APC controller determine insulin only and insulin with glucagon delivery rates based on proportional and derivative error and contain an exercise detection component. During the other study, glucose will be controlled using a predictive low glucose suspend (PLGS) mode. In the PLGS mode, the APC will be programmed with the subject's basal profile(s) which will be transmitted to the Omnipod Personal Diabetes Manager (PDM) and allow for boluses to be inputted by the subjects for meals and corrections using their typical carb ratios and correction factors. However, this system will have a safety feature to suspend insulin delivery when sensor glucose is predicted to go below a threshold. Treatment order will be randomized. Subjects will arrive at the clinic at approximately 7 or 8am for the inpatient visits. Subjects will eat breakfast and lunch at approximately 8:30am, noon and 6pm respectively. The dinner meal will be consumed while the subject is at home. Subjects will exercise on a treadmill for 45 minutes. Subjects will be discharged 9 hours after admission. The subject will then go home for the remainder of the study visit. Studies will be remotely monitored. Subjects will return to OHSU on Day 4 for removal of all devices. During each study, the subject will wear one subcutaneous DexcomTM G5 continuous glucose monitoring (CGM) system. The CGM system will provide sensed glucose data every 5 minutes. The accuracy of the sensed data will be obtained by reference measurements of capillary blood glucose. Sensed glucose data will be wirelessly transmitted via Bluetooth Low Energy (BTLE) from the Dexcom G5 transmitter to the Nexus 5 master controller every five minutes. The controller for all 3 modes is a Google Nexus 5 phone. The smart phone will wirelessly communicate via BTLE to an Omnipod through a PDM (Insulet Corp. ) for automated insulin delivery or in the case of dual-hormone AP, one used for automated insulin delivery and one for automated glucagon delivery. A physician or nurse practitioner will be present for study start-up, will be on campus for exercise on Day 1 and will be immediately available on call at all other times.

Conditions

• Type1diabetes

Interventions

Type	Name	Description
DEVICE	Artificial Pancreas Controller in Dual Hormone Mode	The artificial pancreas controller contains an algorithm for managing blood glucose in people with type 1 diabetes which includes an exercise detection component. The algorithm has 3 modes: a single hormone closed-loop insulin only mode, a dual-hormone closed-loop insulin and glucagon mode and an insulin only mode with predictive low glucose suspend. The Closed-loop Artificial Pancreas Controller includes insulin and glucagon delivery algorithm implemented on a smart phone, utilizing sensor glucose values from a Dexcom G5 sensor and sending delivery commands to two Omnipod insulin pumps, one filled with insulin and one with glucagon.
DEVICE	Artificial Pancreas Controller in Single Hormone Mode	The artificial pancreas controller contains an algorithm for managing blood glucose in people with type 1 diabetes which includes an exercise detection component. The new algorithm will have 3 modes: a single hormone closed-loop insulin only mode, a dual-hormone closed-loop insulin and glucagon mode and an insulin only mode with predictive low glucose suspend. The Closed-loop Artificial Pancreas Controller includes insulin delivery algorithm implemented on a smart phone, utilizing sensor glucose values from a Dexcom G5 sensor and sending delivery commands to one Omnipod pump filled with insulin.
DEVICE	Artificial Pancreas Controller in Predictive Low Glucose Suspend Mode	The artificial pancreas controller contains an algorithm for managing blood glucose in people with type 1 diabetes which includes an exercise detection component. The new algorithm will have 3 modes: a single hormone closed-loop insulin only mode, a dual-hormone closed-loop insulin and glucagon mode and an insulin only mode with predictive low glucose suspend. The Closed-loop Artificial Pancreas Controller includes insulin delivery algorithm implemented on a smart phone, utilizing sensor glucose values from a Dexcom G5 sensor and sending delivery commands to one Omnipod insulin pump filled with insulin.
DRUG	XeriSol glucagon	XeriSol glucagon is an investigational drug that is a stable, soluble liquid glucagon formulation that can be injected or administered through an insulin pump. XeriSol glucagon will be used to fill the Omnipod to deliver glucagon for the Artificial Pancreas Controller in Dual Hormone mode.

Timeline

• Start date: 2018-03-29
• Primary completion: 2019-05-17
• Completion: 2019-05-17
• First posted: 2018-02-06
• Last updated: 2020-05-27
• Results posted: 2020-05-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study
• FDA-regulated device study