Three Way Crossover Closed Loop Study With Xeris Glucagon
Condition: Type1diabetes
MeSH terms: Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): Artificial Pancreas Controller in Dual Hormone Mode; Artificial Pancreas Controller in Single Hormone Mode; Artificial Pancreas Controller in Predictive Low Glucose Suspend Mode; XeriSol glucagon
Intervention type(s): Device; Device; Device; Drug
Intervention description(s): 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.; 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.; 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.; 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.
Intervention MeSH terms: Glucagon; Pancrelipase; Pancreatin; Hormones
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: glucagon; closed-loop; Omnipod; exercise