Three Way Crossover Closed Loop Study With Xeris Glucagon
Condition: Type1diabetes
MeSH terms: Diabetes Mellitus, Type 1
Intervention: 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 description: 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
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 21 Years
Maximum age: 50 Years
Healthy volunteers: No
Keywords: glucagon; closed-loop; Omnipod; exercise

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of type 1 diabetes mellitus for at least 1 year.

          -  Male or female subjects 21-50 years of age.

          -  Physically willing and able to perform 45 min of exercise.

          -  Current use of an insulin pump.

          -  Lives with another person age 18 or older who will be present while subject exercises
             at home and that can attend the training on using the system.

          -  Lives within 40 miles of OHSU main campus.

          -  HbA1c <= 10% at screening.

          -  Total daily insulin requirement is less than 139 units/day.

          -  Current use of a phone or other device so can be contacted by study staff off-campus.

          -  Willingness to follow all study procedures, including attending all clinic visits.

          -  Willingness to sign informed consent and HIPAA documents.

        Exclusion Criteria:

          -  Female of childbearing potential who is pregnant or intending to become pregnant or
             breast-feeding, or is not using adequate contraceptive methods. Acceptable
             contraception includes birth control pill/patch/vaginal ring, Depo-Provera, Norplant,
             an IUD, the double barrier method (the woman uses a diaphragm and spermicide and the
             man uses a condom), or abstinence.

          -  Any cardiovascular disease, defined as a clinically significant EKG abnormality at the
             time of screening or any history of: stroke, heart failure, myocardial infarction,
             angina pectoris, or coronary arterial bypass graft or angioplasty. Diagnosis of 2nd
             and 3rd degree heart block or any non-physiological arrhythmia judged by the
             investigator to be exclusionary.

          -  Renal insufficiency (GFR < 60 ml/min, using the MDRD equation as report by the OHSU
             laboratory).

          -  Liver failure, cirrhosis, or any other liver disease that compromises liver function
             as determined by the investigator.

          -  Hematocrit of less than 36% for men, less than 32% for women.

          -  Hypertensive subjects with systolic blood pressure >= 160 mm Hg or diastolic blood
             pressure >= 100 mm Hg despite treatment or who have treatment-refractory hypertension
             (e.g. requiring four or more medications).

          -  History of severe hypoglycemia during the past 12 months prior to screening visit or
             hypoglycemia unawareness as judged by the investigator. Subjects will complete a
             hypoglycemia awareness questionnaire. Subjects will be excluded for four or more R
             responses.

          -  Adrenal insufficiency.

          -  Any active infection.

          -  Known or suspected abuse of alcohol, narcotics, or illicit drugs.

          -  Seizure disorder.

          -  Active foot ulceration.

          -  Severe peripheral arterial disease characterized by ischemic rest pain or severe
             claudication.

          -  Major surgical operation within 30 days prior to screening.

          -  Use of an investigational drug within 30 days prior to screening.

          -  Chronic usage of any immunosuppressive medication (such as cyclosporine, azathioprine,
             sirolimus, or tacrolimus).

          -  Bleeding disorder, treatment with warfarin, or platelet count below 50,000.

          -  Allergy to aspart insulin.

          -  Allergy to glucagon.

          -  Need for uninterrupted treatment of acetaminophen.

          -  Current administration of oral or parenteral corticosteroids.

          -  Any life threatening disease, including malignant neoplasms and medical history or
             malignant neoplasms within the past 5 years prior to screening (except basal and
             squamous cell skin cancer).

          -  Beta blockers or non-dihydropyridine calcium channel blockers.

          -  Current use of any medication intended to lower glucose other than insulin (e.g. use
             of liraglutide).

          -  Diagnosis of pheochromocytoma, insulinoma, or glucagonoma, personal or family history
             of multiple endocrine neoplasmia (MEN) 2A, MEN 2B, neurofibromatosis or von
             Hippel-Lindau disease.

          -  History of severe hypersensitivity to milk protein.

          -  Current use of any medication with strong anticholinergic properties, such as
             antihistamines, sleep aids, and antidiarrheal medications.

          -  Current use of indomethacin.

          -  Conditions that may results in low levels of releasable glucose in the liver and an
             inadequate reversal of hypoglycemia by glucagon such as prolonged fasting, starvation
             or chronic hypoglycemia as determined by the investigator.

          -  A positive response to any of the questions from the Physical Activity Readiness
             Questionnaire with one exception: subject will not be excluded if he/she takes a
             single blood pressure medication that doesn't impact heart rate and blood pressure is
             controlled on the medication (blood pressure is less than 140/90 mmHg).

          -  Any chest discomfort with physical activity, including pain or pressure, or other
             types of discomfort.

          -  Any clinically significant disease or disorder which in the opinion of the
             investigator may jeopardize the subject's safety or compliance with the protocol.