Two Way Crossover Closed Loop Study Insulin vs Insulin and Pramlintide

Prior treatment

• History of severe hypoglycemia during the past 3 months prior to screening visit or hypoglycemia unawareness as judged by the investigator. Participants will complete a hypoglycemia awareness questionnaire. Participants will be excluded for four or more R responses.
• History of diabetes ketoacidosis during the prior 3 months prior to screening visit, as diagnosed on hospital admission or as judged by the investigator.
• Known or suspected abuse of alcohol, narcotics, or illicit drugs.
• 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).
• Current administration of oral or parenteral corticosteroids.

Other illness

• 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 or 3rd degree heart block or any non-physiological arrhythmia judged by the investigator to be exclusionary.
• Liver failure, cirrhosis, or any other liver disease that compromises liver function as determined by the investigator.
• Adrenal insufficiency.
• Any active infection requiring treatment (example soft tissue infection requiring antibiotics).
• Seizure disorder.
• Allergy to aspart insulin.
• Allergy to pramlintide.
• Any life-threatening disease, including malignant neoplasms and medical history of malignant neoplasms within the past 5 years prior to screening (except basal and squamous cell skin cancer).
• Dietary restrictions or allergies to the study meals
• Any clinically significant disease or disorder which in the opinion of the Investigator may jeopardize the participant's safety or compliance with the protocol.

Lab values

• Renal insufficiency (GFR \< 60 ml/min, using the MDRD equation as reported by the OHSU laboratory).
• Bleeding disorder, treatment with warfarin, or platelet count below 50,000.
• Current use of any medication intended to lower glucose other than insulin or pramlintide (ex. use of liraglutide, metformin).

Other

• Individual 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.
• Active foot ulceration.
• Gastroparesis
• Diets consisting of less than 50 grams of carbohydrates per day.

• Diagnosis of type 1 diabetes mellitus for at least 1 year.
• Participants 18 to 70 years of age.
• Current use of an insulin pump for at least 3 months with stable insulin pump settings for \>2 weeks OR current use of multiple day injection insulin therapy with stable doses for \>2 weeks.
• Uses a carbohydrate ratio, at lease occasionally, to dose meal time insulin.
• HbA1c ≤ 10.5% at screening.
• Total daily insulin requirement is less than 139 units/day.
• Willingness to follow all study procedures, including attending all clinic visits.
• Willingness to sign informed consent and HIPAA documents.