Closed-Loop Glucagon Pump for Treatment of Post-Bariatric Hypoglycemia

Inclusion Criteria

• Males or females diagnosed with ongoing post-bariatric hypoglycemia with prior episodes of neuroglycopenia, unresponsive to dietary intervention (low glycemic index, controlled carbohydrate portions) and trial of acarbose therapy at the maximally tolerated dose.
• Age 18-65 years of age, inclusive, at screening.
• Willingness to provide informed consent and follow all study procedures, including attending all scheduled visits.

Exclusion Criteria

• Documented hypoglycemia occurring in the fasting state (> 12 hours fast);
• Chronic kidney disease stage 4 or 5 (including end-stage renal disease);
• Hepatic disease, including serum alanine transaminase (ALT) or aspartate aminotransferase (AST) greater than or equal to 3 times the upper limit of normal; hepatic synthetic insufficiency as defined as serum albumin 2.0;
• Congestive heart failure, New York Heart Association (NYHA )class II, III or IV;
• History of myocardial infarction, unstable angina or revascularization within the past 6 months or 2 or more risk factors for coronary artery disease including diabetes, uncontrolled hypertension, uncontrolled hyperlipidemia, and active tobacco use;
• History of cardiac arrhythmia or arrhythmia detected by EKG during the screening visit;
• History of syncope (unrelated to hypoglycemia) or diagnosed cardiac arrhythmia
• Concurrent administration of β-blocker therapy;
• History of a cerebrovascular accident;
• Seizure disorder (other than with suspect or documented hypoglycemia);
• Active treatment with any diabetes medications except for acarbose;
• Active malignancy, except basal cell or squamous cell skin cancers;
• Personal or family history of pheochromocytoma or disorder with increased risk of pheochromocytoma (MEN 2, neurofibromatosis, or Von Hippel-Lindau disease);
• Known insulinoma or glucagonoma;
• Major surgical operation within 30 days prior to screening;
• Hematocrit < 33%;
• Bleeding disorder, treatment with warfarin, or platelet count <50,000;
• Blood donation (1 pint of whole blood) within the past 2 months;
• Active alcohol abuse or substance abuse;
• Current administration of oral or parenteral corticosteroids;
• Pregnancy and/ or Lactation: For women of childbearing potential: there is a requirement for a negative urine pregnancy test and for agreement to use contraception during the study and for at least 1 month after participating in the study. Acceptable contraception includes birth control pill / patch / vaginal ring, Depo-Provera, Norplant, an intrauterine device (IUD), the double barrier method (the woman uses a diaphragm and spermicide and the man uses a condom), or abstinence;
• Use of an investigational drug within 30 days prior to screening;
• Current use of anticholinergic medications;
• Allergy to a component of the study drug.