This study will enroll infants with congenital hyperinsulinism owing to KATP channel mutations who are unresponsive to medical therapy and will require a pancreatectomy to control hypoglycemia from a single academic medical center in the United States.~An open-label, two-period, two-treatment crossover study design with a dose-escalation component will be implemented. Successive cohorts of patients (up to 5 participants/cohort) will each receive a fixed dose of Exendin (9-39) infusion and normal saline vehicle on two separate days in random order. The protocol specifies 0.02 mg/kg/hr, via continuous intravenous infusion, administered over 9-hours for the first cohort. The volume of saline to be infused will be calculated to match the volume of Exendin (9-39). Successive cohorts will be given doses that are increased in up to 1/2 log increments. Overall, the investigators hypothesize that antagonism of the GLP-1 receptor by Exendin (9-39) will increase fasting blood glucose levels, prevent protein-induced hypoglycemia and decrease glucose requirement to maintain euglycemia in infants with CHI.~Aim 1. To examine the effect of Exendin (9-39) on glucose requirements to maintain euglycemia in infants with congenital hyperinsulinism unresponsive to medical therapy.~Aim 2. To determine therapeutic plasma levels, plasma half-life and pharmacokinetics of Exendin-(9-39) during an intravenous infusion.
The primary aim of this study is to evaluate the effect of Exendin (9-39) on glucose requirements to maintain euglycemia in pediatric patients with congenital hyperinsulinism (CHI) who have failed medical therapy. The secondary aims are to determine the therapeutic plasma levels, plasma half-life and pharmacokinetics of Exendin (9-39) during a 9-hour intravenous infusion.