Effect of Exendin (9-39) on Glucose Requirements to Maintain Euglycemia
Congenital Hyperinsulinism
About this trial
This is an interventional treatment trial for Congenital Hyperinsulinism focused on measuring Congenital Hyperinsulinism, Hyperinsulinism, Hypoglycemia, KATP channel, Metabolic Diseases, Pancreatic Disease, Glucose Metabolism Disorders, Infant, Newborn, Diseases
Eligibility Criteria
Inclusion Criteria:
- Confirmed clinical diagnosis of congenital hyperinsulinism
- Infants less than 12 months of age at study enrollment
- Failure to respond to treatment with diazoxide
Exclusion Criteria:
- Evidence of a medical condition that might alter results, including kidney failure, severe liver dysfunction, severe respiratory or cardiac failure
Treatment with medications that may affect glucose metabolism at the time of initiation of study procedures, including:
- Treatment with glucagon 4 hours prior to infusion (T=0)
- Treatment with octreotide 24 hours prior to infusion (T=0)
- Treatment with diazoxide 72 hours prior to infusion (T=0)
- Suspected Beckwith-Wiedemann syndrome or other syndromic forms of congenital hyperinsulinism.
Sites / Locations
- The Children's Hospital of Philadelphia
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Experimental
Experimental
Exendin (9-39) 0.02 mg/kg/hr
Exendin (9-39) 0.04 mg/kg/hr
Exendin (9-39) 0.10 mg/kg/hr
Exendin (9-39) 0.20 mg/kg/hr
Cohort 1: Participants will be administered 0.02 mg/kg/hr of Exendin (9-39) and vehicle (normal saline), via continuous intravenous infusion, over 9 hours on two separate days in random order, with 3 hours of follow-up after the last dose is administered or until blood glucose is < 70 mg/dL (whichever comes first). Glucose infusion rates (GIR) will be titrated three hours prior to infusions to keep blood glucose in the range of 70-90 mg/dL. During both infusions, blood glucose will be measured every 30 minutes.
Cohort 2: Participants will be administered 0.04 mg/kg/hr of Exendin (9-39) and vehicle (normal saline), via continuous intravenous infusion, over 9 hours on two separate days in random order, with 3 hours of follow-up after the last dose is administered or until blood glucose is < 70 mg/dL (whichever comes first). Glucose infusion rates (GIR) will be titrated three hours prior to infusions to keep blood glucose in the range of 70-90 mg/dL. During both infusions, blood glucose will be measured every 30 minutes.
Cohort 3: Participants will be administered 0.10 mg/kg/hr of Exendin (9-39) and vehicle (normal saline), via continuous intravenous infusion, over 6 hours on two separate days in random order, with 3 hours of follow-up after the last dose is administered or until blood glucose is < 70 mg/dL (whichever comes first). Glucose infusion rates (GIR) will be titrated three hours prior to infusions to keep blood glucose in the range of 70-90 mg/dL. During both infusions, blood glucose will be measured every 30 minutes.
Cohort 4: Participants will be administered 0.20 mg/kg/hr of Exendin (9-39) and vehicle (normal saline), via continuous intravenous infusion, over 9 hours on two separate days in random order, with 3 hours of follow-up after the last dose is administered or until blood glucose is < 70 mg/dL (whichever comes first). Glucose infusion rates (GIR) will be titrated three hours prior to infusions to keep blood glucose in the range of 70-90 mg/dL. During both infusions, blood glucose will be measured every 30 minutes.