Bionic Pancreas in Children With Hyperinsulinism and Post-Pancreatectomy Diabetes

The management of diabetes following pancreatectomy for hyperinsulinism (HI) generally
consists of the same approaches that are used for individuals with type 1 diabetes (T1D).
However, there are significant differences in individuals with HI and post-pancreatectomy
diabetes that increases the risk of hypoglycemia in these individuals and prevent achieving
tight glycemic control. Individuals with HI have glucagon deficiency and unlike T1D, those
with HI and post-pancreatectomy diabetes have residual dysregulated insulin secretion that
results in marked hypo- and hyper-glycemia. Furthermore, pancreatic insufficiency can result
in disturbances in nutrient absorption and fluctuations in glucose concentrations.

Current treatment approaches with intermittent subcutaneous insulin administration or insulin
pump therapy offer inadequate glycemic control in these individuals. We propose a novel
approach to the management of these individuals with the bihormonal bionic pancreas to
replace both hormones, insulin and glucagon, through an automated glycemic management system.

Inclusion Criteria:

1. Males or females age 6 to 30 years.

2. Diagnosis of hyperinsulinism.

3. Previous pancreatectomy.

4. Diabetes confirmed by one or more of the following:

- Glycosylated A1c > 6.4%.

- Fasting glucose > 125 mg/dL.

- 2-hour post-prandial glucose > 200 mg/dL.

- Random glucose > 200 mg/dL with symptomatic hyperglycemia.

5. On insulin therapy with a regimen of at least 11 units/kg/day.

6. Treatment with subcutaneous insulin by pump at the time of recruitment.

7. Prescription medication regimen stable for > 1 month (except for medications that will
not affect the safety of the study and are not expected to affect any outcome of the
study, in the judgment of the site PI).

8. Females > 11 years of age must have a negative urine/serum pregnancy test and must use
an acceptable method of contraception, including abstinence, a barrier method
(diaphragm or condom), Depo-Provera, or an oral contraceptive, for the duration of the
study.

9. Informed consent, parental/guardian permission (informed consent) and if appropriate,
child assent.

Exclusion Criteria:

1. Unable to provide informed consent (e.g. impaired cognition or judgment).

2. Evidence of a medical condition that might alter results or compromise the
interpretation of results, including active infection, kidney failure, severe liver
dysfunction, severe respiratory or cardiac failure.

3. Evidence of severe hematologic abnormality including severe anemia and/or
thrombocytopenia.

4. Electrically powered implants (e.g. cochlear implants, neurostimulators) that might be
susceptible to radio frequency interference.

5. Unable to completely avoid acetaminophen for duration of study.

6. History of adverse reaction to glucagon (including allergy) besides nausea and
vomiting.

7. Established history of allergy or severe reaction to adhesive or tape that must be
used in the study.

8. Use oral (e.g. thiazolidinediones, biguanides, sulfonylureas, glitinides, dipeptidyl
peptidase-4 (DPP-4) inhibitors, Sodium-glucose Cotransporter-2 (SGLT-2) inhibitors
anti-diabetic medications.

9. Any investigational drug use within 30 days prior to enrollment.

10. Pregnant or lactating females.

11. Parents/guardians or subjects who, in the opinion of the Investigator, may be
non-compliant with study schedules or procedures.