Diabetes, Hyperinsulinism, Pancreatectomy; Hyperglycemia, Pancreatic Diseases
Conditions
Keywords
Post-Pancreatectomy Diabetes, Insulin Therapy
Brief summary
This is a pilot study designed to determine if the bihormonal bionic pancreas provides improved blood glucose control, compared to the current standard of care, in individuals with hyperinsulinism who developed diabetes after having a pancreatectomy.
Detailed description
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.
Interventions
A 4-day inpatient admission in which subjects will wear the bihormonal pancreas. The bihormonal pancreas will be placed upon admission and there will be 1 day of run-in. This will be followed by 3 days of data collection for comparison with the data obtained from the standard of care during the control admission.
Sponsors
Boston University
Massachusetts General Hospital
Children's Hospital of Philadelphia
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This will be an open-label, pilot clinical trial to assess efficacy and safety of the bihormonal bionic pancreas in children and young adults with HI who have developed post-pancreatectomy diabetes. Subjects will be studied during two research inpatient admissions at the CHOP HI Center. The order of the interventions will be randomized.
Eligibility
Sex/Gender
ALL
Age
6 Years to 30 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Plasma Glucose Level. | Days 2-3 of each admission | Mean plasma glucose concentration, as measured by the Continuous glucose monitoring system (CGMS), during the final 2 days of the Bihormonal Bionic Pancreas Admission compared to the Standard Care Admission. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sequential Admissions Bihormonal bionic pancreas admission: Four day inpatient admission where participants will have blood sugar managed by the Bihormonal Bionic Pancreas. Blood sugars will be monitored for safety by study staff.
\*before or after\* Standard care admission: Four day inpatient admission where participants will have blood sugar managed by the participant's home-glucose control regimen. Blood sugars will be monitored for safety by study staff. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Sequential Admissions |
|---|---|
| Age, Continuous | 15.1 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Mean Plasma Glucose Level Bionic Pancreas Admission | 8.3 mmmol/L STANDARD_DEVIATION 0.7 |
| Mean Plasma Glucose Level Standard Care Admission | 9.0 mmmol/L STANDARD_DEVIATION 1.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 5 |
| other Total, other adverse events | 2 / 5 | 5 / 5 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 |
Outcome results
Primary
Mean Plasma Glucose Level.
Mean plasma glucose concentration, as measured by the Continuous glucose monitoring system (CGMS), during the final 2 days of the Bihormonal Bionic Pancreas Admission compared to the Standard Care Admission.
Time frame: Days 2-3 of each admission
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sequential Admissions | Mean Plasma Glucose Level. | Bihormonal Bionic Pancreas Admission | 149.666118 mg/dL | Standard Deviation 12.7998623 |
| Sequential Admissions | Mean Plasma Glucose Level. | Standard Care Admision | 162.574753 mg/dL | Standard Deviation 32.2642656 |