Bionic Pancreas in Children With Hyperinsulinism and Post-Pancreatectomy Diabetes

Diabetes Clinical Trial

Official title:

Bihormonal Bionic Pancreas for the Treatment of Diabetes Post-Pancreatectomy in Children With Congenital Hyperinsulinism - A Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03303196
• Other study ID #: 17-014144
• Status: Completed
• Phase: N/A
• Start date: April 9, 2018
• Est. completion date: September 30, 2019

Study information

• Verified date: October 2020
• Source: Children's Hospital of Philadelphia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: September 30, 2019
• Est. primary completion date: September 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 30 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Hyperglycemia
• Hyperinsulinism
• Pancreatectomy; Hyperglycemia
• Pancreatic Diseases

Intervention

Device:
• Bihormonal Bionic Pancreas
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.

Locations

Country	Name	City	State
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Children's Hospital of Philadelphia	Boston University, Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

References & Publications (5)

De León DD, Stanley CA. Mechanisms of Disease: advances in diagnosis and treatment of hyperinsulinism in neonates. Nat Clin Pract Endocrinol Metab. 2007 Jan;3(1):57-68. Review. — View Citation

El-Khatib FH, Balliro C, Hillard MA, Magyar KL, Ekhlaspour L, Sinha M, Mondesir D, Esmaeili A, Hartigan C, Thompson MJ, Malkani S, Lock JP, Harlan DM, Clinton P, Frank E, Wilson DM, DeSalvo D, Norlander L, Ly T, Buckingham BA, Diner J, Dezube M, Young LA, Goley A, Kirkman MS, Buse JB, Zheng H, Selagamsetty RR, Damiano ER, Russell SJ. Home use of a bihormonal bionic pancreas versus insulin pump therapy in adults with type 1 diabetes: a multicentre randomised crossover trial. Lancet. 2017 Jan 28;389(10067):369-380. doi: 10.1016/S0140-6736(16)32567-3. Epub 2016 Dec 20. Erratum in: Lancet. 2017 Jan 28;389(10067):368. Lancet. 2017 Feb 4;389(10068):e2. — View Citation

El-Khatib FH, Russell SJ, Magyar KL, Sinha M, McKeon K, Nathan DM, Damiano ER. Autonomous and continuous adaptation of a bihormonal bionic pancreas in adults and adolescents with type 1 diabetes. J Clin Endocrinol Metab. 2014 May;99(5):1701-11. doi: 10.1210/jc.2013-4151. Epub 2014 Jan 31. — View Citation

Russell SJ, El-Khatib FH, Nathan DM, Magyar KL, Jiang J, Damiano ER. Blood glucose control in type 1 diabetes with a bihormonal bionic endocrine pancreas. Diabetes Care. 2012 Nov;35(11):2148-55. doi: 10.2337/dc12-0071. Epub 2012 Aug 24. — View Citation

Russell SJ, Hillard MA, Balliro C, Magyar KL, Selagamsetty R, Sinha M, Grennan K, Mondesir D, Ekhlaspour L, Zheng H, Damiano ER, El-Khatib FH. Day and night glycaemic control with a bionic pancreas versus conventional insulin pump therapy in preadolescent children with type 1 diabetes: a randomised crossover trial. Lancet Diabetes Endocrinol. 2016 Mar;4(3):233-243. doi: 10.1016/S2213-8587(15)00489-1. Epub 2016 Feb 3. Erratum in: Lancet Diabetes Endocrinol. 2018 Mar;6(3):e3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Days 2-3 of each admission

External Links

•   Boston University | Bionic Pancreas Website
•   Children's Hospital of Philadelphia | Congenital Hyperinsulinism Center Website