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Bionic Pancreas in Children With Hyperinsulinism and Post-Pancreatectomy Diabetes

Primary Purpose

Hyperinsulinism, Diabetes, Pancreatic Diseases

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Bihormonal Bionic Pancreas

About this trial

This is an interventional treatment trial for Hyperinsulinism focused on measuring Post-Pancreatectomy Diabetes, Insulin Therapy

Eligibility Criteria

6 Years - 30 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Males or females age 6 to 30 years.
Diagnosis of hyperinsulinism.
Previous pancreatectomy.
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.
On insulin therapy with a regimen of at least 11 units/kg/day.
Treatment with subcutaneous insulin by pump at the time of recruitment.
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).
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.
Informed consent, parental/guardian permission (informed consent) and if appropriate, child assent.

Exclusion Criteria:

Unable to provide informed consent (e.g. impaired cognition or judgment).
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.
Evidence of severe hematologic abnormality including severe anemia and/or thrombocytopenia.
Electrically powered implants (e.g. cochlear implants, neurostimulators) that might be susceptible to radio frequency interference.
Unable to completely avoid acetaminophen for duration of study.
History of adverse reaction to glucagon (including allergy) besides nausea and vomiting.
Established history of allergy or severe reaction to adhesive or tape that must be used in the study.
Use oral (e.g. thiazolidinediones, biguanides, sulfonylureas, glitinides, dipeptidyl peptidase-4 (DPP-4) inhibitors, Sodium-glucose Cotransporter-2 (SGLT-2) inhibitors anti-diabetic medications.
Any investigational drug use within 30 days prior to enrollment.
Pregnant or lactating females.
Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.

Sites / Locations

Children's Hospital of Philadelphia

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Bihormonal bionic pancreas admission

Standard care admission

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT03303196

First Posted

October 2, 2017

Last Updated

October 2, 2020

Sponsor

Children's Hospital of Philadelphia

Collaborators

Boston University, Massachusetts General Hospital

1. Study Identification

Unique Protocol Identification Number

NCT03303196

Brief Title

Bionic Pancreas in Children With Hyperinsulinism and Post-Pancreatectomy Diabetes

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2020

Overall Recruitment Status

Completed

Study Start Date

April 9, 2018 (Actual)

Primary Completion Date

September 30, 2019 (Actual)

Study Completion Date

September 30, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Children's Hospital of Philadelphia

Collaborators

Boston University, Massachusetts General Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Device Product Not Approved or Cleared by U.S. FDA

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hyperinsulinism, Diabetes, Pancreatic Diseases, Pancreatectomy; Hyperglycemia

Keywords

Post-Pancreatectomy Diabetes, Insulin Therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

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.

Masking

None (Open Label)

Allocation

Randomized

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Bihormonal bionic pancreas admission

Arm Type

Experimental

Arm Description

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.

Arm Title

Standard care admission

Arm Type

No Intervention

Arm Description

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.

Intervention Type

Device

Intervention Name(s)

Bihormonal Bionic Pancreas

Intervention Description

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.

Primary Outcome Measure Information:

Title

Mean Plasma Glucose Level.

Description

Time Frame

Days 2-3 of each admission

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Years

Maximum Age & Unit of Time

30 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Males or females age 6 to 30 years. Diagnosis of hyperinsulinism. Previous pancreatectomy. 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. On insulin therapy with a regimen of at least 11 units/kg/day. Treatment with subcutaneous insulin by pump at the time of recruitment. 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). 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. Informed consent, parental/guardian permission (informed consent) and if appropriate, child assent. Exclusion Criteria: Unable to provide informed consent (e.g. impaired cognition or judgment). 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. Evidence of severe hematologic abnormality including severe anemia and/or thrombocytopenia. Electrically powered implants (e.g. cochlear implants, neurostimulators) that might be susceptible to radio frequency interference. Unable to completely avoid acetaminophen for duration of study. History of adverse reaction to glucagon (including allergy) besides nausea and vomiting. Established history of allergy or severe reaction to adhesive or tape that must be used in the study. Use oral (e.g. thiazolidinediones, biguanides, sulfonylureas, glitinides, dipeptidyl peptidase-4 (DPP-4) inhibitors, Sodium-glucose Cotransporter-2 (SGLT-2) inhibitors anti-diabetic medications. Any investigational drug use within 30 days prior to enrollment. Pregnant or lactating females. Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Diva D De Leon, MD, MSCE

Organizational Affiliation

Children's Hospital of Philadelphia

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Arpana Rayannavar, MD

Organizational Affiliation

Children's Hospital of Philadelphia

Official's Role

Principal Investigator

Facility Information:

Facility Name

Children's Hospital of Philadelphia

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

22923666

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.

Results Reference

background

PubMed Identifier

24483160

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.

Results Reference

background

PubMed Identifier

26850709

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.

Results Reference

background

PubMed Identifier

28007348

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.

Results Reference

background

PubMed Identifier

17179930

Citation

De Leon 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. doi: 10.1038/ncpendmet0368.

Results Reference

background

PubMed Identifier

34518377

Citation

Rayannavar A, Mitteer LM, Balliro CA, El-Khatib FH, Lord KL, Hawkes CP, Ballester LS, Damiano ER, Russell SJ, De Leon DD. The Bihormonal Bionic Pancreas Improves Glycemic Control in Individuals With Hyperinsulinism and Postpancreatectomy Diabetes: A Pilot Study. Diabetes Care. 2021 Nov;44(11):2582-2585. doi: 10.2337/dc21-0416. Epub 2021 Sep 13.

Results Reference

derived

Links:

URL

http://www.chop.edu/centers-programs/congenital-hyperinsulinism-center

Description

Children's Hospital of Philadelphia | Congenital Hyperinsulinism Center Website

URL

http://www.artificialpancreas.org/

Description

Boston University | Bionic Pancreas Website

Learn more about this trial

Bionic Pancreas in Children With Hyperinsulinism and Post-Pancreatectomy Diabetes

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