Bionic Pancreas in Children With Hyperinsulinism and Post-Pancreatectomy Diabetes

NCT ID: NCT03303196

Last Updated: 2020-10-27

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-04-09

Study Completion Date

2019-09-30

Brief Summary

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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

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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.

Conditions

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Hyperinsulinism Diabetes Pancreatic Diseases Pancreatectomy; Hyperglycemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Bihormonal Bionic Pancreas

Intervention Type DEVICE

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.

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.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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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.

Intervention Type DEVICE

Eligibility Criteria

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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.
Minimum Eligible Age

6 Years

Maximum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Boston University

OTHER

Sponsor Role collaborator

Massachusetts General Hospital

OTHER

Sponsor Role collaborator

Children's Hospital of Philadelphia

OTHER

Sponsor Role lead

Responsible Party

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Diva De Leon, MD, MSCE

Director, Congenital Hyperinsulinism Center

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Diva D De Leon, MD, MSCE

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Arpana Rayannavar, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Locations

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Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 22923666 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24483160 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26850709 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28007348 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17179930 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34518377 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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

Children's Hospital of Philadelphia \| Congenital Hyperinsulinism Center Website

http://www.artificialpancreas.org/

Boston University \| Bionic Pancreas Website

Other Identifiers

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17-014144

Identifier Type: -

Identifier Source: org_study_id