Bionic Pancreas in Children With Hyperinsulinism and Post-Pancreatectomy Diabetes

• Sponsor: Children's Hospital of Philadelphia (Other)
• Overall Status: Completed
• CT.gov ID: NCT03303196
• Collaborator: Boston University (Other), Massachusetts General Hospital (Other)
• Enrollment: 10
• Location: 1
• Arms: 2
• Actual Duration (Months): 17.7
• Patients Per Site Per Month: 0.6

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Hyperinsulinism; Diabetes; Pancreatic Diseases; Pancreatectomy; Hyperglycemia	Device: Bihormonal Bionic Pancreas	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• 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.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)
• Primary Purpose: Treatment
• Official Title: Bihormonal Bionic Pancreas for the Treatment of Diabetes Post-Pancreatectomy in Children With Congenital Hyperinsulinism - A Pilot Study
• Actual Study Start Date: Apr 9, 2018
• Actual Primary Completion Date: Sep 30, 2019
• Actual Study Completion Date: Sep 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	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.
No Intervention: 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.

Outcome Measures

Primary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 30 Years
• Sexes Eligible for Study: All
• Accepts 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.

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

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

3. 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).

4. 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.

5. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• Children's Hospital of Philadelphia
• Boston University
• Massachusetts General Hospital

Investigators

• Principal Investigator: Diva D De Leon, MD, MSCE, Children's Hospital of Philadelphia
• Principal Investigator: Arpana Rayannavar, MD, Children's Hospital of Philadelphia

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 22, 2018

More Information

Additional Information:

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

Publications

• 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.
• 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.
• 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.
• 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.
• 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.

• Responsible Party: Diva De Leon, MD, MSCE, Director, Congenital Hyperinsulinism Center, Children's Hospital of Philadelphia
• ClinicalTrials.gov Identifier: NCT03303196
• Other Study ID Numbers: 17-014144
• First Posted: Oct 5, 2017
• Last Update Posted: Oct 27, 2020
• Last Verified: Oct 1, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Keywords provided by Diva De Leon, MD, MSCE, Director, Congenital Hyperinsulinism Center, Children's Hospital of Philadelphia: Post-Pancreatectomy Diabetes; Insulin Therapy
• Additional relevant MeSH terms: Pancreatic Diseases; Diabetes Mellitus; Hyperglycemia; Hyperinsulinism; Pancrelipase

Study Results

Participant Flow

Arm/Group Title	Bihormonal Bionic Pancreas Admission	Standard Care Admission
Arm/Group 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.
Period Title: Overall Study
STARTED	5	5
Washout	5	5
COMPLETED	5	5
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Sequential Admissions
Arm/Group Description	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.
Overall Participants	10
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	15.1
Sex: Female, Male (Count of Participants)
Female	5 50%
Male	5 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	10 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 10%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	9 90%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	10 100%
Mean Plasma Glucose Level (mmmol/L) [Mean (Standard Deviation) ]
Bionic Pancreas Admission	8.3 (0.7)
Standard Care Admission	9.0 (1.8)

Outcome Measures

1. Primary Outcome

Title	Mean Plasma Glucose Level.
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sequential Admissions
Arm/Group Description	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.
Measure Participants	10
Bihormonal Bionic Pancreas Admission	149.666118 (12.7998623)
Standard Care Admision	162.574753 (32.2642656)

Adverse Events

Time Frame	Adverse event data was collected from the start of screening until the end of the last day of the subject's second admission. This time period ranged from 16 to 38 days, depending on how many days in between admissions they had.
Arm/Group Title	Bihormonal Bionic Pancreas Admission		Standard Care Admission
Arm/Group 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.
All Cause Mortality
	Bihormonal Bionic Pancreas Admission		Standard Care Admission
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)
Serious Adverse Events
	Bihormonal Bionic Pancreas Admission		Standard Care Admission
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Bihormonal Bionic Pancreas Admission		Standard Care Admission
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/5 (40%)		5/5 (100%)
Gastrointestinal disorders
Intermittent nasuea	2/5 (40%)	3	3/5 (60%)	4
Infections and infestations
Upper respiratory infection	0/5 (0%)	0	1/5 (20%)	1
Metabolism and nutrition disorders
Hyperglycemia	0/5 (0%)	0	1/5 (20%)	1
Nervous system disorders
Headache	0/5 (0%)	0	3/5 (60%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.