Hybrid Closed-Loop Control With Smart Prandial Insulin Dosing in Type 1 Diabetes

Hybrid Closed-Loop Control With Prandial Insulin Dosing Informed by Insulin Sensitivity in Adolescents With Type 1 Diabetes

The objective of this study is to evaluate the safety and feasibility of a smart bolus calculator that adjusts insulin dosing for meals according to real-time insulin sensitivity (SI) in adolescents with type 1 diabetes (T1D) using a hybrid closed loop (HCL) system during an active week of diabetes camp.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Device: Standard HCL System; Device: HCL System with Smart Bolus Calculator

Detailed Description

This is a single center, double-blind, randomized, crossover trial. The study team will target enrollment of 30 adolescents (age 12 - <18 years) with T1D who currently manage their diabetes with an insulin pump and a continuous glucose monitoring (CGM) system. Participants will be randomized 1:1 to the use of the standard HCL system (USS Virginia) vs. the HCL system with the smart bolus calculator first. The trial will be held at a local camp facility and will consist of EITHER a weeklong (6 day/5 night) camp OR two long weekends (4 day/3 night) separated by a washout period of about one week.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22902
      • University of Virginia Center for Diabetes Technology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥12 and <18 years old at time of consent
2. Clinical diagnosis, based on investigator assessment, of T1D for at least one year
3. Currently using insulin for at least six months
4. Currently using an insulin pump for at least three months
5. Currently using a CGM system for at least three months
6. Having at least 75% of CGM data over the previous four weeks
7. Using insulin parameters such as carbohydrate ratio and correction factors consistently on their pump in order to dose insulin for meals or corrections
8. Access to internet and willingness to upload data during the study as needed
9. For females, not currently known to be pregnant or breastfeeding
10. A negative urine pregnancy test will be required for all females of childbearing potential
11. Willingness to suspend use of any personal CGM for the duration of the clinical trial once the study CGM is in use
12. Willingness to switch to lispro (Humalog) or aspart (Novolog) if not using already, and to use no other insulin besides lispro (Humalog) or aspart (Novolog) during the study
13. Total daily insulin dose (TDD) of at least 10 U/day
14. Willingness not to start any non-insulin glucose-lowering agent during the course of the trial (including metformin, GLP-1 agonists, pramlintide, DPP-4 inhibitors, biguanides, sulfonylureas and naturaceuticals)
15. Willingness to eat at least 40 grams of carbohydrates per meal
16. An understanding and willingness to follow the protocol and signed informed consent
17. Participants and parent/legal guardians will be proficient in reading and writing in English
18. Willingness to comply with COVID-19 precautions as defined by the study team
19. Having completed a COVID-19 vaccination with an FDA-approved COVID-19 vaccine at least two weeks before the first study admission, and willing to provide a copy of the COVID-19 vaccination card

Exclusion Criteria:

1. Hemoglobin A1c <5% or >10% if measured at screening or available from historical medical report performed within the last 6 months; in absence of a valid HbA1c measurement, average blood glucose estimated from CGM data to be approximately between 100 and 240 mg/dL
2. History of diabetic ketoacidosis (DKA) in the 6 months prior to enrollment
3. Severe hypoglycemia resulting in seizure or loss of consciousness in the 6 months prior to enrollment
4. Pregnancy or intent to become pregnant during the trial
5. Currently breastfeeding or planning to breastfeed
6. Currently being treated for a seizure disorder
7. Planned surgery during study duration
8. History of cardiac arrhythmia (except for benign premature atrial contractions and benign premature ventricular contractions which are permitted)
9. Treatment with any non-insulin glucose-lowering agent (metformin, GLP-1 agonists, pramlintide, DPP-4 inhibitors, SGLT-2 inhibitors, biguanides, sulfonylureas and naturaceuticals)
10. A known medical condition that in the judgment of the investigator might interfere with the completion of the protocol.
11. Use of an insulin delivery mechanism that is not downloadable by the participant or study team
12. Known contact with COVID-positive individual within 14 days of any study admission without negative follow-up COVID-19 Polymerase Chain Reaction (PCR) test performed 3-5 days after the date of exposure
13. Symptoms of COVID-19 (e.g., fever, shortness of breath, unexpected loss of taste or smell) developed within 14 days of any study admission
14. A positive COVID-19 test within 14 days of any study admission or during study admission participation
15. Not being fully vaccinated at the time of the first camp admission (according to Center for Disease Control (CDC) guidelines a person is intended to be fully vaccinated after two weeks from either the second dose of the Pfizer or Moderna vaccine, or the single dose of the Johnson & Johnson vaccine)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Standard HCL System - HCL System with Smart Bolus Calculator; Use of standard HCL system followed by use of HCL system with smart bolus calculator informed by insulin sensitivity	Device: Standard HCL System; Standard HCL system (USS Virginia); Device: HCL System with Smart Bolus Calculator; HCL system (USS Virginia) with smart bolus calculator informed by insulin sensitivity
Other: HCL System with Smart Bolus Calculator - Standard HCL System; Use of HCL system with smart bolus calculator informed by insulin sensitivity followed by use of standard HCL system	Device: Standard HCL System; Standard HCL system (USS Virginia); Device: HCL System with Smart Bolus Calculator; HCL system (USS Virginia) with smart bolus calculator informed by insulin sensitivity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Low Blood Glucose Index (LBGI)	LBGI computed from CGM collected in the four hours following the dinner meal. LBGI is a metric quantifying the risk for hypoglycemia (the higher the LBGI, the higher the exposure to/risk of hypoglycemia), calculated based on the following two steps: Transforming each CGM reading in the time-series of length N into a hypoglycemia risk score (rL(i), i=1,...,N) by applying the following transformation:rL(i) = 10 x (1.509 x (log(CGM(i))^1.084 - 5.381))^2, if CGM(i) <=112.5 mg/dL; rL(i) = 0, if CGM(i) >112.5 mg/dL; Averaging the risk scores rL(i), i=1,...,N. The hypoglycemia risk score ranges from 0 for CGM readings >112.5 mg/dL (no hypoglycemia risk) to 100 for CGM readings =20 mg/dL (maximum hypoglycemia risk); consequently, LBGI can theoretically assume values between 0 and 100 as well. Clinically relevant LBGI thresholds have been defined: LBGI <2.5: low hypoglycemia risk; LBGI in 2.5-5: moderate hypoglycemia risk; LBGI >5: high hypoglycemia risk.	4 hours (dinner postprandial period); the final metric for each intervention type is obtained as the average over two consecutive camp days (days 1-2 for the first intervention; days 3-4 for the second intervention)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Time Spent Below 70 mg/dL	Percentage of CGM readings in hypoglycemia below 70 mg/dL	4 hour (dinner postprandial period); average over two consecutive days for each intervention type, as described for primary outcome
Percentage of Time Spent in 70-180 mg/dL	Percentage of CGM readings in normoglycemia between 70-180 mg/dL	4 hour (dinner postprandial period); average over two consecutive days for each intervention type, as described for primary outcome
Percentage of Time Spent Above 180 mg/dL	Percentage of CGM readings in hyperglycemia above 180 mg/dL	4 hour (dinner postprandial period); average over two consecutive days for each intervention type, as described for primary outcome
High Blood Glucose Index (HBGI)	HBGI computed from CGM collected in the four hours following the dinner meal. HBGI is a metric quantifying the risk for hyperglycemia (the higher the HBGI, the higher the exposure to/risk of hyperglycemia), calculated based on the following two steps: Transforming each CGM reading in the time-series of length N into a hyperglycemia risk score (rH(i), i=1,...,N) by applying the following transformation:rH(i) = 10 x (1.509 x (log(CGM(i))^1.084 - 5.381))^2, if CGM(i) >112.5 mg/dL; rH(i) = 0, if CGM(i) <=112.5 mg/dL; Averaging the risk scores rH(i), i=1,...,N. The hyperglycemia risk score ranges from 0 for CGM readings <=112.5 mg/dL (no hyperglycemia risk) to 100 for CGM readings =600 mg/dL (maximum hyperglycemia risk); consequently, HBGI can theoretically assume values between 0 and 100 as well. Clinically relevant HBGI thresholds have been defined: HBGI <4.5: low hyperglycemia risk; HBGI in 4.5-9: moderate hyperglycemia risk; HBGI >9: high hyperglycemia risk.	4 hour (dinner postprandial period); average over two consecutive days for each intervention type, as described for primary outcome
CGM Coefficient of Variation	CGM coefficient of variation as a measure of glucose variability	4 hour (dinner postprandial period); average over two consecutive days for each intervention type, as described for primary outcome
Total Amount of Carbohydrate Administered as Rescue Treatments	Total amount of carbohydrate administered as rescue treatments per study protocol	4 hour (dinner postprandial period); average over two consecutive days for each intervention type, as described for primary outcome

Collaborators and Investigators

• Sponsor: University of Virginia
• Collaborators: Juvenile Diabetes Research Foundation
• Investigators: Principal Investigator: Chiara Fabris, PhD, University of Virginia Center for Diabetes Technology

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2021
• Primary Completion (Actual): June 24, 2022
• Study Completion (Actual): June 28, 2022

Study Registration Dates

• First Submitted: May 4, 2021
• First Submitted That Met QC Criteria: May 6, 2021
• First Posted (Actual): May 7, 2021

Study Record Updates

• Last Update Posted (Actual): May 30, 2024
• Last Update Submitted That Met QC Criteria: May 2, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Adolescent; Continuous Glucose Monitor (CGM); Insulin Pump; Insulin Sensitivity (SI); Hybrid Closed Loop (HCL); Diabetes Camp
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: 210112; 4-CDA-2020-948-A-N (Other Grant/Funding Number: JDRF International (JDRF))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes