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

Not Applicable

Completed

Conditions: Type 1 Diabetes

Interventions: Device: Standard HCL System
Device: HCL System with Smart Bolus Calculator

Registration Number: NCT04878120

Lead Sponsor: University of Virginia

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 25

Inclusion Criteria

Age ≥12 and <18 years old at time of consent
Clinical diagnosis, based on investigator assessment, of T1D for at least one year
Currently using insulin for at least six months
Currently using an insulin pump for at least three months
Currently using a CGM system for at least three months
Having at least 75% of CGM data over the previous four weeks
Using insulin parameters such as carbohydrate ratio and correction factors consistently on their pump in order to dose insulin for meals or corrections
Access to internet and willingness to upload data during the study as needed
For females, not currently known to be pregnant or breastfeeding
A negative urine pregnancy test will be required for all females of childbearing potential
Willingness to suspend use of any personal CGM for the duration of the clinical trial once the study CGM is in use
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
Total daily insulin dose (TDD) of at least 10 U/day
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)
Willingness to eat at least 40 grams of carbohydrates per meal
An understanding and willingness to follow the protocol and signed informed consent
Participants and parent/legal guardians will be proficient in reading and writing in English
Willingness to comply with COVID-19 precautions as defined by the study team
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

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
History of diabetic ketoacidosis (DKA) in the 6 months prior to enrollment
Severe hypoglycemia resulting in seizure or loss of consciousness in the 6 months prior to enrollment
Pregnancy or intent to become pregnant during the trial
Currently breastfeeding or planning to breastfeed
Currently being treated for a seizure disorder
Planned surgery during study duration
History of cardiac arrhythmia (except for benign premature atrial contractions and benign premature ventricular contractions which are permitted)
Treatment with any non-insulin glucose-lowering agent (metformin, GLP-1 agonists, pramlintide, DPP-4 inhibitors, SGLT-2 inhibitors, biguanides, sulfonylureas and naturaceuticals)
A known medical condition that in the judgment of the investigator might interfere with the completion of the protocol.
Use of an insulin delivery mechanism that is not downloadable by the participant or study team
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
Symptoms of COVID-19 (e.g., fever, shortness of breath, unexpected loss of taste or smell) developed within 14 days of any study admission
A positive COVID-19 test within 14 days of any study admission or during study admission participation
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 & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Standard HCL System - HCL System with Smart Bolus Calculator	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
HCL System with Smart Bolus Calculator - Standard HCL System	HCL System with Smart Bolus Calculator	Use of HCL system with smart bolus calculator informed by insulin sensitivity followed by use of standard HCL system
Standard HCL System - HCL System with Smart Bolus Calculator	Standard HCL System	Use of standard HCL system followed by use of HCL system with smart bolus calculator informed by insulin sensitivity
HCL System with Smart Bolus Calculator - Standard HCL System	Standard HCL System	Use of HCL system with smart bolus calculator informed by insulin sensitivity followed by use of standard HCL system

Primary Outcome Measures

Name	Time	Method
Low Blood Glucose Index (LBGI)	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)	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: 1. 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 2. 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: 1. LBGI \<2.5: low hypoglycemia risk 2. LBGI in 2.5-5: moderate hypoglycemia risk 3. LBGI \>5: high hypoglycemia risk.

Secondary Outcome Measures

Name	Time	Method
Percentage of Time Spent in 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 CGM readings in normoglycemia between 70-180 mg/dL
Percentage of Time Spent 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 CGM readings in hypoglycemia below 70 mg/dL
Percentage of Time Spent Above 180 mg/dL	4 hour (dinner postprandial period); average over two consecutive days for each intervention type, as described for primary outcome	Percentage of CGM readings in hyperglycemia above 180 mg/dL
CGM Coefficient of Variation	4 hour (dinner postprandial period); average over two consecutive days for each intervention type, as described for primary outcome	CGM coefficient of variation as a measure of glucose variability
Total Amount of Carbohydrate Administered as Rescue Treatments	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 per study protocol
High Blood Glucose Index (HBGI)	4 hour (dinner postprandial period); average over two consecutive days for each intervention type, as described for primary outcome	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: 1. 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 2. 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: 1. HBGI \<4.5: low hyperglycemia risk 2. HBGI in 4.5-9: moderate hyperglycemia risk 3. HBGI \>9: high hyperglycemia risk.