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

Study Overview
=================
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.

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

Conditions
-----------------
Type 1 Diabetes

Intervention / Treatment
-----------------
* Device: Hybrid Closed Loop Control (USS Virginia) with Smart Bolus Calculator Informed by SI
* Device: Standard Hybrid Closed Loop Control (USS Virginia)


Participation Criteria
=================
Eligibility Criteria
-----------------
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)

Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard Hybrid Closed Loop Control (USS Virginia)<br>Use of Standard Hybrid Closed Loop Control | Device: Standard Hybrid Closed Loop Control (USS Virginia)<br>* Standard Hybrid Closed Loop Control (USS Virginia)<br>|
| Experimental: Hybrid Closed Loop Control (USS Virginia) with Smart Bolus Calculator Informed by SI<br>Use of Hybrid Closed Loop Control with Enhanced Prandial Dosing | Device: Hybrid Closed Loop Control (USS Virginia) with Smart Bolus Calculator Informed by SI<br>* Hybrid Closed Loop Control (USS Virginia) with Smart Bolus Calculator Informed by SI<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Low blood glucose index (LBGI) | Low blood glucose index (LBGI) computed from CGM collected in the four hours following the dinner meal | 1 day (Dinner postprandial) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of time spent below 70 mg/dL | Percentage of time spent below 70 mg/dL | 1 day (Dinner postprandial, daytime, nighttime, whole day) | 
| Percentage of time spent in 70-140 and 70-180 mg/dL | Percentage of time spent in 70-140 and 70-180 mg/dL | 1 day (Dinner postprandial, daytime, nighttime, whole day) | 
| Percentage of time spent above 180 and 250 mg/dL | Percentage of time spent above 180 and 250 mg/dL | 1 day (Dinner postprandial, daytime, nighttime, whole day) | 
| High blood glucose index | High blood glucose index | 1 day (Dinner postprandial, daytime, nighttime, whole day) | 
| CGM coefficient of variation | CGM coefficient of variation | 1 day (Dinner postprandial, daytime, nighttime, whole day) | 
| Total number and amount of carbohydrate administered as rescue treatments | Total number and amount of carbohydrate administered as rescue treatments | 1 day (Dinner postprandial, daytime, nighttime, whole day) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Insulin Sensitivity (SI), Adolescent, Insulin Pump, Continuous Glucose Monitor (CGM), Hybrid Closed Loop (HCL), Diabetes Camp