Extended Bolus for Meals in a Closed-loop System

Study Overview
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Brief Summary
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This study aims to evaluate whether the use of an extended bolus will improve glucose control with high-fat high protein meals using a closed-loop system. The new knowledge gained from this study may provide a method to allow for the proper administration of insulin over an extended period to mitigate the risk of prolonged hyperglycemia or early hypoglycemia.

Official Title
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Postprandial Glucose Control Using an Extended Bolus for High-fat High Protein Meals in a Closed-loop System in Patients With Type 1 Diabetes

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Drug: Extended bolus of insulin then standard bolus of insulin
* Drug: Standard bolus of insulin then extended bolus of insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Age between 13 and 18 years old, A1C > 6% at screening Diagnosed with type 1 diabetes for at least one year Total daily dose (TDD) of insulin ≥ 0.3 units/kg/day Currently using the Control IQ closed-loop system Willing to abide by meal recommendations and study procedures Willing and able to sign the Informed Consent Form (ICF) and/or has a parent or guardian willing and able to sign the ICF Use an Android or Apple smartphone Willingness not to start any new non-insulin glucose-lowering agent during the course of the trial Participant and parent(s)/guardian(s) willingness to participate in all training sessions as directed by study staff Parent/guardian proficient in reading and writing English Live in the United States, with no plans to move outside the United States during the study period Exclusion Criteria A1C >10% One or more episodes of severe hypoglycemia or DKA requiring ER visit or hospitalization within the past three months Used non-insulin anti-diabetic medication within the last 30 days other than metformin Known history of gastroparesis, seizure disorder, adrenal insufficiency, or ongoing renal or hepatic disease Pregnancy or lactation Untreated or unstable hypothyroidism Currently undergoing cancer treatment or systemic treatment with steroids Untreated or inadequately treated mental illness Current alcohol abuse Current illness that would interfere with participation in the study Delayed gastric emptying or any concurrent conditions that can be associated with delayed gastric emptying or altered digestion; and the use of any medication that affects gastric emptying Celiac Disease

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Participants will be randomly assigned (1:1) in blocks of two to the order in which they receive the two premeal insulin boluses: extended followed by standard bolus or a standard followed by extended bolus.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High Fat High Protein (HFHP) Meal- extended then standard insulin bolus arm<br>Subjects will receive extended meal bolus for breakfast on the first day and standard meal bolus on the second day of the study. | Drug: Extended bolus of insulin then standard bolus of insulin<br>* For a standardized HFHP breakfast, participants will receive an extended meal bolus of insulin on the first morning and a standard meal bolus of insulin on the second morning of the study.<br>|
| Experimental: High Fat High Protein (HFHP) Meal- standard then extended insulin bolus arm<br>Subjects will receive standard meal bolus for breakfast on the first day and extended meal bolus on the second day. | Drug: Standard bolus of insulin then extended bolus of insulin<br>* For a standardized HFHP breakfast, participants will receive a standard bolus of insulin on the first morning and an extended bolus of insulin on the second morning of the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose Area Under Curve [AUC] | Area under the curve between glucose trace and starting glucose (mg/dL* hour) | Baseline and 5 hours post-bolus | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of time between 70-180 mg/dL | Percentage of time spent between 70-180 mg/dl based on Continuous Glucose Monitor (CGM) values | Baseline and 5 hours post-bolus | 
| Percentage of time in hypoglycemic range (defined as < 70 mg/dL) | Percentage of time spent with blood sugar less than 70 mg/dL based on Continuous Glucose Monitor (CGM) values | Baseline and 5 hours post-bolus | 
| Average glucose | Average glucose value based on Continuous Glucose Monitor (CGM) values | Baseline and 5 hours post-bolus | 
| Percentage of time in hyperglycemic range (defined as ≥180 mg/dL); | Percentage of time spent with blood sugar higher than 180 mg/dL based on Continuous Glucose Monitor (CGM) values | Baseline and 5 hours post-bolus | 
| Insulin dosage | Total insulin received during 5 hrs ( manual bolus as well as automated) | Baseline and 5 hours post-bolus | 
| Time to target | Time spent till blood glucose returns to range | Baseline and 5 hours post-bolus | 
| Time to baseline | Time spent till blood glucose returns to baseline | Baseline and 5 hours post-bolus | 
| Time to peak glucose | Time spent till blood glucose reaches the maximum value after meal | Baseline and 5 hours post-bolus | 
| Change in glucose | The difference between baseline to max glucose value | Baseline and 5 hours post-bolus | 
| Peak glucose concentration | Max blood glucose | Baseline and 5 hours post-bolus | 
| Percentage of time between 70-140 mg/dL | Percent of glucose readings from CGM system between 70-140 mg/dL per unit of time | Baseline and 5 hours post-bolus |