Model Predictive Control (MPC) Artificial Pancreas vs. Sensor Augmented Pump (SAP)/Predictive Low Glucose Suspend (PLGS) With Different Food Choices in the Outpatient Setting

Study Overview
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Brief Summary
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The objective of this randomized crossover clinical trial is to 1) assess the efficacy and safety of an automated insulin delivery (AID) system using a Model Predictive Control (MPC) algorithm versus sensor augmented pump therapy (SAP)/Predictive Low Glucose Suspend (PLGS) in people with type 1 diabetes, and 2) assess the impact of different meal macronutrient content on glucose control when using AID and SAP.

Detailed Description
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The goal of this study is to compare the efficacy and safety of an AID system using a MPC algorithm versus SAP/PLGS therapy with different food choices over a 4 week period. The AID system (iAPS) is comprised of an insulin pump, a Dexcom G6 continuous glucose monitoring sensor, and a smart phone that contains the algorithm and communicates with the other devices. In this study, during each two-week period, subjects will be given pre-weighed portions of different meals to eat (either regular semolina pasta or extra-long grain white rice) with detailed cooking instructions, and will eat these meals on 6 different occasions for dinner. They will bolus as they normally do for these meals. This will allow us to observe the postprandial meal response when using sensor-augmented pump (SAP) or iAPS, showing the importance of nutrition choices with modern technological treatments in T1D.

Official Title
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A Randomized Crossover Comparison of Model Predictive Control (MPC) Artificial Pancreas vs. Sensor Augmented Pump (SAP)/Predictive Low Glucose Suspend (PLGS) With Different Food Choices in the Outpatient Setting

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Device: iAPS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least one year and using insulin for at least 1 year. Using an insulin pump for at least 3 months at the time of screening. Insulin pump use includes use of automated features, to include predictive or threshold low-glucose suspend or hybrid closed-loop with without a Dexcom sensor. Familiarity and use of a carbohydrate ratio for meal boluses. Age ≥18.0 years old HbA1c < 10.5%, as performed by point of care or central laboratory testing. A1c will be assessed at the screening visit, or if already completed within 2 weeks of the screening visit, the prior lab value may be used in lieu of repeating this assessment. For females, not currently known to be pregnant. If female and sexually active, must agree to use a form of contraception to prevent pregnancy while a participant in the study. A negative serum or urine pregnancy test will be required for all females of child-bearing potential. Participants who become pregnant will be discontinued from the study. Also, participants who during the study develop and express the intention to become pregnant within the timespan of the study will be discontinued. Willingness to switch home pump to PLGS or full manual mode if using hybrid closed-loop with an FDA approved system. Have an emergency contact living at home with the subject who will be available to be contacted by the study staff overnight in the event of an emergency. Investigator has confidence that the participant can successfully operate all study devices and is capable of adhering to the protocol, to include having basic cooking equipment at home to prepare the study meals. 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. Willingness not to start any new non-insulin glucose-lowering agent during the course of the trial. Exclusion Criteria: Use of an unapproved closed-loop insulin delivery system within 2 weeks before screening or during the study is not allowed. Gastrointestinal disease such as celiac disease or multiple food allergies. Any form of gluten sensitivity or wheat allergy. Allergies to any form of nuts or ingredients present in the study meals (tomatoes etc). History of difficulty digesting food. Concurrent use of Afrezza or any non-insulin glucose-lowering agent other than metformin (including GLP-1 agonists, Symlin, DPP-4 inhibitors, SGLT-2 inhibitors, sulfonylureas). Hemophilia or any other bleeding disorder One or more episodes of hypoglycemia requiring an emergency room visit or hospitalization in the past 6 months. One or more episodes of hyperglycemia requiring an emergency room visit or hospitalization in the past 6 months. Self-reported or clinically documented hypoglycemia unawareness. A condition, which in the opinion of the investigator or designee, would put the participant or study at risk Participation in another pharmaceutical or device trial at the time of enrollment or during the study Having a direct supervisor at place of employment who is also directly involved in conducting the clinical trial (as a study investigator, coordinator, etc.); or having a first-degree relative who is directly involved in conducting the clinical trial

Ages Eligible for Study
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Minimum 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Automated Insulin Delivery<br>Participants will use the Automated Insulin Delivery (AID) iAPS system for 2 weeks in the outpatient setting. During AID use, subjects will consume 6 study meals (3 meals of each meal type in assigned random order, 1-2 portions per meal,) at dinner time over the 2-week period in a pre-assigned random order, and document on the study meal forms when they consume each numbered meal. | Device: iAPS<br>* The AID system (iAPS) is comprised of an insulin pump, a Dexcom G6 continuous glucose monitoring sensor, and a smart phone that contains the algorithm and communicates with the other devices.<br>|
| No Intervention: SAP/PLGS<br>Participants will use their home pump with a CGM sensor (sensor augmented pump) or in Predictive Low Glucose Suspend (PLGS) mode if their home pump supports this mode, for 2 weeks in the outpatient setting. During these 2 weeks, subjects will consume 6 study meals (3 meals of each meal type in assigned random order, 1-2 portions per meal,) at dinner time over the 2-week period in a pre-assigned random order, and document on the study meal forms when they consume each numbered meal. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time in target glucose range | Time in target glucose range 70-180 mg/dL measured by CGM to determine safety and efficacy of the integrated system | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postprandial glucose peak | Postprandial glucose peak rise (highest measurement in mg/dL) from baseline glucose (mg/dl) for the 5-hour period after the study meals, during both use of SAP/PLGS and when using the iAPS | 4 weeks | 
| Time to postprandial glucose peak | Time (minutes) to postprandial glucose (highest measurement in mg/dL) rise from baseline glucose (mg/dl) during the 5-hour period after the study meals, during both use of SAP/PLGS and when using the iAPS | 4 weeks | 
| Postprandial Area Under the Curve | Area Under the Curve Glucose (mg/dl x min) for the 5-hour period after the study meals, during both use of SAP/PLGS and when using the iAPS | 4 weeks | 
| Postprandial time for glucose to return to baseline | Time (minutes) for CGM glucose to return to baseline (starting value) after the study meals, during both use of SAP/PLGS and when using the iAPS | 4 weeks | 
| Glucose < 70 mg/dL | Percent time GGM glucose < 70 mg/dL | 4 weeks | 
| Glucose < 54 mg/dL | Percent time GGM glucose < 54 mg/dL | 4 weeks | 
| Glucose > 180 mg/dL | Percent time GGM glucose > 180 mg/dL | 4 weeks | 
| Glucose > 250 mg/dL | Percent time GGM glucose > 250 mg/dL | 4 weeks | 
| Serious adverse events (SAE) | The total number of serious adverse events during the clinical trial | 4 weeks | 
| Serious adverse device events (SADE) | The total number of serious adverse events related to the study device use during the clinical trial | 4 weeks | 
| Adverse device effects (ADE) | The total number of adverse device effects (ADE) during the clinical trial | 4 weeks | 
| Unanticipated adverse device effects (UADE) | The total number of unanticipated adverse device effects (UADE) during the clinical trial | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Artificial Pancreas, Hyperglycemia, Hypoglycemia, Nutrition