Diabetes Closed-Loop Project 6 (DCLP6): Fully Automated Closed-Loop Control in Type 1 Diabetes Using Meal Anticipation

Study Overview
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Brief Summary
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The purpose of this study is to test the meal anticipation module on a closed loop algorithm, assessing efficacy and safety.

Detailed Description
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This is a pilot study to assess glycemic responses to three different approaches to insulin dosing for carbohydrate ingestion, with different approaches to a closed-loop system in random order; without the meal anticipation module and without carbohydrate announcement (FCL) with the meal anticipation module and without carbohydrate announcement (FCL+) without the meal anticipation module and with carbohydrate announcement (HCL), This study will target completion of up to 36 adults in a randomized cross-over trial, comparing blood glucose time in range 70-180 mg/dL following meals with and without the meal anticipation module in use (FCL+ vs FCL), and comparing to a system with carb announcement instead of a meal anticipation module (HCL). The study will also assess safety when dinner is consumed later than usual and when a lunch is consumed without having been entrained in the meal anticipation module. Each participant will complete each of the 3 modules in random order.

Official Title
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Diabetes Closed-Loop Project 6 (DCLP6): Fully Automated Closed-Loop Control in Type 1 Diabetes Using Meal Anticipation

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Device: Fully Closed Loop (FCL)
* Device: Fully Closed Loop with meal anticipation module (FCL+)
* Device: Hybrid Closed Loop (HCL)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18.0 and ≤70 years old at time of consent Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least one year Currently using insulin for at least six months Currently using insulin pump for at least three months 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 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 childbearing 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 suspend use of any personal CGM for the duration of the clinical trial once the study CGM is in use Willingness to use the University of Virginia (UVa) closed-loop system throughout study admission Willingness to use the insulin supplied by the study for the hotel stay, if not already using that preparation. Study insulin will be lispro (Humalog) or aspart (Novolog) Willingness not to start any new 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 1g/kg of carbohydrate per day during the hotel admission Willingness to reschedule if placed on oral steroids An understanding and willingness to follow the protocol and signed informed consent Willingness to commit to self-quarantine for at least 5 days before COVID-19 testing (If participant has received a full course of COVID-19 vaccine and data emerge suggesting significantly reduced transmissibility among those receiving that vaccine, this self-quarantine requirement can be waived.) Exclusion Criteria: History of diabetic ketoacidosis (DKA) in the 12 months prior to enrollment Severe hypoglycemia resulting in seizure or loss of consciousness in the 12 months prior to enrollment Pregnancy or intent to become pregnant during the trial Currently being treated for a seizure disorder Planned surgery during study duration Treatment with any non-insulin glucose-lowering agent (including 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 automated insulin delivery mechanism that is not downloadable by the subject or study team Known contact with a COVID-19 positive individual within 14 days of the hotel/rental house studies.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: FCL (Fully Closed Loop)<br>Closed-loop control without meal anticipation module without meal bolus | Device: Fully Closed Loop (FCL)<br>* Closed loop without a meal anticipation module without announced carbohydrate<br>|
| Experimental: FCL+ (Fully Closed Loop with meal anticipation)<br>Closed-loop control with meal anticipation module without meal bolus | Device: Fully Closed Loop with meal anticipation module (FCL+)<br>* Closed loop with a meal anticipation module and without announced carbohydrate<br>|
| Experimental: HCL (Hybrid Closed Loop)<br>Closed-loop control without meal anticipation module with meal bolus | Device: Hybrid Closed Loop (HCL)<br>* Closed loop without a meal anticipation module with announced carbohydrate<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time in Range (TIR) 70-180 mg/dL From Breakfast Time + 5 Hours | Frequency of CGM values falling between 70 mg/dL and 180mg/dL (included) in the 5 hours following breakfast. Higher TIR is a positive outcome. | The 5 hour period following breakfast during the study admission | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time in Range (TIR) 70-180 mg/dL Overall | Frequency of CGM values falling between 70 mg/dL and 180mg/dL (included) during the 24hr study admission. Higher TIR is a positive outcome. | The 24 hour study admission from 4pm to 4pm | 
| Time in Range (TIR) 70-180 mg/dL From Dinner Time + 5 Hours | Frequency of CGM values falling between 70 mg/dL and 180mg/dL (included) in the 5 hours following dinner. Higher TIR is a positive outcome. | The 5 hour period following dinner during the study admission | 
| Time in Range (TIR) 70-180 mg/dL From Lunch Time + 5 Hours | Frequency of CGM values falling between 70 mg/dL and 180mg/dL (included) in the 5 hours following lunch. Higher TIR is a positive outcome. | The 5 hour period following lunch during the study admission | 
| Time Below Range (TBR) From Breakfast Time + 5 Hours | Frequency of CGM values falling below 70 mg/dL (excluded) in the 5 hours following breakfast. | The 5 hour period following breakfast during the study admission | 
| Time Below Range (TBR) Overall | Frequency of CGM values falling below 70 mg/dL (excluded) during the 24hr study admission. | The 24 hour study admission from 4pm to 4pm | 
| Time Below Range (TBR) From Dinner Time + 5 Hours | Frequency of CGM values falling below 70 mg/dL (excluded) in the 5 hours following dinner. | The 5 hour period following dinner during the study admission | 
| Time Below Range (TBR) From Lunch Time + 5 Hours | Frequency of CGM values falling below 70 mg/dL (excluded) in the 5 hours following lunch. | The 5 hour period following lunch during the study admission | 
| Time Above Range (TAR) From Breakfast Time + 5 Hours | Frequency of CGM values falling above 180 mg/dL (excluded) in the 5 hours following breakfast. | The 5 hour period following breakfast during the study admission | 
| Time Above Range (TAR) Overall | Frequency of CGM values falling above 180 mg/dL (excluded) during the 24hr study admission. | The 24 hour study admission from 4pm to 4pm | 
| Time Above Range (TAR) From Dinner Time + 5 Hours | Frequency of CGM values falling above 180 mg/dL (excluded) in the 5 hours following dinner. | The 5 hour period following dinner during the study admission | 
| Time Above Range (TAR) From Lunch Time + 5 Hours | Frequency of CGM values falling above 180 mg/dL (excluded) in the 5 hours following lunch. | The 5 hour period following lunch during the study admission | 
| Time in Significant Hyperglycemia From Breakfast Time + 5 Hours | Frequency of CGM values falling above 250 mg/dL (excluded) in the 5 hours following breakfast. | The 5 hour period following breakfast during the study admission | 
| Time in Significant Hyperglycemia Overall | Frequency of CGM values falling above 250 mg/dL (excluded) during the 24hr study admission. | The 24 hour study admission from 4pm to 4pm | 
| Time in Significant Hyperglycemia From Dinner Time + 5 Hours | Frequency of CGM values falling above 250 mg/dL (excluded) in the 5 hours following dinner. | The 5 hour period following dinner during the study admission | 
| Time in Significant Hyperglycemia From Lunch Time + 5 Hours | Frequency of CGM values falling above 250 mg/dL (excluded) in the 5 hours following lunch. | The 5 hour period following lunch during the study admission | 
| Time in Significant Hypoglycemia From Breakfast Time +5 Hours | Frequency of CGM values falling below 54 mg/dL (excluded) in the 5 hours following breakfast. | The 5 hour period following breakfast during the study admission | 
| Time in Significant Hypoglycemia Overall | Frequency of CGM values falling below 54 mg/dL (excluded) during the 24hr study admission. | The 24 hour study admission from 4pm to 4pm | 
| Time in Significant Hypoglycemia Dinner Time + 5 Hours | Frequency of CGM values falling below 54 mg/dL (excluded) in the 5 hours following dinner. | The 5 hour period following dinner during the study admission | 
| Time in Significant Hypoglycemia Lunch Time + 5 Hours | Frequency of CGM values falling below 54 mg/dL (excluded) in the 5 hours following lunch | The 5 hour period following lunch during the study admission | 
| Number of Hypoglycemia Events From Breakfast Time + 5 Hours | Number of hypoglycemia events in the 5 hours following breakfast. A hypoglycemia event is defined as at least two consecutive CGM values <70mg/dL or a hypoglycemia treatment (two events separated by less than 30 minutes are counted as one). Metrics are number of hypoglycemia events per participant. | The 5 hour period following breakfast during the study admission | 
| Number of Hypoglycemia Events Overall | Number of hypoglycemia events during the 24hr study admission. A hypoglycemia event is defined as at least two consecutive CGM values <70mg/dL or a hypoglycemia treatment (two events separated by less than 30 minutes are counted as one). Values reported as the number of hypoglycemia events per participant. | The 24 hour study admission from 4pm to 4pm | 
| Number of Hypoglycemia Events Dinner Time + 5 Hours | Number of hypoglycemia events in the 5 hours following dinner. A hypoglycemia event is defined as at least two consecutive CGM values <70mg/dL or a hypoglycemia treatment (two events separated by less than 30 minutes are counted as one). Values reported as the number of hypoglycemia events per participant. | The 5 hour period following dinner during the study admission | 
| Number of Hypoglycemia Events Lunch Time + 5 Hours | Number of hypoglycemia events in the 5 hours following lunch. A hypoglycemia event is defined as at least two consecutive CGM values <70mg/dL or a hypoglycemia treatment (two events separated by less than 30 minutes are counted as one). | The 5 hour period following lunch during the study admission | 
| Units of Insulin Injected Between 2 Hours Before and 5 Hours After Breakfast | Sum of all system provided insulin for breakfast (as planned) post-prandial excursion, including anticipation | The 7 hour period including the two hours before and the 5 hours after breakfast | 
| Units of Insulin Injected (Units/kg) Overall | Calculation of all system-provided insulin (units/kg) injected during the 24hr study admission. | The 24 hour study admission from 4pm to 4pm | 
| Units of Insulin Injected Between 2 Hours Before and 5 Hours After Dinner | Sum of all system provided insulin for dinner (late) post-prandial excursion, including anticipation | The 7 hour period including the 2 hours before and 5 hours after dinner | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 1 Diabetes (T1D), Continuous Glucose Monitor (CGM), Insulin Pump, Fully Automated Closed Loop (FCL), Hybrid Closed Loop (HCL)