The International Diabetes Closed Loop (iDCL) Trial: Protocol 4

Study Overview
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Brief Summary
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The investigators aim to compare the efficacy and safety of an AID system using an adaptive MPC algorithm versus SAP (which may or may not include PLGS; to be referred to as SAP) in people with type 1 diabetes.

Detailed Description
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A randomized crossover trial will compare the efficacy and safety of an automated insulin delivery (AID) study system using an adaptive Model Predictive Control (MPC) algorithm versus SAP (which may or may not include PLGS; to be referred to as SAP) therapy in people with type 1 diabetes for 13 weeks in each arm of the study. A Pilot Phase using the study system for 10-14 days will be conducted prior to the crossover trial.

Official Title
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The International Diabetes Closed Loop (iDCL) Trial: A Randomized Crossover Comparison of Adaptive Model Predictive Control (MPC) Artificial Pancreas Versus Sensor Augmented Pump (SAP)/Predictive Low Glucose Suspend (PLGS) in the Outpatient Setting in Type 1 Diabetes (DCLP4)

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Device: interoperable Artificial Pancreas System (iAPS)
* Other: Sensor-Augmented Pump (SAP)/Predictive Low Glucose Suspend (PLGS)


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 (which may include use of automated features) Familiarity and use of a carbohydrate ratio for meal boluses Age ≥18.0 years old 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. If using a personal CGM, willingness to use a Dexcom G6 CGM and discontinue personal CGM use during the study Willing not to begin use of, or not to continue use of if currently using, a personal AID (closed loop control) system during the study; note if the system offers an open-loop mode or can be switched to a PLGS mode that is compatible with the Dexcom G6, the system may be used during the study in these modes only 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, and not to use Afrezza during the trial Investigator believes that the participant can successfully and safely operate all study devices and is capable of adhering to the protocol Exclusion Criteria: Use of Afrezza or any non-insulin glucose-lowering agent other than metformin (including GLP-1 agonists, DPP-4 inhibitors, SGLT-2 inhibitors, sulfonylureas) unless participant is willing to discontinue during the trial. Two or more episodes of DKA requiring an emergency room visit or hospitalization in the past 6 months Two or more episodes of severe hypoglycemia with seizure or loss of consciousness in the last 6 months Hemophilia or any other bleeding disorder A medical or other condition that in the opinion of the investigator could create a safety concern for the participant or put the study at risk. History of frequent severe hypoglycemia or history of frequent severe hyperglycemia and/or ketosis, without emergency room visit or hospitalization, due to poor diabetes self-management may be disqualifying per investigator judgment Participation in another pharmaceutical or device trial at the time of enrollment or during the study

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: Artificial Pancreas<br>Subjects will be provided the Interoperable Artificial Pancreas System (iAPS) which includes the iAPS phone platform, a study insulin pump, study continuous glucose monitor (CGM), and a study glucometer. This iAPS is designed to help control blood sugar in people living with type 1 diabetes. | Device: interoperable Artificial Pancreas System (iAPS)<br>* Use of the iAPS at home for 13 weeks, with weekly adaptation of insulin delivery settings occurring automatically in the iAPS.<br>|
| Active Comparator: Sensor Augmented Pump/Predictive Low Glucose Suspend<br>Subjects will continue use of home insulin pump with a study continuous glucose monitor (CGM) and study glucometer. Subject may use home pump in PLGS mode if this is supported and compatible with the study sensor. | Other: Sensor-Augmented Pump (SAP)/Predictive Low Glucose Suspend (PLGS)<br>* Use of personal pump with study CGM & glucometer at home for 13 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent CGM Time in Range 70-180 mg/dL | This results shown is mean percent time in range 70-180 mg/dL. | 13 weeks | 
| Non-inferiority for CGM Time <54 mg/dL | Superiority for time in range 70-180 mg/dL and non-inferiority for time <54 mg/dL measured with CGM will be considered primary endpoints, analyzed using a hierarchical gatekeeping testing procedure | 13 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CGM Mean Glucose | CGM-measured mean glucose (mg/dL) | 13 weeks | 
| CGM Time > 180 | CGM time > 180 mg/dL | 13 weeks | 
| CGM Time > 250 | CGM time > 250 mg/dL | 13 weeks | 
| CGM Time < 70 | CGM time < 70 mg/dL | 13 weeks | 
| CGM Time < 54 (Superiority) | CGM time < 54 mg/dL (Superiority) | 13 weeks | 
| Coefficient of Variation | CGM measured glucose variability measured with the coefficient of variation (CV) | 13 weeks | 
| CGM Time in Range 70-140 mg/dL | CGM-measured % in range 70-140 mg/dL | 13 weeks | 
| Standard Deviation | CGM measured glucose variability measured with the standard deviation (SD) | 13 weeks | 
| CGM Time < 60 | CGM time < 60 mg/dL | 13 weeks | 
| LBGI | Low blood glucose index (LBGI) by CGM with higher index indicating higher risk of hypoglycemia. LBGI ≤ 1.1 is associated with minimal risk of hypoglycemia, 1.1 < LBGI ≤ 2.5 is associated with a low risk of hypoglycemia, 2.5 < LBGI ≤ 5.0 is associated with a moderate risk of hypoglycemia, and LBGI > 5.0 is associated with high risk of hypoglycemia. | 13 weeks | 
| CGM Time > 300 | CGM time > 300 mg/dL | 13 weeks | 
| HBGI | High Blood Glucose Index (HBGI) is a measure of Hyperglycemic Risk based on frequency and severity of hyperglycemic events. HBGI < 4.5 is associated with lower risk of hyperglycemia, 4.5 < HBGI < 9 is associated with a moderate risk of hyperglycemia and HBGI > 9 is associated with high risk of hyperglycemia | 13 weeks | 
| HbA1c at 13 Weeks | Hemiglobin A1c measured after completing each study arm | 13 weeks | 
| Number of Participants With HbA1c <7.0% at 13 Weeks | Number of participants HbA1c <7.0% after completing each study arm | 13 weeks | 
| Number of Participants With HbA1c <7.5% at 13 Weeks | Number of participants HbA1c <7.5% after completing each study arm | 3 months | 
| Diabetes Distress Scale at 13 Weeks - Total Score | Diabetes Distress Scale for adults has 28 items rated on a 6 point Likert scale that ranges from 1 (not a problem) to 6 (a very serious problem). The total score is the mean of the sum of responses and ranges from 1 to 6 where a higher score indicates greater degrees of diabetes distress. | 13 weeks | 
| Glucose Monitoring Satisfaction Survey (Total Scale) | The GMSS for Type 1 Diabetes contains four subscales as well as a total scale. For this measure, total scale is reported. To calculate the total scale (higher scores indicate greater satisfaction): Mean of all items 1-15 (reverse code items: 2-7, 9, 11-13, and 15) which are all scored on a 5 point scale (1-5) (Minimum Total Scale Score is 1, Maximum Total Scale Score is 5) | 13 weeks | 
| Hypoglycemia Confidence Scale | Hypoglycemia Confidence Scale has 20 items which are rated on a 4-point Likert Scale ranging from 1 (not confident at all) to 4 (very confident) with higher scores indicating higher confidence in dealing with hypoglycemia. A single score is computed by calculating the mean of the sum of all items and ranges from 1 to 4. | 13 weeks | 
| INSPIRE Survey Scores - Following Study System Period Only | The INSPIRE questionnaire assesses user expectations and experiences with Insulin Delivery Systems: Perceptions, Ideas, Reflections, Expectations (INSPIRE). Survey total scores are computed by calculating the mean of the sum of all item ratings then multiplying the mean by 25 to scale the score to a range from 0 to 100. Higher scores indicate a more positive perception of insulin delivery systems. Items are rated on a 5 point Likert scale ranging from 0 (strongly disagree) to 4 (strongly agree). The Adult survey has 22 items, the Teens/Adolescents survey has 17 items and the Parent survey has 21 items. | 13 weeks | 
| SUS Survey Scores - Following Study System Period | System Usability Scores (SUS)-composite score from 0 to 100 with higher scores indicate better perceived usability | 13 weeks | 
| Total Daily Insulin | Total Daily Insulin (units) | 13 weeks | 
| Basal: Bolus Insulin Ratio | Basal: bolus insulin ratio | 13 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Artificial Pancreas, Automated Insulin Delivery, Closed Loop Control, Continuous Glucose Monitor (CGM), interoperable Artificial Pancreas System (iAPS)