A Study of t:Slim X2 With Control-IQ Technology

Study Overview
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Brief Summary
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The purpose of this study is to learn whether an investigational automated insulin delivery system (study system) for children with type 1 diabetes can safely improve blood glucose (sometimes called blood sugar) control. The system uses continuous glucose monitoring (CGM), an insulin pump, and a software algorithm to automatically give insulin and control blood glucose. This is called a closed-loop control system.

Detailed Description
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After consent is signed, eligibility will be assessed. Eligible participants not currently using an insulin pump and Dexcom CGM with minimum data requirements will initiate a run-in phase of 2-4 weeks that will be customized based on whether the participant is already a pump or CGM user. Participants who skip or successfully complete the run-in will be randomly assigned 3:1 to the use of closed-loop control (CLC group) using t:slim X2 with Control-IQ Technology vs. Control Group for 16 weeks. The Control Group will be offered to transition to use CLC and the experimental arm will extend their use of CLC for 12 weeks.

Official Title
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The International Diabetes Closed Loop (iDCL) Trial: Clinical Acceptance of the Artificial Pancreas in Pediatrics: A Study of t:Slim X2 With Control-IQ Technology

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Device: t:slim X2 with Control-IQ Technology & Dexcom G6 CGM
* Device: Control Group


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 6 months Familiarity and use of a carbohydrate ratio for meal boluses. Age ≥ 6 and ≤ 13 years old Weight ≥25 kg and ≤140 kg 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. Living with one or more parent/legal guardian knowledgeable about emergency procedures for severe hypoglycemia and able to contact emergency services and study staff. Willingness to suspend use of any personal closed loop system that they use at home for the duration of the clinical trial once the study CGM is in use Investigator has confidence that the participant can successfully operate all study devices and is capable of adhering to the protocol 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 for participants using to t:slim X2. This includes: Participants randomized to Control IQ Participants on the SAP group on MDI treatment that will be provided a Tandem pump to switch to CSII Participates that are already in Continuous Subcutaneous Insulin Infusion (CSII) randomized to SAP during the extension phase when transition to Control IQ Total daily insulin dose (TDD) at least 10 U/day 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. Exclusion Criteria: Concurrent use of any non-insulin glucose-lowering agent other than metformin (including glucagon-like peptide [GLP-1] agonists, Symlin, dipeptidyl peptidase 4 [DPP-4] inhibitors, sodium-glucose cotransporter-2 (SGLT2) inhibitors, sulfonylureas). Hemophilia or any other bleeding disorder A condition, which in the opinion of the investigator or designee, would put the participant or study at risk (specified on the study procedure manual) Participation in another pharmaceutical or device trial at the time of enrollment or during the study Employed by, or having immediate family members employed by Tandem Diabetes Care, Inc., or 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: 6 Years
Maximum Age: 13 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Closed Loop Control (CLC)<br>Eligible participants not currently using an insulin pump and Dexcom G4, G5 or Dexcom G6 CGM with minimum data requirements will initiate a run-in phase of 2 to 4 weeks that will be customized based on whether the participant is already a pump or CGM user. Participants who skip or successfully complete the run-in will be randomly assigned 3:1 to the use of closed-loop control (CLC group) system using Tandem Control-IQ Technology & Dexcom G6 CGM vs Control Group for 16 weeks. Participants randomized to the closed loop control (CLC) arm will use the t:slim X2 with Control-IQ Technology & Dexcom G6 CGM for 16 weeks. All participants will be provided the option of continue using the t:slim X2 with Control-IQ system in a 12 week Extension Phase. | Device: t:slim X2 with Control-IQ Technology & Dexcom G6 CGM<br>* Eligible participants will be use the t:slim X2 with Control-IQ Technology & Dexcom G6 CGM technology for 16 weeks during the main study. All participants will be provided the option of continue using the t:slim X2 with Control-IQ system in a 12 week Extension Phase. This arm to be uset:slim X2 with Control-IQ Technology & Dexcom G6 CGM<br>* Other names: Experimental;|
| Active Comparator: Control Group<br>Eligible participants not currently using an insulin pump and Dexcom G4, G5 or Dexcom G6 CGM with minimum data requirements will initiate a run-in phase of 2 to 4 weeks that will be customized based on whether the participant is already a pump or CGM user. Participants who skip or successfully complete the run-in will be randomly assigned 3:1 to the use of closed-loop control (CLC group) system using Tandem t:slim X2 with Control-IQ Technology vs Control Group for 16 weeks. All participants will be provided the option of using t:slim X2 with Control-IQ system in a 12 week Extension Phase. | Device: Control Group<br>* Eligible participants will be use the study Dexcom G6 CGM for 16 weeks during the main study. All participants will be provided the option of using the t:slim X2 with Control-IQ system in a 12 week Extension Phase.<br>* Other names: Sensor-Augmented Pump (SAP);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Continuous Glucose Monitor (CGM)-Measured Percent Time in Range 70-180mg/dL Over 16 Week Trial Period | The primary outcome for the first phase is percent of time participants spent in blood sugar target range 70-180 mg/dL as measured by CGM in Closed Loop Control (CLC) group vs. Control Group. Larger percentages of time spent in this range is considered to be a desirable outcome. | From randomization to data collection completion at the end of 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CGM-Measured Percent of Time Above 180 mg/dL Over 16 Week Trial Period | Continuous Blood Glucose Monitor (CGM) values are generated every 5 minutes over the course of the study. Smaller percentages of CGM-measured time above 180 mg/dL is considered a positive outcome. | From randomization to data collection completion at the end of 16 weeks | 
| CGM-Measured Mean Glucose Over 16 Week Trial Period | Continuous Blood Glucose Monitor (CGM) values are generated every 5 minutes over the course of the study. CGM metrics were calculated by pooling all CGM readings in the 16-week period starting from the randomization visit up through the 16 week visit. If a participant dropped out before completing the 16-week visit, all available data through the last visit date was included for calculating CGM metrics. Minimum 168 hours of CGM data was required to calculate CGM metrics. Lower mean glucose numbers as measured by CGM in mg/dL is considered a positive outcome. | From randomization to data collection completion at the end of 16 weeks | 
| Glycated Hemoglobin A1C (HbA1c) Percent at End Of 16 Week Trial Period | Glycated Hemoglobin A1C (HbA1c) is a physiological marker of the percentage of red blood cells that have glycated (bonded with a sugar). HbA1c is used to measure changes in average blood sugar over the past three months. 5-6% is normal, 7% and above is correlated with negative long-term health outcomes. | At data collection completion at the end of 16 weeks | 
| CGM-measured Percent of Time Below 70 mg/dL Over 16 Week Trial Period | Continuous Blood Glucose Monitor (CGM) values are generated every 5 minutes over the course of the study. CGM measured blood sugar values below 70 mg/dL are considered to be somewhat dangerous due to the possibility of unconsciousness and death at low blood sugar values. Thus, less time spent below 70mg/dL is considered a positive outcome. | From randomization to data collection completion at the end of 16 weeks | 
| CGM-measured Median and Interquartile Range of Percent of Time Below 54 mg/dL Over 16 Week Trial Period | GM measured blood sugar values below 54 mg/dL have the potential to lead to unconsciousness or death. Thus, less time below 54 mg/dL is considered a better outcome. | From randomization to data collection completion at the end of 16 weeks | 
| CGM-measured Percent of Time Above 250 mg/dL Over 16 Week Trial Period | CGM measured blood sugar values above 250 mg/dL are considered to be undesirable. Thus, less time spent above 250mg/dL is considered a positive outcome. | From randomization to data collection completion at the end of 16 weeks | 
| Continuous Glucose Monitor (CGM)-Measured Glucose Variability Measured With the Coefficient of Variation (CV) Over 16 Week Trial Period | Continuous Blood Glucose Monitor (CGM) values are generated every 5 minutes over the course of the study. CGM metrics were calculated by pooling all CGM readings in the 16-week trial period starting from randomization visit to week 16 visit. If a participant drops out before completing the 16-week visit, all available data through the last visit date will be included for calculating CGM metrics. Minimum 168 hours of CGM data were required to calculate CGM metrics. Coefficient of Variability (CV) is the ratio of the standard deviation to the mean of the blood sugar values of each participant as measured by CGM. The reported value is the mean and standard deviation of the participant outcomes multiplied by 100. This shows the extent of the mean variability of the blood sugar values in the population. Higher CV values (up to 100) indicate greater dispersion of CGM values, which would indicate more blood sugar variability, which is considered a negative outcome. Minimum value is 0. | From randomization to data collection completion at the end of 16 weeks | 
| CGM-measured Percent of Time Above 180 mg/dL Over 12 Week Trial Extension Period | Continuous Blood Glucose Monitor (CGM) values are generated every 5 minutes over the course of the study. CGM metrics were calculated by pooling all CGM readings in the 12-week period starting from the 16 week visit at the end of the main study up through the 28th week visit. If a participant drops out before completing the 28-week visit, all available data through the last visit date will be included for calculating CGM metrics. Minimum 168 hours of CGM data will be required to calculate CGM metrics. Smaller percentages of CGM-measured percentages of time above 180 mg/dL is considered a positive outcome. | From completion of the first 16 weeks of the main study to data collection completion at the end of 12 weeks | 
| CGM-measured Mean Glucose Over 12 Week Trial Extension Period | Continuous Blood Glucose Monitor (CGM) values are generated every 5 minutes over the course of the study. Lower mean glucose numbers as measured by CGM in mg/dL is considered a positive outcome. | From completion of the first 16 weeks of the main study to data collection completion at the end of 12 weeks | 
| Glycated Hemoglobin Percent (HbA1c) at Conclusion of 12 Week Trial Extension Period | Hemoglobin A1C (HbA1c) is a physiological marker of the percentage of red blood cells that have glycated (bonded with a sugar). HbA1c is used to measure changes in average blood sugar over the past three months. 5-6% is normal, 7% and above is correlated with negative long-term health outcomes. | At completion of the extension study, end of week 28 | 
| CGM-measured Percent of Time Below 70 mg/dL Over 12 Week Trial Extension Period | Continuous Blood Glucose Monitor (CGM) values are generated every 5 minutes over the course of the study. CGM measured blood sugar values below 70 mg/dL are considered to be undesirable. Thus, less time spent below 70mg/dL is considered a positive outcome. | From completion of the first 16 weeks of the main study to data collection completion at the end of 12 weeks | 
| CGM-measured Percent of Time Below 54 mg/dL Over 12 Week Trial Extension Period | Continuous Blood Glucose Monitor (CGM) values are generated every 5 minutes over the course of the study. CGM measured blood sugar values below 54 mg/dL have the potential to lead to unconsciousness or death. Thus, time below 54 mg/dL suggests that the person may have been close to danger. | From completion of the first 16 weeks of the main study to data collection completion at the end of 12 weeks | 
| CGM-measured Percent of Time Above 250 mg/dL Over 12 Week Trial Extension Period | Continuous Blood Glucose Monitor (CGM) values are generated every 5 minutes over the course of the study. CGM measured blood sugar values above 250 mg/dL are considered to be undesireable. Thus, less time spent above 250mg/dL is considered a positive outcome. | From completion of the first 16 weeks of the main study to data collection completion at the end of 12 weeks | 
| Continuous Glucose Monitor (CGM)-Measured Glucose Variability Percentage Measured With the Coefficient of Variation (CV) Over 12 Week Trial Extension Period | Continuous Blood Glucose Monitor (CGM) values are generated every 5 minutes over the course of the study. CGM metrics were calculated by pooling all CGM readings in the 12-week trial extension period starting from 16 week visit to week 28 visit. If a participant drops out before completing the 32-week visit, all available data through the last visit date will be included for calculating CGM metrics. Minimum 168 hours of CGM data were required to calculate CGM metrics. Coefficient of Variability (CV) is the ratio of the standard deviation to the mean of the blood sugar values of each participant as measured by CGM. The reported value is the mean and standard deviation of the participant outcomes multiplied by 100. This shows the extent of the mean variability of the blood sugar values in the study group. Higher CV values (up to 100) indicate greater dispersion of CGM values, which would indicate more blood sugar variability, which is considered a negative outcome. Minimum value is 0. | From completion of the first 16 weeks of the main study to data collection completion at the end of 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Artificial Pancreas (AP), Control-IQ System, Insulin Pump, Closed Loop Control (CLC), Continuous Glucose Monitor (CGM), Multiple Daily Injections (MDI), Sensor Augmented Pump (SAP)