The International Diabetes Closed Loop (iDCL) Trial: Clinical Acceptance of the Artificial Pancreas (DCLP3 Extension)

Study Overview
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Brief Summary
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This is a 3-month extension study (DCLP3 Extension) following a primary trial (DCLP3 or NCT03563313) to assess efficacy and safety of a closed loop system (t:slim X2 with Control-IQ Technology) in a large randomized controlled trial. Upon completion of the NIH 3-month extension study, subjects will be invited to participate in a continued use phase with Control-IQ Technology, funded by Tandem Diabetes Care, until the equipment has received FDA approval for commercial use.

Detailed Description
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Participants in the 6 month primary trial (DCLP3) will be invited to continue in this 3-month extension study (DCLP3 Extension) following completion of the primary trial. The closed-loop control (CLC) Intervention Group participants from the primary trial will be randomly assigned to continue CLC or to switch to Predictive Low-Glucose Suspend (PLGS) therapy with t:slim X2 with Basal-IQ and Dexcom G6 for 3 months. The Sensor-Augmented Pump (SAP) Control Group participants from the primary trial will be assigned to CLC using t:slim X2 with Control-IQ Technology and Dexcom G6 (CGM) for 3 months. Upon completion of the extension study, subjects will be invited to participate in continued use of the Control-IQ Technology until the equipment has received FDA approval for commercial use. This extension phase has two separate objectives: Objective 1: Among participants who used CLC in the primary trial: the primary efficacy outcome for the randomized controlled trial (RCT) is time in target range 70-180 mg/dL measured by CGM in CLC group vs. PLGS group over 3 months. Safety outcomes also will be assessed Objective 2: Among participants who used SAP in the primary trial: the primary outcome is to obtain additional safety data. Efficacy also will be assessed as a pre-post within participant analysis Note: Primary Trial (DCLP3) is NCT03563313

Official Title
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An Extension 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: t:slim X2 with Basal-IQ & Dexcom G6 CGM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Successful completion of the original 6-month RCT within the prior 14 days 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 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. For participants <18 years old, living with one or more parent/legal guardian knowledgeable about emergency procedures for severe hypoglycemia and able to contact the participant in case of an emergency. Willingness to not use a personal CGM for the duration of the study Investigator has confidence that the participant can successfully operate all study devices and is capable of adhering to the protocol Willingness to use only lispro (Humalog) or aspart (Novolog), and to use no other insulin during the study. Willingness not to start any new non-insulin glucose-lowering agent during the course of the trial Exclusion Criteria Concurrent use of 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 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 Employed by, or having immediate family members employed by Tandem Diabetes Care, Inc., Dexcom, Inc., or TypeZero Technologies, LLC, 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: 14 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
Interventional Model Description: A randomized controlled trial of 3 months at home closed loop system vs. predictive-low glucose suspend.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Closed Loop Control (CLC)<br>Participants randomized to the closed loop control (CLC) arm will use the t:slim X2 with Control-IQ Technology & Dexcom G6 Continuous Glucose Monitor (CGM) for 3 months. Objective 1: This arm is participants who had 6 months of CLC in the primary trial (DCLP3 Pivotal Trial) Objective 2: This arm is participants who had 6 months of sensor-augmented pump (SAP) in the primary trial (DCLP3 Pivotal Trial) Objective 3: This arm is participants who had 3 months of CLC in the extension trial (DCLP3 Extension) will continue use of the Control-IQ Technology & Dexcom G6 CGM until the product is commercially available. | Device: t:slim X2 with Control-IQ Technology & Dexcom G6 CGM<br>* Participants will use the Tandem t:slim X2 insulin pump with Control-IQ Technology & Dexcom G6 CGM for 3 months.<br>|
| Active Comparator: Predictive-Low Glucose Suspend (PLGS)<br>Participants randomized to Predictive-Low Glucose Suspend (PLGS) will use the t:slim X2 with Basal-IQ & Dexcom G6 CGM for 3 months. Objective 1: This arm is participants who had 6 months of PLGS in the primary trial (DCLP3 Pivotal Trial) Objective 2: This arm is not applicable to objective 2 Objective 3: This arm is participants who had 3 months of PLGS in the extension trial (DCLP3 Extension) will continue use of the Control-IQ Technology & Dexcom G6 CGM until the product is commercially available. | Device: t:slim X2 with Basal-IQ & Dexcom G6 CGM<br>* Participants will use a Tandem t:slim X2 insulin pump with Basal-IQ and a study CGM (Dexcom G6) for 3 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time in Target Range | The primary exploratory outcome is time in target range 70-180 mg/dL measured by CGM comparing the randomized groups CLC vs PLGS. Results from SAP to CLC group is also included here without the primary intention of comparing to CLC vs PLGS groups. | 13 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CGM Time Above 180 | CGM-measured % above 180 mg/dL | 13 weeks | 
| CGM Mean Glucose | CGM-measured mean glucose | 13 weeks | 
| CGM Time Below 70 | CGM-measured % below 70 mg/dL | 13 weeks | 
| CGM Time Below 54 | CGM-measured % below 54 mg/dL | 13 weeks | 
| CGM Time in Range 70-140 mg/dL | CGM-measured % in range 70-140 mg/dL | 13 weeks | 
| Coefficient of Variation | CGM measured glucose variability measured with the coefficient of variation (CV) | 13 weeks | 
| Standard Deviation | CGM measured glucose variability measured with the standard deviation (SD) | 13 weeks | 
| CGM Time Below 60 | CGM-measured % below 60 mg/dL | 13 weeks | 
| LBGI | Low blood glucose index by CGM with higher index indicating higher risk of hypoglycemia. Values <1 suggest minimal risk. Index of risk of low blood glucose excursion based on a standard formula for non-linear transformation of the blood glucose scale (Kovatchev BP, Cox DJ, Gonder-Frederick LA, Young-Hyman D, Schlundt D, Clarke WL: Assessment of risk for severe hypoglycemia among adults with IDDM: validation of the low blood glucose index. Diabetes Care 21:1870-1875, 1998) | 13 weeks | 
| CGM Hypoglycemia Events | CGM-measured events of at least 15 consecutive minutes <70 mg/dL | 13 weeks | 
| CGM Time >250 | CGM-measured % >250 mg/dL | 13 weeks | 
| CGM Time >300 | CGM-measured % >300 mg/dL | 13 weeks | 
| HBGI | High blood glucose index by CGM with higher values indicating higher risk of hyperglycemia. Index of risk of high blood glucose excursion based on a standard formula for non-linear transformation of the blood glucose scale (Kovatchev BP, Cox DJ, Kumar A, Gonder-Frederick L, Clarke WL. Algorithmic evaluation of metabolic control and risk of severe hypoglycemia in type 1 and type 2 diabetes using self-monitoring blood glucose data. Diabetes Technol Ther 2003;5:817-828pmid:14633347) | 13 weeks | 
| HbA1c at 13 Weeks | HbA1c at 13 weeks. | 13 weeks | 
| HbA1c <7.0% at 13 Weeks | HbA1c <7.0% at 13 weeks. | 13 weeks | 
| HbA1c <7.5% at 13 Weeks | HbA1c <7.5% at 13 weeks. | 13 weeks | 
| HbA1c Change From Baseline to 13 Weeks >0.5% | HbA1c change from baseline to 13 weeks >0.5%. | 13 weeks | 
| HbA1c Change From Baseline to 13 Weeks >1.0% | HbA1c change from baseline to 13 weeks >1.0%. | 13 weeks | 
| HbA1c Relative Change From Baseline to 13 Weeks >10% | HbA1c relative change from baseline to 13 weeks >10%. | 13 weeks | 
| HbA1c Change From Baseline to 13 Weeks >1.0% or HbA1C <7.0% at 13 Weeks | HbA1c change from baseline to 13 weeks >1.0% or HbA1c <7.0% at 13 weeks. | 13 weeks | 
| HFS-II Adult | Fear of Hypoglycemia Survey (HFS-II) total score and 3 sub scales (5 point scale with never to almost always) For adults, teens and parents items on this survey are rated on a 5 point Likert scale from never (0) to almost always (4). The survey is scored by summing item responses. Fear of Hypoglycemia Survey (HFS-II) for adults has a total score that is summed from the two subscale scores (33 items) and ranges from 0 to 132 with higher scores indicating greater degrees of fear of hypoglycemia. | 13 weeks | 
| HFS-II Teen | Fear of Hypoglycemia Survey (HFS-II) total score and 3 sub scales (5 point scale with never to almost always) For adults, teens and parents items on this survey are rated on a 5 point Likert scale from never (0) to almost always (4). The survey is scored by summing item responses.The teen survey has a total of 25 items and the range of Total scores is 0 to 100. | 13 weeks | 
| HFS-II Parents | Fear of Hypoglycemia Survey (HFS-II) total score and 3 sub scales (5 point scale with never to almost always) For adults, teens and parents items on this survey are rated on a 5 point Likert scale from never (0) to almost always (4). The parent version of the survey has a total of 26 items with Total scores that range from 0 to 108. | 13 weeks | 
| Hyperglycemia Avoidance Scale | Hyperglycemia Avoidance Scale total score is the sum of 21 items rated on a 4 point Likert scale from 0 (never) to 4 (almost always) and ranges from 0 to 84 with a higher score indicating greater degrees of avoiding hyperglycemia. | 13 weeks | 
| Diabetes Distress Scale | 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 | 
| Hypoglycemia Confidence Scale | Hypoglycemia Confidence Scale has 9 items which are self-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 | 
| Clarke Hypoglycemia Awareness Scores | Clarke Hypoglycemia Awareness Scores (0-7 score with higher scores associated with impaired awareness) | 13 weeks | 
| INSPIRE Survey Scores- Adults | 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. | 13 weeks | 
| INSPIRE Survey Scores- Teens | 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 Teens/Adolescents survey has 17 items. | 13 weeks | 
| INSPIRE Survey Scores- Parents | 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 Parent survey has 21 items. | 13 weeks | 
| System Usability Scores (SUS) | System Usability Scores (SUS)-composite score from 0 to 100 with higher scores indicating better perceived usability | 13 weeks | 
| Technology Acceptance Questionnaire | Technology Acceptance Survey measures the user's perceptions regarding the burdens and the barriers associated with a technology with a higher score indicates increased technology acceptance. There total score uses 37 items with items are rated on a 5 point scale ranging from 1 (strongly disagree) to 5 (strongly agree) for total score range of 37-185. | 13 weeks | 
| Total Daily Insulin | Total Daily Insulin (units/kg) | 13 weeks | 
| Basal:Bolus Insulin Ratio | Basal:Bolus Insulin Ratio. | 13 weeks | 
| Weight | Weight (kg) | 13 weeks | 
| BMI | Body Mass Index (BMI) kg/m2 | 13 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Artificial Pancreas (AP), Type 1 Diabetes Mellitus, Insulin Pump, Continuous Glucose Monitor (CGM), Closed Loop Control (CLC), Sensor-Augmented Pump (SAP)