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

• ClinicalTrials.gov Identifier: NCT03563313
• Recruitment Status: Completed
• First Posted: June 20, 2018
• Results First Posted: April 28, 2020
• Last Update Posted: April 28, 2020
• Sponsor: University of Virginia
• Collaborators: Jaeb Center for Health Research; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Tandem Diabetes Care, Inc.; DexCom, Inc.; Roche Diagnostics
• Information provided by (Responsible Party): Sue Brown, University of Virginia

Study Description

Brief Summary:

The objective of the study is to assess efficacy and safety of a closed loop system (t:slim X2 with Control-IQ Technology) in a large randomized controlled trial.

Condition or disease	Intervention/treatment	Phase
Type 1 Diabetes Mellitus	Device: t:slim X2 with Control-IQ Technology & Dexcom G6 CGM; Device: Sensor-augmented pump (SAP)	Not Applicable

Detailed Description:

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 to 8 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 2:1 to the use of closed-loop control (CLC group) using t:slim X2 with Control-IQ Technology vs. SAP for 6 months.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 168 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: A randomized controlled trial of 6 month at home closed loop system vs. sensor-augmented pump.
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Pivotal Study of t:Slim X2 With Control-IQ Technology
• Actual Study Start Date: June 28, 2018
• Actual Primary Completion Date: April 8, 2019
• Actual Study Completion Date: April 8, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Closed Loop Control (CLC); Participants randomized to the closed loop control (CLC) arm will use the t:slim X2 with Control-IQ Technology & Dexcom G6 CGM for 6 months.	Device: t:slim X2 with Control-IQ Technology & Dexcom G6 CGM; Participants will use the Tandem t:slim X2 with Control-IQ Technology & Dexcom G6 CGM for 6 months at home.
Active Comparator: Sensor-Augmented Pump (SAP); Participants randomized to sensor-augmented pump (SAP) will use an insulin pump with no automated insulin delivery and a study CGM (Dexcom G6) for 6 months.	Device: Sensor-augmented pump (SAP); Participants will use an insulin pump with no automated insulin delivery and a study CGM (Dexcom G6) for 6 months at home. Pump-users at the time of enrollment will use their personal pump in this arm. Multiple daily injection (MDI) users at the time of enrollment will use a t:slim X2 insulin pump without Control-IQ technology.

Outcome Measures

Primary Outcome Measures :

1. Time in Target Range [ Time Frame: 26 weeks ]
   The primary outcome is time in target range 70-180 mg/dL measured by CGM in CLC group vs. SAP group.

Secondary Outcome Measures :

1. CGM Time Above 180 [ Time Frame: 26 weeks ]
   CGM-measured % above 180 mg/dL
2. CGM Mean Glucose [ Time Frame: 26 weeks ]
   CGM-measured mean glucose
3. HbA1c at 26 Weeks [ Time Frame: 26 weeks ]
   Hemoglobin A1c measured at 26 weeks
4. CGM Time Below 70 [ Time Frame: 26 weeks ]
   CGM-measured % below 70 mg/dL
5. CGM Time Below 54 [ Time Frame: 26 weeks ]
   CGM-measured % below 54 mg/dL
6. CGM Time in Range 70-140 mg/dL [ Time Frame: 26 weeks ]
   CGM-measured % in range 70-140 mg/dL
7. Coefficient of Variability [ Time Frame: 26 weeks ]
   CGM measured glucose variability measured with the coefficient of variation (CV)
8. Standard Deviation of CGM [ Time Frame: 26 weeks ]
   CGM measured glucose variability measured with the standard deviation (SD)
9. CGM Time Below 60 [ Time Frame: 26 weeks ]
   CGM-measured % below 60 mg/dL
10. LBGI [ Time Frame: 26 weeks ]
    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)
11. CGM Hypoglycemia Events [ Time Frame: 26 weeks ]
    CGM-measured events of at least 15 consecutive minutes <70mg/dL per week
12. CGM Time >250 [ Time Frame: 26 weeks ]
    CGM-measured % >250 mg/dL
13. CGM Time >300 [ Time Frame: 26 weeks ]
    CGM-measured % >300 mg/dL
14. HBGI [ Time Frame: 26 weeks ]
    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)
15. Number of Participants With HbA1c <7.0% at 26 Weeks [ Time Frame: 26 weeks ]
    Number of participants HbA1c <7.0% at 26 weeks
16. Number of Participants With HbA1c <7.5% at 26 Weeks [ Time Frame: 26 weeks ]
    Number of Participants with HbA1c <7.5% at 26 weeks
17. Number of Participants With HbA1c Improvement From Baseline to 26 Weeks >0.5% [ Time Frame: 26 weeks ]
    HbA1c improvement from baseline to 26 weeks >0.5%
18. Number of Participants With HbA1c Improvement From Baseline to 26 Weeks >1.0% [ Time Frame: 26 weeks ]
    HbA1c improvement from baseline to 26 weeks >1.0%
19. HbA1c Relative Improvement From Baseline to 26 Weeks >10% [ Time Frame: 26 weeks ]
    HbA1c relative improvement from baseline to 26 weeks >10%
20. Number of Participants With HbA1c Improvement From Baseline to 26 Weeks >1.0% or HbA1c <7.0% at 26 Weeks [ Time Frame: 26 weeks ]
    HbA1c improvement from baseline to 26 weeks >1.0% or HbA1c <7.0% at 26 weeks
21. HFS-II [ Time Frame: 26 weeks ]
    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. The teen survey has a total of 25 items and the range of Total scores is 0 to 100. The parent version of the survey has a total of 26 items with Total scores that range from 0 to 108.
22. Hyperglycemia Avoidance Scale [ Time Frame: 26 weeks ]
    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.
23. Diabetes Distress Scale [ Time Frame: 26 weeks ]
    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.
24. Hypoglycemia Confidence Scale [ Time Frame: 26 weeks ]
    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.
25. Clarke Hypoglycemia Awareness Scores [ Time Frame: 26 weeks ]
    Clarke Hypoglycemia Awareness Scores (0-7 score with higher scores associated with impaired awareness)
26. INSPIRE Survey Scores [ Time Frame: 26 weeks ]
    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.
27. System Usability Scores (SUS) [ Time Frame: 26 weeks ]
    System Usability Scores (SUS)-composite score from 0 to 100 with higher scores indicate better perceived usability
28. Technology Acceptance Questionnaire [ Time Frame: 26 weeks ]
    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.
29. Total Daily Insulin [ Time Frame: 26 weeks ]
    Total Daily Insulin (units)
30. Basal:Bolus Insulin Ratio [ Time Frame: 26 weeks ]
    Basal:Bolus Insulin Ratio
31. Weight [ Time Frame: 26 weeks ]
    Weight (kg)
32. BMI [ Time Frame: 26 weeks ]
    Body Mass Index (BMI) kg/m^2

Other Outcome Measures:

1. Number of Participants With Severe Hypoglycemia (Per Protocol) [ Time Frame: 26 weeks ]
   Severe hypoglycemia (per protocol)
2. Number of Participants With Diabetic Ketoacidosis (Per Protocol) [ Time Frame: 26 weeks ]
   Diabetic ketoacidosis (per protocol)
3. Ketone Events Defined as Day With Ketone Level >1.0 mmol/L [ Time Frame: 26 weeks ]
   Ketone events defined as day with ketone level >1.0 mmol/L
4. CGM-measured Hypoglycemic Events (>15 Minutes With Glucose Concentration <54 mg/dL) [ Time Frame: 26 weeks ]
   CGM-measured hypoglycemic events (>15 minutes with glucose concentration <54 mg/dL)
5. CGM-measured Hyperglycemic Events (>15 Minutes With Glucose Concentration >300 mg/dL) [ Time Frame: 26 weeks ]
   CGM-measured hyperglycemic events (>15 minutes with glucose concentration >300 mg/dL)
6. BG-measured Hypoglycemic Events (One BG Record <54 mg/dL) [ Time Frame: 26 weeks ]
   BG-measured hypoglycemic events (one BG record <54 mg/dL)
7. BG-measured Hyperglycemic Events (One BG Record >350 mg/dL) [ Time Frame: 26 weeks ]
   BG-measured hyperglycemic events (one BG record >350 mg/dL)
8. Worsening of HbA1c From Baseline to 26 Weeks by >0.5% [ Time Frame: 26 weeks ]
   Worsening of HbA1c from baseline to 26 weeks by >0.5%
9. Other Serious Adverse Events (SAE) and Serious Adverse Device Events (SADE) [ Time Frame: 26 weeks ]
   Other serious adverse events (SAE) and serious adverse device events (SADE)
10. Adverse Device Effects (ADE) [ Time Frame: 26 weeks ]
    Adverse device effects (ADE)
11. Unanticipated Adverse Device Effects (UADE) [ Time Frame: 26 weeks ]
    Unanticipated adverse device effects (UADE)
12. Number of Participants With SH Events [ Time Frame: 26 weeks ]
    For this outcome, mean +/- SD or summary statistics appropriate to the distribution will be tabulated by treatment group
13. SH Event Rate Per 100 Person-years [ Time Frame: 26 weeks ]
    For this outcome, severe hypoglycemia event rate per 100 person-years will be calculated as a rate.
14. Number of Participants With DKA Events [ Time Frame: 26 weeks ]
    For this outcome, number of participants with diabetic ketoacidosis (DKA) will be tabulated.
15. DKA Event Rate Per 100 Person-years [ Time Frame: 26 weeks ]
    For this outcome, the diabetic ketoacidosis event rate per 100 person-years will be calculated as a rate.
16. Any Adverse Event Rate Per 100 Person-years [ Time Frame: 26 weeks ]
    For this outcome, the adverse event rate per 100 person-years calculated as a rate.

Eligibility Criteria

• Ages Eligible for Study: 14 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least one year and using insulin for at least 1 year.
2. Familiarity and use of a carbohydrate ratio for meal boluses.
3. Age ≥14.0 years old.
4. 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.
5. 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.
6. Willingness to suspend use of any personal CGM for the duration of the clinical trial once the study CGM is in use.
7. Willingness to use a regular insulin pump during the study with no automatic insulin adjustment based on glucose level when assigned to participate in an SAP group
8. Investigator has confidence that the participant can successfully operate all study devices and is capable of adhering to the protocol.
9. 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.
10. Total daily insulin dose (TDD) at least 10 U/day.
11. Willingness not to start any new non-insulin glucose-lowering agent during the course of the trial.

Exclusion Criteria

1. Concurrent use of any non-insulin glucose-lowering agent other than metformin (including GLP-1 agonists, Symlin, DPP-4 inhibitors, SGLT-2 inhibitors, sulfonylureas).
2. Hemophilia or any other bleeding disorder.
3. A condition, which in the opinion of the investigator or designee, would put the participant or study at risk.
4. Participation in another pharmaceutical or device trial at the time of enrollment or during the study.
5. Employed by, or having immediate family members employed by Tandem Diabetes Care, 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.

Contacts and Locations

Locations

United States, California

Sansum Diabetes Research Institute

Santa Barbara, California, United States, 93105

Stanford University

Stanford, California, United States, 94304

United States, Colorado

Barbara Davis Center, University of Colorado

Aurora, Colorado, United States, 80045

United States, Massachusetts

Harvard University (Joslin Diabetes Center)

Boston, Massachusetts, United States, 02215

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55902

United States, New York

Icahn School of Medicine at Mount Sinai

New York, New York, United States, 10029

United States, Virginia

University of Virginia Center for Diabetes Technology

Charlottesville, Virginia, United States, 22903

Sponsors and Collaborators

University of Virginia

Jaeb Center for Health Research

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Tandem Diabetes Care, Inc.

DexCom, Inc.

Roche Diagnostics

Investigators

• Principal Investigator: Sue A. Brown, MD; University of Virginia

  Study Documents (Full-Text)

Documents provided by Sue Brown, University of Virginia:

Study Protocol  [PDF] November 5, 2018

Statistical Analysis Plan  [PDF] October 12, 2018

Informed Consent Form  [PDF] August 31, 2018

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kanapka LG, Lum JW, Beck RW. Insulin Pump Infusion Set Failures Associated with Prolonged Hyperglycemia: Frequency and Relationship to Age and Type of Infusion Set During 22,741 Infusion Set Wears. Diabetes Technol Ther. 2022 Jun;24(6):396-402. doi: 10.1089/dia.2021.0548. Epub 2022 Feb 23.

Ekhlaspour L, Town M, Raghinaru D, Lum JW, Brown SA, Buckingham BA. Glycemic Outcomes in Baseline Hemoglobin A1C Subgroups in the International Diabetes Closed-Loop Trial. Diabetes Technol Ther. 2022 Aug;24(8):588-591. doi: 10.1089/dia.2021.0524. Epub 2022 Feb 8.

Kudva YC, Laffel LM, Brown SA, Raghinaru D, Pinsker JE, Ekhlaspour L, Levy CJ, Messer LH, Kovatchev BP, Lum JW, Beck RW, Gonder-Frederick L; iDCL Trial Research Group. Patient-Reported Outcomes in a Randomized Trial of Closed-Loop Control: The Pivotal International Diabetes Closed-Loop Trial. Diabetes Technol Ther. 2021 Oct;23(10):673-683. doi: 10.1089/dia.2021.0089.

Isganaitis E, Raghinaru D, Ambler-Osborn L, Pinsker JE, Buckingham BA, Wadwa RP, Ekhlaspour L, Kudva YC, Levy CJ, Forlenza GP, Beck RW, Kollman C, Lum JW, Brown SA, Laffel LM; iDCL Trial Research Group. Closed-Loop Insulin Therapy Improves Glycemic Control in Adolescents and Young Adults: Outcomes from the International Diabetes Closed-Loop Trial. Diabetes Technol Ther. 2021 May;23(5):342-349. doi: 10.1089/dia.2020.0572. Epub 2021 Jan 21.

O'Malley G, Messer LH, Levy CJ, Pinsker JE, Forlenza GP, Isganaitis E, Kudva YC, Ekhlaspour L, Raghinaru D, Lum J, Brown SA; iDCL Trial Research Group. Clinical Management and Pump Parameter Adjustment of the Control-IQ Closed-Loop Control System: Results from a 6-Month, Multicenter, Randomized Clinical Trial. Diabetes Technol Ther. 2021 Apr;23(4):245-252. doi: 10.1089/dia.2020.0472.

Brown SA, Kovatchev BP, Raghinaru D, Lum JW, Buckingham BA, Kudva YC, Laffel LM, Levy CJ, Pinsker JE, Wadwa RP, Dassau E, Doyle FJ 3rd, Anderson SM, Church MM, Dadlani V, Ekhlaspour L, Forlenza GP, Isganaitis E, Lam DW, Kollman C, Beck RW; iDCL Trial Research Group. Six-Month Randomized, Multicenter Trial of Closed-Loop Control in Type 1 Diabetes. N Engl J Med. 2019 Oct 31;381(18):1707-1717. doi: 10.1056/NEJMoa1907863. Epub 2019 Oct 16.

• Responsible Party: Sue Brown, Principal Investigator, University of Virginia
• ClinicalTrials.gov Identifier: NCT03563313
• Other Study ID Numbers: DCLP3; UC4DK108483 ( U.S. NIH Grant/Contract )
• First Posted: June 20, 2018
• Results First Posted: April 28, 2020
• Last Update Posted: April 28, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Will follow the NIH Data Sharing Policy and Implementation Guidance on sharing research resources for research purposes to qualified individuals within the scientific community.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)
• Time Frame: Generally, data will be made available after the primary publications of each study.

Access Criteria

The Data Sharing Agreements will be formulated by the Steering Committee in collaboration with the NIH Project Scientist Program Official.

In addition, under special arrangements, complete data sets will be provided to industry partners who would use the data for regulatory clearance (PMA - pre-market approval) of the tested artificial pancreas system. This will be done in response to the specific requirements of RFA-DK-14-024 for this project to "…generate data able to satisfy safety and efficacy requirements by regulatory agencies regarding the clinical testing of artificial pancreas device systems" in the target population of people with type 1 diabetes.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

Keywords provided by Sue Brown, University of Virginia:

Artificial Pancreas (AP); Type 1 Diabetes Mellitus; Insulin Pump; Continuous Glucose Monitor (CGM); Closed Loop Control (CLC); Sensor-Augmented Pump (SAP)

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases