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

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

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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Device: t:slim X2 with Control-IQ Technology & Dexcom G6 CGM; Device: Sensor-augmented pump (SAP)

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 Type: Interventional
• Enrollment (Actual): 168
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Santa Barbara, California, United States, 93105
      • Sansum Diabetes Research Institute
    • Stanford, California, United States, 94304
      • Stanford University
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Barbara Davis Center, University of Colorado
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Harvard University (Joslin Diabetes Center)
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Center for Diabetes Technology

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CGM Time Above 180	CGM-measured % above 180 mg/dL	26 weeks
CGM Mean Glucose	CGM-measured mean glucose	26 weeks
HbA1c at 26 Weeks	Hemoglobin A1c measured at 26 weeks	26 weeks
CGM Time Below 70	CGM-measured % below 70 mg/dL	26 weeks
CGM Time Below 54	CGM-measured % below 54 mg/dL	26 weeks
CGM Time in Range 70-140 mg/dL	CGM-measured % in range 70-140 mg/dL	26 weeks
Coefficient of Variability	CGM measured glucose variability measured with the coefficient of variation (CV)	26 weeks
Standard Deviation of CGM	CGM measured glucose variability measured with the standard deviation (SD)	26 weeks
CGM Time Below 60	CGM-measured % below 60 mg/dL	26 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)	26 weeks
CGM Hypoglycemia Events	CGM-measured events of at least 15 consecutive minutes <70mg/dL per week	26 weeks
CGM Time >250	CGM-measured % >250 mg/dL	26 weeks
CGM Time >300	CGM-measured % >300 mg/dL	26 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)	26 weeks
Number of Participants With HbA1c <7.0% at 26 Weeks	Number of participants HbA1c <7.0% at 26 weeks	26 weeks
Number of Participants With HbA1c <7.5% at 26 Weeks	Number of Participants with HbA1c <7.5% at 26 weeks	26 weeks
Number of Participants With HbA1c Improvement From Baseline to 26 Weeks >0.5%	HbA1c improvement from baseline to 26 weeks >0.5%	26 weeks
Number of Participants With HbA1c Improvement From Baseline to 26 Weeks >1.0%	HbA1c improvement from baseline to 26 weeks >1.0%	26 weeks
HbA1c Relative Improvement From Baseline to 26 Weeks >10%	HbA1c relative improvement from baseline to 26 weeks >10%	26 weeks
Number of Participants With HbA1c Improvement From Baseline to 26 Weeks >1.0% or HbA1c <7.0% at 26 Weeks	HbA1c improvement from baseline to 26 weeks >1.0% or HbA1c <7.0% at 26 weeks	26 weeks
HFS-II	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.	26 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.	26 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.	26 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.	26 weeks
Clarke Hypoglycemia Awareness Scores	Clarke Hypoglycemia Awareness Scores (0-7 score with higher scores associated with impaired awareness)	26 weeks
INSPIRE Survey Scores	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.	26 weeks
System Usability Scores (SUS)	System Usability Scores (SUS)-composite score from 0 to 100 with higher scores indicate better perceived usability	26 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.	26 weeks
Total Daily Insulin	Total Daily Insulin (units)	26 weeks
Basal:Bolus Insulin Ratio	Basal:Bolus Insulin Ratio	26 weeks
Weight	Weight (kg)	26 weeks
BMI	Body Mass Index (BMI) kg/m^2	26 weeks

Other Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Virginia
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); DexCom, Inc.; Tandem Diabetes Care, Inc.; Jaeb Center for Health Research; Roche Diagnostics
• Investigators: Principal Investigator: Sue A. Brown, MD, University of Virginia

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2018
• Primary Completion (Actual): April 8, 2019
• Study Completion (Actual): April 8, 2019

Study Registration Dates

• First Submitted: June 7, 2018
• First Submitted That Met QC Criteria: June 18, 2018
• First Posted (Actual): June 20, 2018

Study Record Updates

• Last Update Posted (Actual): April 28, 2020
• Last Update Submitted That Met QC Criteria: April 17, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Type 1 Diabetes Mellitus; Artificial Pancreas (AP); Continuous Glucose Monitor (CGM); Closed Loop Control (CLC); Insulin Pump; Sensor-Augmented Pump (SAP)
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: DCLP3; UC4DK108483 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD 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.
• IPD Sharing Time Frame: Generally, data will be made available after the primary publications of each study.

IPD Sharing 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.

• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes