Clinical trial NCT03563313: The International Diabetes Closed Loop (iDCL) Trial: Clinical Acceptance of the Artificial Pancreas
Official title: A Pivotal Study of t:Slim X2 With Control-IQ Technology
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetes Mellitus
Keywords: Artificial Pancreas (AP)
Type 1 Diabetes Mellitus
Insulin Pump
Continuous Glucose Monitor (CGM)
Closed Loop Control (CLC)
Sensor-Augmented Pump (SAP)
Lead sponsor: University of Virginia
Sponsor class: OTHER
Collaborators: name: Jaeb Center for Health Research
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Tandem Diabetes Care, Inc.
name: DexCom, Inc.
name: Roche Diagnostics GmbH
First posted: 2018-06-20
Enrollment: 168
Sex: ALL
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomized controlled trial of 6 month at home closed loop system vs. sensor-augmented pump.
Primary purpose: OTHER

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.

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.

Eligibility 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.

Primary outcomes:
measure: Time in Target Range
timeFrame: 26 weeks
Secondary outcomes:
measure: CGM Time Above 180
timeFrame: 26 weeks
measure: CGM Mean Glucose
timeFrame: 26 weeks
measure: HbA1c at 26 Weeks
timeFrame: 26 weeks
measure: CGM Time Below 70
timeFrame: 26 weeks
measure: CGM Time Below 54
timeFrame: 26 weeks
measure: CGM Time in Range 70-140 mg/dL
timeFrame: 26 weeks
measure: Coefficient of Variability
timeFrame: 26 weeks
measure: Standard Deviation of CGM
timeFrame: 26 weeks
measure: CGM Time Below 60
timeFrame: 26 weeks
measure: LBGI
timeFrame: 26 weeks
measure: CGM Hypoglycemia Events
timeFrame: 26 weeks
measure: CGM Time >250
timeFrame: 26 weeks
measure: CGM Time >300
timeFrame: 26 weeks
measure: HBGI
timeFrame: 26 weeks
measure: Number of Participants With HbA1c <7.0% at 26 Weeks
timeFrame: 26 weeks
measure: Number of Participants With HbA1c <7.5% at 26 Weeks
timeFrame: 26 weeks
measure: Number of Participants With HbA1c Improvement From Baseline to 26 Weeks >0.5%
timeFrame: 26 weeks
measure: Number of Participants With HbA1c Improvement From Baseline to 26 Weeks >1.0%
timeFrame: 26 weeks
measure: HbA1c Relative Improvement From Baseline to 26 Weeks >10%
timeFrame: 26 weeks
measure: Number of Participants With HbA1c Improvement From Baseline to 26 Weeks >1.0% or HbA1c <7.0% at 26 Weeks
timeFrame: 26 weeks
measure: HFS-II
timeFrame: 26 weeks
measure: Hyperglycemia Avoidance Scale
timeFrame: 26 weeks
measure: Diabetes Distress Scale
timeFrame: 26 weeks
measure: Hypoglycemia Confidence Scale
timeFrame: 26 weeks
measure: Clarke Hypoglycemia Awareness Scores
timeFrame: 26 weeks
measure: INSPIRE Survey Scores
timeFrame: 26 weeks
measure: System Usability Scores (SUS)
timeFrame: 26 weeks
measure: Technology Acceptance Questionnaire
timeFrame: 26 weeks
measure: Total Daily Insulin
timeFrame: 26 weeks
measure: Basal:Bolus Insulin Ratio
timeFrame: 26 weeks
measure: Weight
timeFrame: 26 weeks
measure: BMI
timeFrame: 26 weeks
Other outcomes:
measure: Number of Participants With Severe Hypoglycemia (Per Protocol)
timeFrame: 26 weeks
measure: Number of Participants With Diabetic Ketoacidosis (Per Protocol)
timeFrame: 26 weeks
measure: Ketone Events Defined as Day With Ketone Level >1.0 mmol/L
timeFrame: 26 weeks
measure: CGM-measured Hypoglycemic Events (>15 Minutes With Glucose Concentration <54 mg/dL)
timeFrame: 26 weeks
measure: CGM-measured Hyperglycemic Events (>15 Minutes With Glucose Concentration >300 mg/dL)
timeFrame: 26 weeks
measure: BG-measured Hypoglycemic Events (One BG Record <54 mg/dL)
timeFrame: 26 weeks
measure: BG-measured Hyperglycemic Events (One BG Record >350 mg/dL)
timeFrame: 26 weeks
measure: Worsening of HbA1c From Baseline to 26 Weeks by >0.5%
timeFrame: 26 weeks
measure: Other Serious Adverse Events (SAE) and Serious Adverse Device Events (SADE)
timeFrame: 26 weeks
measure: Adverse Device Effects (ADE)
timeFrame: 26 weeks
measure: Unanticipated Adverse Device Effects (UADE)
timeFrame: 26 weeks
measure: Number of Participants With SH Events
timeFrame: 26 weeks
measure: SH Event Rate Per 100 Person-years
timeFrame: 26 weeks
measure: Number of Participants With DKA Events
timeFrame: 26 weeks
measure: DKA Event Rate Per 100 Person-years
timeFrame: 26 weeks
measure: Any Adverse Event Rate Per 100 Person-years
timeFrame: 26 weeks
Locations:
city: Santa Barbara
country: United States
facility: Sansum Diabetes Research Institute
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: Barbara Davis Center, University of Colorado
state: Colorado
city: Boston
country: United States
facility: Harvard University (Joslin Diabetes Center)
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Charlottesville
country: United States
facility: University of Virginia Center for Diabetes Technology
state: Virginia
Study officials:
affiliation: University of Virginia
name: Sue A. Brown, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.