Clinical trial NCT04796779: The Pediatric Artificial Pancreas (PEDAP) Trial of Control-IQ Technology in Young Children in Type 1 Diabetes
Official title: The Pediatric Artificial Pancreas (PEDAP) Trial: A Randomized Controlled Comparison of the Control-IQ Technology Versus Standard of Care in Young Children in Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetes
Keywords: Control-IQ Technology
Insulin Pump
Closed Loop Control (CLC)
Continuous Glucose Monitor (CGM)
Multiple Daily Injections (MDI)
Lead sponsor: University of Virginia
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Jaeb Center for Health Research
name: Tandem Diabetes Care, Inc.
First posted: 2021-03-15
Enrollment: 102
Sex: ALL
Minimum age (years): 24
Maximum age (years): 71
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to learn whether an investigational automated insulin delivery system ("study system") for young children (2 yo to less than 6 yo) with type 1 diabetes can safely improve blood glucose (sometimes called blood sugar) control.

Detailed description: Participants will be randomized to closed loop control (CLC) system (t:slim X2 with Control-IQ Technology) or to standard of care where the children will continue to use his or her personal insulin pump or multiple daily injections. Both groups will use a continuous glucose monitor (CGM) throughout the study. The study system will also use a study insulin pump and a software algorithm to automatically give insulin and control blood glucose. This system is also sometimes called a "closed-loop" system.

This study will take about 6-7 months for the child to complete. Study visits can be completed from home via videoconference (e.g. Zoom) without visiting the clinic or in-person at the clinic.

A subset of participants will be asked to join an ancillary study with Meal Bolus and Exercise challenges during the extension phase. Data collected from the start of each of these challenges until the following morning will be excluded from the analysis of the extension phase.

Eligibility criteria: Inclusion Criteria:

1. Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least 6 months and using insulin for at least 6 months
2. Familiarity and use of a carbohydrate ratio for meal boluses.
3. Age ≥2 and \<6 years old
4. Living with one or more parent/legal guardian knowledgeable about emergency procedures for severe hypoglycemia and able to contact emergency services and study staff.
5. Investigator has confidence that the parent can successfully operate all study devices and is capable of adhering to the protocol
6. 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 a study-provided Tandem pump during the study.

   • Study will not be providing insulin; therefore, participants will need to have access to either lispro or aspart
7. Total daily insulin dose (TDD) at least 5 U/day
8. Body weight at least 20 lbs.
9. Willingness not to start any new non-insulin glucose-lowering agent during the course of the trial (see section 2.3)
10. Participant and parent(s)/guardian(s) willingness to participate in all training sessions as directed by study staff.
11. Parent/guardian proficient in reading and writing English.

Exclusion Criteria:

1. Concurrent use of any non-insulin glucose-lowering agent (including Glucagon-like peptide-1 \[GLP-1\] agonists, Symlin, Dipeptidyl peptidase-4 \[DPP-4\] inhibitors, Sodium-glucose Cotransporter-2 (SGLT-2) inhibitors, sulfonylureas).
2. Hemophilia or any other bleeding disorder
3. History of \>1 severe hypoglycemic event with seizure or loss of consciousness in the last 3 months
4. History of \>1 DKA event in the last 6 months not related to illness, infusion set failure, or initial diagnosis
5. History of chronic renal disease or currently on hemodialysis
6. History of adrenal insufficiency
7. Hypothyroidism that is not adequately treated
8. Use of oral or injectable steroids within the last 8 weeks
9. Known, ongoing adhesive intolerance
10. Plans to receive blood transfusions or erythropoietin injections during the course of the study
11. A condition, which in the opinion of the investigator or designee, would put the participant or study at risk (specified in the study procedure manual)
12. Currently using any closed-loop system, or using an insulin pump that is incompatible with use of the study CGM
13. Participation in another pharmaceutical or device trial at the time of enrollment or during the study
14. 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

Primary outcomes:
measure: Time in Range
timeFrame: 13 weeks
Secondary outcomes:
measure: CGM-measured Percent Above 250 mg/dL
timeFrame: 13 weeks
measure: CGM-measured Mean Glucose
timeFrame: 13 weeks
measure: HbA1c at 13 Weeks
timeFrame: 13 weeks
measure: CGM-measured Percent Below 70 mg/dL
timeFrame: 13 weeks
measure: CGM-measured Percent Below 54 mg/dL
timeFrame: 13 weeks
Other outcomes:
measure: Percent Above 180 mg/dL
timeFrame: 13 weeks
measure: Percent in Range 70-140 mg/dL
timeFrame: 13 weeks
measure: Glucose Variability Measured With the Coefficient of Variation (CV)
timeFrame: 13 weeks
measure: Glucose Variability Measured With the Standard Deviation (SD)
timeFrame: 13 weeks
measure: CGM-measured Percent <60 mg/dL
timeFrame: 13 weeks
measure: Low Blood Glucose Index (LBGI)*
timeFrame: 13 weeks
measure: Hypoglycemic Events (Defined as at Least 15 Consecutive Minutes <54 mg/dL)
timeFrame: 13 weeks
measure: Hyperglycemic Events (Defined as at Least 90 Consecutive Minutes >300 mg/dL)
timeFrame: 13 weeks
measure: Percent >300 mg/dL
timeFrame: 13 weeks
measure: High Blood Glucose Index (HBGI)*
timeFrame: 13 weeks
measure: Percent in Range 70-180 mg/dL Improvement From Baseline to 13 Weeks ≥5 Percent
timeFrame: 13 weeks
measure: Percent in Range 70-180 mg/dL Improvement From Baseline to 13 Weeks ≥10 Percent
timeFrame: 13 weeks
measure: Percent Time in Range 70-180 mg/dL >70 Percent and Percent Time <70 mg/dL <4 Percent
timeFrame: 13 weeks
measure: HbA1c <7.0 Percent at 13 Weeks
timeFrame: 13 weeks
measure: HbA1c <7.5 Percent at 13 Weeks
timeFrame: 13 weeks
measure: HbA1c Improvement From Baseline to 13 Weeks >0.5 Percent
timeFrame: 13 weeks
measure: HbA1c Improvement From Baseline to 13 Weeks >1.0 Percent
timeFrame: 13 weeks
measure: HbA1c Relative Improvement From Baseline to 13 Weeks >10 Percent
timeFrame: 13 weeks
measure: HbA1c Absolute Improvement From Baseline to 13 Weeks >1.0 Percent or HbA1c <7.0 Percent at 13 Weeks
timeFrame: 13 weeks
measure: Number of Severe Hypoglycemic (SH) Events and SH Event Rate Per 100 Person-years
timeFrame: 13 weeks
measure: Number of Diabetic Ketoacidosis (DKA) Events and DKA Event Rate Per 100 Person-years
timeFrame: 13 weeks
measure: Number of Other Serious Adverse Events
timeFrame: 13 weeks
measure: Any Adverse Event Rate
timeFrame: 13 weeks
measure: Number of Calendar Days With Any Ketone Level ≥1.0 mmol/L (if ≥5 Total Calendar Days Combined)
timeFrame: 13 weeks
measure: Worsening of HbA1c From Baseline to 13 Weeks by >0.5 Percent
timeFrame: 13 weeks
measure: Adverse Device Effects (ADE)
timeFrame: 13 weeks
measure: Serious Adverse Device Events (SADE)
timeFrame: 13 weeks
measure: Unanticipated Adverse Device Effects (UADE)
timeFrame: 13 weeks
measure: Total Daily Insulin (Units/kg)
timeFrame: 13 weeks
measure: Percentage of Total Insulin Delivered Via Basal
timeFrame: 13 weeks
measure: Weight
timeFrame: 13 weeks
measure: Body Mass Index (BMI)
timeFrame: 13 weeks
measure: PedsQL Diabetes Module - Total Score and 5 Subscales
timeFrame: 13 weeks
measure: Pediatric Inventory for Parents (PIP) 2 Domains Each With a Total Score and 4 Subscales for (5x2=10 Difference Scores)
timeFrame: 13 weeks
measure: INSPIRE Survey (Insulin Delivery Systems: Perceptions, Ideas, Reflections and Expectations) (CLC Arm Only)
timeFrame: 13 weeks
measure: Pittsburgh Sleep Quality Index (PSQI) Global Score
timeFrame: 13 weeks
measure: Fear of Hypoglycemia Survey for Parents (HFS-P) - Total Score, 2 Subscales and 4 Factor Scores
timeFrame: 13 weeks
measure: Number of SH Events During, Immediately After and Overnight From the Study Challenges
timeFrame: Up to 24 hour period
measure: Number of Adverse Events During, Immediately After and Overnight From the Study Challenges
timeFrame: Up to 24 hour period
measure: CGM-measured % <54 mg/dL Overnight (All Challenge Types)
timeFrame: 8 hours
measure: CGM-measured % <70 mg/dL Overnight (All Challenge Types)
timeFrame: 8 hours
measure: CGM-measured % >180 mg/dL Overnight (All Challenge Types)
timeFrame: 8 hours
measure: CGM-measured % <54 mg/dL During the Two Hours Immediately Following the Start of Exercise for Each Exercise-related Challenge
timeFrame: 2 hours
measure: CGM-measured % <70 mg/dL During the Two Hours Immediately Following the Start of Exercise for Each Exercise-related Challenge
timeFrame: 2 hours
measure: CGM-measured % >180 mg/dL During the Four Hours Following the Announced Meal, or Until the Next Meal Bolus is Given, for the Missed Meal Bolus Challenge
timeFrame: 4 hours
measure: CGM-measured % >300 mg/dL During the Four Hours Following the Announced Meal, or Until the Next Meal Bolus is Given, for the Missed Meal Bolus Challenge
timeFrame: 4 hours
Locations:
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: Charlottesville
country: United States
facility: University of Virginia Center for Diabetes Technology
state: Virginia
Study officials:
affiliation: Jaeb Center for Health Research
name: John Lum, MS
role: STUDY_DIRECTOR
References:
citation: Wadwa RP, Reed ZW, Buckingham BA, DeBoer MD, Ekhlaspour L, Forlenza GP, Schoelwer M, Lum J, Kollman C, Beck RW, Breton MD; PEDAP Trial Study Group. Trial of Hybrid Closed-Loop Control in Young Children with Type 1 Diabetes. N Engl J Med. 2023 Mar 16;388(11):991-1001. doi: 10.1056/NEJMoa2210834.