The Pediatric Artificial Pancreas (PEDAP) Trial of Control-IQ Technology in Young Children in Type 1 Diabetes

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

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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Device: Tandem t:slim X2 with Control-IQ Technology Pro; Device: Tandem t:slim X2 with Control-IQ Technology V1.5; Device: Standard Care (SC)

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.

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94304
      • Stanford University
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Barbara Davis Center, University of Colorado
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Center for Diabetes Technology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 5 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CLC Group; Participants who skip or successfully complete the run-in will be randomly assigned 2:1 to the use of closed-loop control (CLC group) system using Tandem t:slim X2 with Control-IQ Technology vs Standard of Care (SC group) for 3 weeks. Participants randomized to the intervention group will use the Tandem t:slim X2 with Control-IQ Technology v1.0 during the first 13 weeks of the study (RCT phase, weeks 1-13) and then use Tandem t:slim X2 insulin pump with Control-IQ Technology v1.5 for the remaining 13 weeks of the study (extension phase, weeks 14-26).	Device: Tandem t:slim X2 with Control-IQ Technology Pro; The Tandem t:slim X2 with Control-IQ Technology Pro is an "artificial pancreas" (AP) application that uses advanced closed loop control algorithms to automatically manage blood glucose levels for people with Type 1 Diabetes. The system modulates insulin to keep blood glucose in a targeted range. The system components include the t:slim X2 with Control-IQ Technology and the Dexcom G6 CGM. The system is very similar to the commercially available t:sli X2 with Control-IQ but modified to accept the lower weight and Total Daily Insulin of the studied population.; Device: Tandem t:slim X2 with Control-IQ Technology V1.5; The Tandem t:slim X2 with Control-IQ Technology V1.5 is an "artificial pancreas" (AP) application that uses advanced closed loop control algorithms to automatically manage blood glucose levels for people with Type 1 Diabetes. The system modulates insulin to keep blood glucose in a targeted range. The system components include the t:slim X2 with Control-IQ Technology and the Dexcom G6 CGM. The system is derived from the commercially available t:slim X2 with Control-IQ, with additional features.
Active Comparator: SC Group; Participants who skip or successfully complete the run-in will be randomly assigned 2:1 to the use of closed-loop control (CLC group) system using Tandem t:slim X2 with Control-IQ Technology vs Standard of Care (SC group) for 3 weeks. Participants randomized to the SC group will use their existing insulin therapy in conjunction with study Dexcom G6 CGM during the first 13 weeks of the study (RCT phase, weeks 1-13). The SC group will then transition to using the Tandem t:slim X2 insulin pump with Control-IQ Technology v1.5 and study Dexcom G6 CGM for the remaining 13 weeks of the study (weeks 14-26).	Device: Tandem t:slim X2 with Control-IQ Technology V1.5; The Tandem t:slim X2 with Control-IQ Technology V1.5 is an "artificial pancreas" (AP) application that uses advanced closed loop control algorithms to automatically manage blood glucose levels for people with Type 1 Diabetes. The system modulates insulin to keep blood glucose in a targeted range. The system components include the t:slim X2 with Control-IQ Technology and the Dexcom G6 CGM. The system is derived from the commercially available t:slim X2 with Control-IQ, with additional features.; Device: Standard Care (SC); Standard of Care consists in the participant existing insulin therapy (prior to enrollment) in conjunction with a study Dexcom G6 CGM. Existing insulin therapies are defined as multiple daily injections of insulin (MDI) or use of an insulin pump without hybrid closed-loop control capabilities (low-glucose suspend or predictive low-glucose suspend functionality is permitted).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time in Range	Time in range is the amount of time spent in the target glucose range-between 70 and 180 mg/dL-as measured by CGM	13 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CGM-measured Percent Above 250 mg/dL	Percentage of time with a glucose above 250 mg/dL as measured by CGM	13 weeks
CGM-measured Mean Glucose	Average glucose value measured by CGM	13 weeks
HbA1c at 13 Weeks	HbA1c at 13 weeks	13 weeks
CGM-measured Percent Below 70 mg/dL	Percentage of time with glucose below 70 mg/dL as measured by CGM	13 weeks
CGM-measured Percent Below 54 mg/dL	Percentage of time with glucose below 54 mg/dL as measured by CGM	13 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight	Weight	13 weeks
Body Mass Index (BMI)	Body Mass Index (BMI)	13 weeks
Percent Above 180 mg/dL	percent above 180 mg/dL	13 weeks
Percent in Range 70-140 mg/dL	percent in range 70-140 mg/dL	13 weeks
Glucose Variability Measured With the Coefficient of Variation (CV)	glucose variability measured with the coefficient of variation (CV)	13 weeks
Glucose Variability Measured With the Standard Deviation (SD)	glucose variability measured with the standard deviation (SD)	13 weeks
CGM-measured Percent <60 mg/dL	CGM-measured percent <60 mg/dL	13 weeks
Low Blood Glucose Index (LBGI)*	low blood glucose index (LBGI)*	13 weeks
Hypoglycemic Events (Defined as at Least 15 Consecutive Minutes <54 mg/dL)	hypoglycemic events (defined as at least 15 consecutive minutes <54 mg/dL)	13 weeks
Hyperglycemic Events (Defined as at Least 90 Consecutive Minutes >300 mg/dL)	hyperglycemic events (defined as at least 90 consecutive minutes >300 mg/dL)	13 weeks
Percent >300 mg/dL	percent >300 mg/dL	13 weeks
High Blood Glucose Index (HBGI)*	high blood glucose index (HBGI)*	13 weeks
Percent in Range 70-180 mg/dL Improvement From Baseline to 13 Weeks ≥5 Percent	percent in range 70-180 mg/dL improvement from baseline to 13 weeks ≥5 percent	13 weeks
Percent in Range 70-180 mg/dL Improvement From Baseline to 13 Weeks ≥10 Percent	percent in range 70-180 mg/dL improvement from baseline to 13 weeks ≥10 percent	13 weeks
Percent Time in Range 70-180 mg/dL >70 Percent and Percent Time <70 mg/dL <4 Percent	percent time in range 70-180 mg/dL >70 percent and percent time <70 mg/dL <4 percent	13 weeks
HbA1c <7.0 Percent at 13 Weeks	HbA1c <7.0 percent at 13 weeks	13 weeks
HbA1c <7.5 Percent at 13 Weeks	HbA1c <7.5 percent at 13 weeks	13 weeks
HbA1c Improvement From Baseline to 13 Weeks >0.5 Percent	HbA1c improvement from baseline to 13 weeks >0.5 percent	13 weeks
HbA1c Improvement From Baseline to 13 Weeks >1.0 Percent	HbA1c improvement from baseline to 13 weeks >1.0 percent	13 weeks
HbA1c Relative Improvement From Baseline to 13 Weeks >10 Percent	HbA1c relative improvement from baseline to 13 weeks >10 percent	13 weeks
HbA1c Absolute Improvement From Baseline to 13 Weeks >1.0 Percent or HbA1c <7.0 Percent at 13 Weeks	HbA1c absolute improvement from baseline to 13 weeks >1.0 percent or HbA1c <7.0 percent at 13 weeks	13 weeks
Number of Severe Hypoglycemic (SH) Events and SH Event Rate Per 100 Person-years	Number of SH events and SH event rate per 100 person-years	13 weeks
Number of Diabetic Ketoacidosis (DKA) Events and DKA Event Rate Per 100 Person-years	Number of DKA events and DKA event rate per 100 person-years	13 weeks
Number of Other Serious Adverse Events	Number of other serious adverse events (SAEs other than SH events and DKA events)	13 weeks
Any Adverse Event Rate	Any adverse event rate	13 weeks
Number of Calendar Days With Any Ketone Level ≥1.0 mmol/L (if ≥5 Total Calendar Days Combined)	Number of calendar days with any ketone level ≥1.0 mmol/L (if ≥5 total calendar days combined)	13 weeks
Worsening of HbA1c From Baseline to 13 Weeks by >0.5 Percent	Worsening of HbA1c from baseline to 13 weeks by >0.5 percent	13 weeks
Adverse Device Effects (ADE)	Adverse device effects (ADE) in intervention group only	13 weeks
Serious Adverse Device Events (SADE)	Serious adverse device events (SADE) in intervention group only	13 weeks
Unanticipated Adverse Device Effects (UADE)	Unanticipated adverse device effects (UADE) in intervention group only	13 weeks
Total Daily Insulin (Units/kg)	Total daily insulin (units/kg)	13 weeks
Percentage of Total Insulin Delivered Via Basal	Percentage of total insulin delivered via basal	13 weeks
PedsQL Diabetes Module - Total Score and 5 Subscales	PedsQL Diabetes Module - total score and 5 subscales: Diabetes, Treatment 1, Treatment 2, Worry, Communication	13 weeks
Pediatric Inventory for Parents (PIP) 2 Domains Each With a Total Score and 4 Subscales for (5x2=10 Difference Scores)	Pediatric Inventory for Parents (PIP) 2 domains each with a total score and 4 subscales for (5x2=10 difference scores): Frequency (Total Score, Communication, Medical Care, Role Function, Emotional Functioning), Difficulty ( Same total + 4 subscales as above for frequency)	13 weeks
INSPIRE Survey (Insulin Delivery Systems: Perceptions, Ideas, Reflections and Expectations) (CLC Arm Only)	INSPIRE (CLC arm only) 5-point Likert scale from strongly agree to strongly disagree, along with an N/A option.	13 weeks
Pittsburgh Sleep Quality Index (PSQI) Global Score	An abbreviated 9-question version of the Pittsburgh Sleep Quality Index (PSQI), a validated tool for assessing self-reported sleep quantity and quality, will be completed by parents. Seven component scores are derived, each scored 0 (no difficulty) to 3 (severe difficulty). The component scores are summed to produce a global score (range 0 to 21). Higher scores indicate worse sleep quality.	13 weeks
Fear of Hypoglycemia Survey for Parents (HFS-P) - Total Score, 2 Subscales and 4 Factor Scores	Fear of Hypoglycemia Survey for Parents (HFS-P) - total score, 2 subscales and 4 factor scores: Behavior (avoidance, Maintain high BG), Worry (Helplessness, Social consequences)	13 weeks
Number of SH Events During, Immediately After and Overnight From the Study Challenges	Number of SH events during, immediately after and overnight from the study challenges	Up to 24 hour period
Number of Adverse Events During, Immediately After and Overnight From the Study Challenges	Number of adverse events during, immediately after and overnight from the study challenges	Up to 24 hour period
CGM-measured % <54 mg/dL Overnight (All Challenge Types)	CGM-measured % <54 mg/dL overnight (all challenge types)	8 hours
CGM-measured % <70 mg/dL Overnight (All Challenge Types)	CGM-measured % <70 mg/dL overnight (all challenge types)	8 hours
CGM-measured % >180 mg/dL Overnight (All Challenge Types)	CGM-measured % >180 mg/dL overnight (all challenge types)	8 hours
CGM-measured % <54 mg/dL During the Two Hours Immediately Following the Start of Exercise for Each Exercise-related Challenge	CGM-measured % <54 mg/dL during the two hours immediately following the start of exercise for each exercise-related challenge	2 hours
CGM-measured % <70 mg/dL During the Two Hours Immediately Following the Start of Exercise for Each Exercise-related Challenge	CGM-measured % <70 mg/dL during the two hours immediately following the start of exercise for each exercise-related challenge	2 hours
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	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	4 hours
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	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	4 hours

Collaborators and Investigators

• Sponsor: Marc Breton
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Tandem Diabetes Care, Inc.; Jaeb Center for Health Research
• Investigators: Study Director: John Lum, MS, Jaeb Center for Health Research

Publications and helpful links

General Publications

• 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.

Helpful Links

• Study Results

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2021
• Primary Completion (Actual): April 12, 2022
• Study Completion (Actual): July 31, 2022

Study Registration Dates

• First Submitted: February 15, 2021
• First Submitted That Met QC Criteria: March 10, 2021
• First Posted (Actual): March 15, 2021

Study Record Updates

• Last Update Posted (Actual): June 28, 2023
• Last Update Submitted That Met QC Criteria: June 5, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Continuous Glucose Monitor (CGM); Closed Loop Control (CLC); Insulin Pump; Control-IQ Technology; Multiple Daily Injections (MDI)
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Physiological Effects of Drugs; Trace Elements; Micronutrients; Ferrous fumarate
• Other Study ID Numbers: 200433; 1U01DK127551-01 (U.S. NIH Grant/Contract); RFA-DK-19-036 (Other Grant/Funding Number: NIDDK)

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 Supporting Information Type: STUDY_PROTOCOL; SAP; 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
• product manufactured in and exported from the U.S.: No