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

Type 1 Diabetes Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04796779
• Other study ID #: 200433
• Secondary ID: 1U01DK127551-01R
• Status: Completed
• Phase: N/A
• Start date: April 21, 2021
• Est. completion date: July 31, 2022

Study information

• Verified date: June 2023
• Source: University of Virginia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 102
• Est. completion date: July 31, 2022
• Est. primary completion date: April 12, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 24 Months to 71 Months

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

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.
• 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).
• 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.

Locations

Country	Name	City	State
United States	Barbara Davis Center, University of Colorado	Aurora	Colorado
United States	University of Virginia Center for Diabetes Technology	Charlottesville	Virginia
United States	Stanford University	Stanford	California

Sponsors (4)

Lead Sponsor	Collaborator
Marc Breton	Jaeb Center for Health Research, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Tandem Diabetes Care, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percent Above 180 mg/dL	percent above 180 mg/dL	13 weeks
Other	Percent in Range 70-140 mg/dL	percent in range 70-140 mg/dL	13 weeks
Other	Glucose Variability Measured With the Coefficient of Variation (CV)	glucose variability measured with the coefficient of variation (CV)	13 weeks
Other	Glucose Variability Measured With the Standard Deviation (SD)	glucose variability measured with the standard deviation (SD)	13 weeks
Other	CGM-measured Percent <60 mg/dL	CGM-measured percent <60 mg/dL	13 weeks
Other	Low Blood Glucose Index (LBGI)*	low blood glucose index (LBGI)*	13 weeks
Other	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
Other	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
Other	Percent >300 mg/dL	percent >300 mg/dL	13 weeks
Other	High Blood Glucose Index (HBGI)*	high blood glucose index (HBGI)*	13 weeks
Other	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
Other	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
Other	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
Other	HbA1c <7.0 Percent at 13 Weeks	HbA1c <7.0 percent at 13 weeks	13 weeks
Other	HbA1c <7.5 Percent at 13 Weeks	HbA1c <7.5 percent at 13 weeks	13 weeks
Other	HbA1c Improvement From Baseline to 13 Weeks >0.5 Percent	HbA1c improvement from baseline to 13 weeks >0.5 percent	13 weeks
Other	HbA1c Improvement From Baseline to 13 Weeks >1.0 Percent	HbA1c improvement from baseline to 13 weeks >1.0 percent	13 weeks
Other	HbA1c Relative Improvement From Baseline to 13 Weeks >10 Percent	HbA1c relative improvement from baseline to 13 weeks >10 percent	13 weeks
Other	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
Other	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
Other	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
Other	Number of Other Serious Adverse Events	Number of other serious adverse events (SAEs other than SH events and DKA events)	13 weeks
Other	Any Adverse Event Rate	Any adverse event rate	13 weeks
Other	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
Other	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
Other	Adverse Device Effects (ADE)	Adverse device effects (ADE) in intervention group only	13 weeks
Other	Serious Adverse Device Events (SADE)	Serious adverse device events (SADE) in intervention group only	13 weeks
Other	Unanticipated Adverse Device Effects (UADE)	Unanticipated adverse device effects (UADE) in intervention group only	13 weeks
Other	Total Daily Insulin (Units/kg)	Total daily insulin (units/kg)	13 weeks
Other	Percentage of Total Insulin Delivered Via Basal	Percentage of total insulin delivered via basal	13 weeks
Other	Weight	Weight	13 weeks
Other	Body Mass Index (BMI)	Body Mass Index (BMI)	13 weeks
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	CGM-measured % <54 mg/dL Overnight (All Challenge Types)	CGM-measured % <54 mg/dL overnight (all challenge types)	8 hours
Other	CGM-measured % <70 mg/dL Overnight (All Challenge Types)	CGM-measured % <70 mg/dL overnight (all challenge types)	8 hours
Other	CGM-measured % >180 mg/dL Overnight (All Challenge Types)	CGM-measured % >180 mg/dL overnight (all challenge types)	8 hours
Other	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
Other	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
Other	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
Other	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
Primary	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	CGM-measured Percent Above 250 mg/dL	Percentage of time with a glucose above 250 mg/dL as measured by CGM	13 weeks
Secondary	CGM-measured Mean Glucose	Average glucose value measured by CGM	13 weeks
Secondary	HbA1c at 13 Weeks	HbA1c at 13 weeks	13 weeks
Secondary	CGM-measured Percent Below 70 mg/dL	Percentage of time with glucose below 70 mg/dL as measured by CGM	13 weeks
Secondary	CGM-measured Percent Below 54 mg/dL	Percentage of time with glucose below 54 mg/dL as measured by CGM	13 weeks

External Links

•   Study Results