Safety of Artificial Pancreas Therapy in Preschoolers, Age 2-6

This clinical trial aims to demonstrate the safety of the Closed-Loop Control (CLC), also known as Artificial Pancreas (AP) named t:slim X2 with Control-IQ Technology and assess usability in a supervised setting for the treatment of type 1 diabetes (T1D) in young children (2-6 years old).

• Tandem t:slim X2 with Control-IQ Technology + Dexcom G6 (Device), also known as Artificial Pancreas, Automated Insulin Delivery Device: Subjects will use the Tandem t:slim X2 with Control- IQ Technology and Dexcom G6 CGM to control their glycemia. The Tandem t:slim X2 with Control-IQ device is an automated insulin delivery pump that automatically adjusts insulin delivery to predicted and prevailing glucose levels, as measured by a Dexcom G6 continuous glucose monitor \[CGM\].

Primary outcomes

• Primary Outcome [Baseline results are from the 2-7 day (median of 4 day) use of Open Loop before the hotel admission. AP results are from the 5 day study admission using Control IQ including 48 hours of supervised hotel admission followed by 72 hours at home.]: Percentage of subjects with less than 6% time below 70mg/dL and less than 40% time above 180mg/dL.

Secondary outcomes

• Below 70 mg/dl. [Baseline results are from the 2-7 day (median of 4 day) use of Open Loop before the hotel admission. AP results are from the 5 day study admission using Control IQ including 48 hours of supervised hotel admission followed by 72 hours at home.]: Percent of time spent below 70 mg/dl.
• Below 60 mg/dl. [Baseline results are from the 2-7 day (median of 4 day) use of Open Loop before the hotel admission. AP results are from the 5 day study admission using Control IQ including 48 hours of supervised hotel admission followed by 72 hours at home.]: Percent of time spent below 60mg/dl.
• Below 54 mg/dl. [Baseline results are from the 2-7 day (median of 4 day) use of Open Loop before the hotel admission. AP results are from the 5 day study admission using Control IQ including 48 hours of supervised hotel admission followed by 72 hours at home.]: Percent of time spent below 54mg/dL.
• Below 50mg/dl. [Baseline results are from the 2-7 day (median of 4 day) use of Open Loop before the hotel admission. AP results are from the 5 day study admission using Control IQ including 48 hours of supervised hotel admission followed by 72 hours at home.]: Percent of time spent below 50mg/dL.
• Above 180 mg/dl. [Baseline results are from the 2-7 day (median of 4 day) use of Open Loop before the hotel admission. AP results are from the 5 day study admission using Control IQ including 48 hours of supervised hotel admission followed by 72 hours at home.]: Percent of time spent above 180mg/dl.
• Above 250mg/dl. [Baseline results are from the 2-7 day (median of 4 day) use of Open Loop before the hotel admission. AP results are from the 5 day study admission using Control IQ including 48 hours of supervised hotel admission followed by 72 hours at home.]: Percent of time spent above 250mg/dl.
• Above 300 mg/dl. [Baseline results are from the 2-7 day (median of 4 day) use of Open Loop before the hotel admission. AP results are from the 5 day study admission using Control IQ including 48 hours of supervised hotel admission followed by 72 hours at home.]: Percent of time spent above 300 mg/dl.
• Between 70-140mg/dl. [Baseline results are from the 2-7 day (median of 4 day) use of Open Loop before the hotel admission. AP results are from the 5 day study admission using Control IQ including 48 hours of supervised hotel admission followed by 72 hours at home.]: Percent of time spent between 70 mg/dl and 140mg/dl.
• Between 70-180mg/dl [Baseline results are from the 2-7 day (median of 4 day) use of Open Loop before the hotel admission. AP results are from the 5 day study admission using Control IQ including 48 hours of supervised hotel admission followed by 72 hours at home.]: Percent of time spent between 70 mg/dl and 180mg/dl.
• Number of Hypoglycemia Below 70 mg/dL [Baseline results are from the 2-7 day (median of 4 day) use of Open Loop before the hotel admission. AP results are from the 5 day study admission using Control IQ including 48 hours of supervised hotel admission followed by 72 hours at home.]: Number of hypoglycemia events (below 70 mg/dL).
• Average Number of Treatments. [The 5 day period of data collection included 48 hours of supervised hotel admission. The remaining 72 hours consisted of at-home Control IQ use under parental supervision and remote study staff monitoring.]: Average number of carbohydrate treatments per day. Participants were treated with \~16g fast-acting carbohydrates for CGM readings under 80mg/dL during the day and under 70mg/dL overnight (or at higher glycemic thresholds per parent discretion). A repeat treatment was considered if CGM value was<80mg/dL after \~20min. Hypoglycemic treatments could occur at any time per study physician request
• Average of Carbohydrate Treatments (g). [The 5 day period of data collection included 48 hours of supervised hotel admission. The remaining 72 hours consisted of at-home Control IQ use under parental supervision and remote study staff monitoring.]: Average amount of carbohydrates (grams) used as a treatment. Participants were treated with \~16g fast-acting carbohydrates for CGM readings under 80mg/dL during the day and under 70mg/dL overnight (or at higher glycemic thresholds per parent discretion). A repeat treatment was considered if CGM value was<80mg/dL after \~20min. Hypoglycemic treatments could occur at any time per study physician request
• Percent of Time Spent in Closed Loop [The 5 day period of data collection included 48 hours of supervised hotel admission. The remaining 72 hours consisted of at-home Control IQ use under parental supervision and remote study staff monitoring.]: Percentage of the amount of time spent with the Control-IQ system running in closed loop mode.
• CGM Consensus Goal [Baseline results are from the 2-7 day (median of 4 day) use of Open Loop before the hotel admission. AP results are from the 5 day study admission using Control IQ including 48 hours of supervised hotel admission followed by 72 hours at home.]: Percentage of subjects with more than 70% time in 70-180mg/dL range with less than 4% time below 70mg/dL.

Sex: All, ages: 2 Years to 6 Years

Inclusion Criteria:

1. Age ≥ 2 and < 6 years old at the time of consent
2. Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least 3 months and using insulin at the time of enrollment
3. Use of an insulin pump in the past 3 months
4. Use of Dexcom G6 for at least 11 out of the last 14 days
5. Parent/guardian(s) have familiarity with and use of carbohydrate ratios for meal boluses
6. Living with one or more parent/guardian knowledgeable about emergency procedures for severe hypoglycemia and able to contact emergency services and study staff
7. At least one parent/guardian is willing to stay with the child during the hotel/house portion of the study on the dates selected by the study team
8. Investigator has confidence that the parent/guardian(s) 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 already, and to use no other insulin besides lispro (Humalog) or aspart (Novolog) during the study
10. Total daily insulin dose (TDD) of at least 5 U/day
11. Willingness not to start any new non-insulin glucose-lowering agent during the course of the trial
12. Child participant and parent/guardian(s) willingness to participate in all training sessions as directed by study staff
13. Willingness to discontinue non-Tandem t:slim insulin pumps during the entire study
14. Willingness to wear a Dexcom G6 sensor during the entire study
15. An understanding and willingness to follow the protocol and sign informed consent

Exclusion Criteria:

1. Hypoglycemia induced seizure or loss of consciousness in the past 3 months
2. Diabetes Ketoacidosis in the past 3 months
3. Use of diluted insulin
4. Concurrent use of any non-insulin glucose-lowering agent
5. Hemophilia or any other bleeding disorder
6. A condition, which in the opinion of the investigator or designee, would put the participant or study at risk. These conditions may include:

   * Acute illness at the time of the enrollment visit (fever of 101 or higher, vomiting, diarrhea)
   * Addison's disease
   * Diagnosed at less than 1 year of age without positive antibodies
   * Decreased renal function
   * Cystic fibrosis
   * Other chronic conditions, such as an underlying seizure disorder
7. Participation in another pharmaceutical or device trial at the time of enrollment or during the study.
8. Having a family member(s) 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.

Participant flow

Outcome results

• Primary Outcome (Primary), Number, percentage of subjects: Artificial Pancreas Therapy 33
• Below 70 mg/dl. (Secondary), Mean, percentage of time: Artificial Pancreas Therapy 3.7 (1.5 to 6.4)
• Below 60 mg/dl. (Secondary), Mean, percentage of time: Artificial Pancreas Therapy 1.6 (0.3 to 2.8)
• Below 54 mg/dl. (Secondary), Mean, percentage of time: Artificial Pancreas Therapy 0.6 (0.1 to 1.6)
• Below 50mg/dl. (Secondary), Mean, percentage of time: Artificial Pancreas Therapy 0.2 (0.0 to 0.9)
• Above 180 mg/dl. (Secondary), Mean, percentage of time: Artificial Pancreas Therapy 34.1 +/- 17.3
• Above 250mg/dl. (Secondary), Mean, percentage of time: Artificial Pancreas Therapy 9.7 (6.1 to 19.5)
• Above 300 mg/dl. (Secondary), Mean, percentage of time: Artificial Pancreas Therapy 3.4 (0.6 to 5.4)
• Between 70-140mg/dl. (Secondary), Mean, percentage of time: Artificial Pancreas Therapy 41.8 +/- 15.9
• Between 70-180mg/dl (Secondary), Mean, percentage of time: Artificial Pancreas Therapy 61.7 +/- 16.1
• Number of Hypoglycemia Below 70 mg/dL (Secondary), Mean, hypoglycemia event: Artificial Pancreas Therapy 2.13 +/- 1.36
• Average Number of Treatments. (Secondary), Mean, treatments/day: Artificial Pancreas Therapy 0.8 (0.3 to 1.4)
• Average of Carbohydrate Treatments (g). (Secondary), Mean, grams: Artificial Pancreas Therapy 17.5 +/- 17.6
• Percent of Time Spent in Closed Loop (Secondary), Mean, percentage of time: Artificial Pancreas Therapy 96.6 (93.6 to 98.9)
• CGM Consensus Goal (Secondary), Number, percentage of participants: Artificial Pancreas Therapy 8

Adverse events

Time frame: Up to 14 days

Limitations and caveats: Short term study in a limited number of individuals significantly limits the generalization of the results to clinical care

• Results publication: Ekhlaspour L, Schoelwer MJ, Forlenza GP, DeBoer MD, Norlander L, Hsu L, Kingman R, Boranian E, Berget C, Emory E, Buckingham BA, Breton MD, Wadwa RP. Safety and Performance of the Tandem t:slim X2 with Control-IQ Automated Insulin Delivery System in Toddlers and Preschoolers. Diabetes Technol Ther. 2021 May;23(5):384-391. doi: 10.1089/dia.2020.0507. Epub 2020 Dec 8. PMID 33226837

• Study Protocol and Statistical Analysis Plan (PDF, 2019-08-30)
• Informed Consent Form (PDF, 2019-09-27)

• Marc Breton, PhD, Principal investigator, University of Virginia Center for Diabetes Technology