Fully Automated Closed Loop Control in Adolescents With Type 1 Diabetes (RocketAP)

• ClinicalTrials.gov Identifier: NCT04545567
• Recruitment Status: Completed
• First Posted: September 11, 2020
• Results First Posted: March 31, 2022
• Last Update Posted: April 20, 2022
• Sponsor: University of Virginia
• Information provided by (Responsible Party): Mark D. DeBoer, MD, MSc., MCR, University of Virginia

Tracking Information

• First Submitted Date: September 3, 2020
• First Posted Date: September 11, 2020
• Results First Submitted Date: January 13, 2022
• Results First Posted Date: March 31, 2022
• Last Update Posted Date: April 20, 2022
• Actual Study Start Date: December 16, 2020
• Actual Primary Completion Date: January 18, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 7, 2022)

Percentage of Time From Dinner Time Until Midnight With Blood Glucose in Range 70-180 mg/dL in the Unannounced Meal [ Time Frame: 6 hours ]

Percentage of time from dinner time until midnight with blood glucose in range 70-180 mg/dL in the unannounced meal

Original Primary Outcome Measures (submitted: September 3, 2020)

time in range 70-180 mg/dL from dinner time until midnight [ Time Frame: 6 hours ]

time in range 70-180 mg/dL from dinner time until midnight

Current Secondary Outcome Measures (submitted: March 31, 2022)

• Number of Hypoglycemia Events From Dinner Time Until Midnight [ Time Frame: 6 hours ]
  Number of hypoglycemia events from dinner time until midnight
• Percentage of Time From Dinner Time Until Midnight With Blood Glucose in Range < 70 mg/dL [ Time Frame: 6 hours ]
  Percentage of Time From Dinner Time Until Midnight With Blood Glucose in Range < 70 mg/dL
• Percentage of Time From Dinner Time Until Midnight With Blood Glucose in Range >180 mg/dL [ Time Frame: 6 hours ]
  Percentage of Time From Dinner Time Until Midnight With Blood Glucose in Range >180 mg/dL
• Percentage of Time From Dinner Time Until Midnight With Blood Glucose in Range >250 mg/dL [ Time Frame: 6 hours ]
  Percentage of Time From Dinner Time Until Midnight With Blood Glucose in Range >250 mg/dL
• Units of Insulin Injected From Dinner Time Until Midnight [ Time Frame: 6 hours ]
  Units of insulin injected from dinner time until midnight
• The Blood Glucose Area Under the Curve (AUC) From Dinner Until Midnight, Accounting for the Initial Blood Glucose Value [ Time Frame: 6 hours ]
  The blood glucose area under the curve (AUC) from dinner until midnight, accounting for the initial blood glucose value.
• Percentage of Time From Dinner Time Until Dinner Time + 12h With Blood Glucose in Range 70-180 mg/dL [ Time Frame: 12 hours ]
  Percentage of time from dinner time until dinner time + 12h with blood glucose in range 70-180 mg/dL
• Number of Hypoglycemia Events From Dinner Time Until Dinner Time + 12h [ Time Frame: 12 hours ]
  Number of hypoglycemia events from dinner Time until dinner time + 12h
• Percentage of Time From Dinner Time Until Dinner Time + 12h With Blood Glucose in Range <70 mg/dL [ Time Frame: 12 hours ]
  Percentage of time from dinner time until dinner time + 12h with blood Glucose in range <70 mg/dL
• Percentage of Time From Dinner Time Until Dinner Time + 12h With Blood Glucose >180 mg/dL [ Time Frame: 12 hours ]
  Percentage of Time From Dinner Time Until Dinner Time + 12h With Blood Glucose >180 mg/dL
• Percentage of Time From Dinner Time Until Dinner Time + 12h With Blood Glucose >250 mg/dL [ Time Frame: 12 hours ]
  Percentage of Time From Dinner Time Until Dinner Time + 12h With Blood Glucose >250 mg/dL
• Units of Insulin Injected From Dinner Time Until Dinner Time + 12h [ Time Frame: 12 hours ]
  Units of insulin injected from dinner time until dinner time + 12h
• The Blood Glucose Area Under the Curve (AUC) From Dinner Until Dinner + 12h, Accounting for the Initial Blood Glucose Value [ Time Frame: 12 hours ]
  The Blood Glucose Area Under the Curve (AUC) From Dinner Until dinner + 12h, Accounting for the Initial Blood Glucose Value
• Percentage of Time Outside the Dinner Sessions With Blood Glucose in Range 70-180 mg/dL [ Time Frame: 36 hours ]
  Percentage of Time outside the dinner sessions With Blood Glucose in Range 70-180 mg/dL
• Number of Hypoglycemia Events Outside of the Study Dinner Sessions [ Time Frame: 36 hours ]
  Number of hypoglycemia events outside of the Study Dinner Sessions
• Percentage of Time Outside of the Study Dinner Sessions With Blood Glucose <70 mg/dL [ Time Frame: 36 hours ]
  Percentage of Time outside of the Study Dinner Sessions with Blood Glucose <70 mg/dL
• Percent of Time Outside of the Study Dinner Sessions With Blood Glucose >180 mg/dL [ Time Frame: 36 hours ]
  Percent of Time Outside of the Study Dinner Sessions with Blood Glucose >180 mg/dL
• Percent Time Outside of the Study Dinner Sessions With Blood Glucose >250 mg/dL [ Time Frame: 36 hours ]
  Percent Time Outside of the Study Dinner Sessions with Blood Glucose >250 mg/dL
• Units of Insulin Injected Outside of the Study Dinner Sessions [ Time Frame: 36 hours ]
  Units of insulin injected outside of the Study Dinner Sessions

Original Secondary Outcome Measures (submitted: September 3, 2020)

• Number of hypoglycemia events beginning after dinner and for 6h thereafter [ Time Frame: 6 hours ]
  Number of hypoglycemia events beginning after dinner and for 6h thereafter
• Time <70 mg/dL beginning after dinner and for 6h thereafter [ Time Frame: 6 hours ]
  Time <70 mg/dL beginning after dinner and for 6h thereafter
• Time >180 mg/dL beginning after dinner and for 6h thereafter [ Time Frame: 6 hours ]
  Time >180 mg/dL beginning after dinner and for 6h thereafter
• Time >250 mg/dL beginning after dinner and for 6h thereafter [ Time Frame: 6 hours ]
  Time >250 mg/dL beginning after dinner and for 6h thereafter
• Units of insulin injected beginning after dinner and for 6h thereafter [ Time Frame: 6 hours ]
  Units of insulin injected beginning after dinner and for 6h thereafter
• Area under the curve when accounting for starting BG beginning after dinner and for 6h thereafter [ Time Frame: 6 hours ]
  Area under the curve when accounting for starting BG beginning after dinner and for 6h thereafter
• Time in range 70-180 mg/dL beginning of dinner until 12 hours later [ Time Frame: 12 hours ]
  Time in range 70-180 mg/dL beginning of dinner until 12 hours later
• Number of hypoglycemia events beginning of dinner until 12 hours later [ Time Frame: 12 hours ]
  Number of hypoglycemia events beginning of dinner until 12 hours later
• Time <70 mg/dL beginning of dinner until 12 hours later [ Time Frame: 12 hours ]
  Time <70 mg/dL beginning of dinner until 12 hours later
• Time >180 mg/dLbeginning of dinner until 12 hours later [ Time Frame: 12 hours ]
  Time >180 mg/dLbeginning of dinner until 12 hours later
• Time >250 mg/dLbeginning of dinner until 12 hours later [ Time Frame: 12 hours ]
  Time >250 mg/dLbeginning of dinner until 12 hours later
• Units of insulin injected beginning of dinner until 12 hours later [ Time Frame: 12 hours ]
  Units of insulin injected beginning of dinner until 12 hours later
• Area under the curve when accounting for starting BG beginning of dinner until 12 hours later [ Time Frame: 12 hours ]
  Area under the curve when accounting for starting BG beginning of dinner until 12 hours later
• Time in range 70-180 mg/dL outside of the Study Dinner Sessions [ Time Frame: 2 days ]
  Time in range 70-180 mg/dL outside of the Study Dinner Sessions
• Number of hypoglycemia events outside of the Study Dinner Sessions [ Time Frame: 2 days ]
  Number of hypoglycemia events outside of the Study Dinner Sessions
• Time <70 mg/dL outside of the Study Dinner Sessions [ Time Frame: 2 days ]
  Time <70 mg/dL outside of the Study Dinner Sessions
• Time >180 mg/dL outside of the Study Dinner Sessions [ Time Frame: 2 days ]
  Time >180 mg/dL outside of the Study Dinner Sessions
• Time >250 mg/dLoutside of the Study Dinner Sessions [ Time Frame: 2 days ]
  Time >250 mg/dLoutside of the Study Dinner Sessions
• Units of insulin injected outside of the Study Dinner Sessions [ Time Frame: 2 days ]
  Units of insulin injected outside of the Study Dinner Sessions

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Fully Automated Closed Loop Control in Adolescents With Type 1 Diabetes
• Official Title: Fully Automated Closed Loop Control in Adolescents With Type 1 Diabetes (Rocket AP)
• Brief Summary: The study team will be comparing two investigational Artificial Pancreas (AP) systems that the UVA Center for Diabetes Technology has developed. An artificial pancreas system delivers insulin automatically based on a blood glucose level that is provided from a continuous glucose monitor (CGM).

Detailed Description

Maintaining blood glucose (BG) control among adolescents with Type 1 diabetes (T1D) is arguably the greatest challenge in the entire field of T1D. One reason for this poor control relates to missed meal boluses, which affects 65% of adolescents at least once weekly, with 38% missing at least 15% of their boluses. Adolescents who miss four boluses weekly experience an increase of 1% in their HbA1c. While the advent of the artificial pancreas (AP) offers promise of safe reductions in HbA1c, the study team previously found that the AP only partly compensates for missed prandial insulin -demonstrating that some form of meal announcement is necessary for good BG control, even with an AP. One way to automate this process is by sharing the prandial dosing responsibilities between an automated insulin priming (based on continuous glucose monitor condition predictive of a safe situation for such insulin dosing) and a closed loop controller capable of reconstructing (estimating) the prevailing glucose rate of appearance from an unannounced meal. The study team has developed such an insulin priming schema and integrated it into a new version of the robust Model Predictive Controller University of Virginia AP system (called the RocketAP).

In the current study, the investigators are testing this new AP system in two configurations: hybrid and fully automated, among up to 20 adolescents. The primary outcome will be one of efficacy in assessing how well the new system controls post-prandial BG in the absence of carbohydrate (CHO) announcement as compared to the same situation but using the Control-IQ closed loop algorithm, also designed at UVa and using the same modular architecture and safety system, but without insulin priming and with a less advanced model-based controller. Further comparisons will be made to BG control on RocketAP with CHO announcement and on Control-IQ with CHO announcement. Adolescents will be started on the respective University of Virginia AP systems (RocketAP and Control-IQ in random order, both implemented on the DiAs platform, MAF 2109) and followed over the course of two dinners on each of the two platforms: a dinner where CHO is announced as normal and the 2nd where no announcement is made.

The study team hypothesize that performances of RocketAP in fully automated mode will lie in between Hybrid and Fully Automated Control-IQ. In time, this may provide an opportunity to improve BG control among adolescents who miss meal announcement.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:

A randomized cross-over trial assessing glycemic responses to two different approaches to insulin dosing for carbohydrate ingestion (announced vs. unannounced), with two different AP systems (RocketAP vs. USS Virginia, aka Control-IQ, in random order)

Masking: None (Open Label)
Primary Purpose: Other

• Condition: Type 1 Diabetes

Intervention

• Device: RocketAP
  Artificial pancreas system which is designed to be able to identify when you have eaten and provide insulin for this meal
• Device: USS Virginia
  Artificial pancreas system which responds to glucose fluctuations by modulating insulin delivery but does not specifically detect meal ingestion

Study Arms

• Experimental: RocketAP
  Adolescents will be assessed for a 48-70 hour period on the Rocket AP. This time will include two dinner times, one with and one without announcement of carbohydrate content. This is a cross-over study, so all participants will also be tested on the USS Virginia system under the same conditions.
  Intervention: Device: RocketAP
• Active Comparator: USS Virginia
  Adolescents will be assessed for a 48-70 hour period on the USS Virginia system. This time will include two dinner times, one with and one without announcement of carbohydrate content. This is a cross-over study, so all participants will also be tested on the Rocket AP system under the same conditions.
  Intervention: Device: USS Virginia

• Publications *: Garcia-Tirado J, Diaz JL, Esquivel-Zuniga R, Koravi CLK, Corbett JP, Dawson M, Wakeman C, Barnett CL, Oliveri MC, Myers H, Krauthause K, Breton MD, DeBoer MD. Advanced Closed-Loop Control System Improves Postprandial Glycemic Control Compared With a Hybrid Closed-Loop System Following Unannounced Meal. Diabetes Care. 2021 Aug 15:dc210932. doi: 10.2337/dc21-0932. Online ahead of print.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 13, 2022): 21
• Original Estimated Enrollment (submitted: September 3, 2020): 30
• Actual Study Completion Date: January 21, 2021
• Actual Primary Completion Date: January 18, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Age ≥12.0 and ≤25 years old at time of consent
2. Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least one year
3. Currently using insulin for at least six months
4. Currently using insulin pump for at least three months
5. Using insulin parameters such as carbohydrate ratio and correction factors consistently on their pump in order to dose insulin for meals or corrections
6. Access to internet and willingness to upload data during the study as needed
7. For females, not currently known to be pregnant or breastfeeding
8. 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 childbearing 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.
9. Willingness to suspend use of any personal CGM for the duration of the clinical trial once the study CGM is in use
10. Willingness to use the UVa artificial pancreas system throughout study sessions.
11. 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
12. Total daily insulin dose (TDD) at least 10 U/day and not more than 100 U/d
13. Willingness not to start any new non-insulin glucose-lowering agent during the course of the trial (including metformin, GLP-1 agonists, pramlintide, DPP-4 inhibitors, biguanides, sulfonylureas and naturaceuticals)
14. Willingness to eat at least 1 g/kg of carbohydrate per day during the camp/hotel admission
15. Willingness to reschedule Study Dinner Sessions if placed on oral steroids
16. An understanding and willingness to follow the protocol and signed informed consent

Exclusion Criteria:

1. History of diabetic ketoacidosis (DKA) in the 12 months prior to enrollment
2. Severe hypoglycemia resulting in seizure or loss of consciousness in the 12 months prior to enrollment
3. Pregnancy or intent to become pregnant during the trial
4. Currently being treated for a seizure disorder
5. Planned surgery during study duration
6. Treatment with any non-insulin glucose-lowering agent (including metformin, GLP-1 agonists, pramlintide, DPP-4 inhibitors, SGLT-2 inhibitors, biguanides, sulfonylureas and naturaceuticals)
7. A known medical condition that in the judgment of the investigator might interfere with the completion of the protocol.
8. Use of an automated insulin delivery mechanism that is not downloadable by the subject or study team

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years to 25 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04545567
• Other Study ID Numbers: 200235
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Pending
• Supporting Materials: Study Protocol
• Supporting Materials: Informed Consent Form (ICF)
• Time Frame: Generally will be available after publications completed.
• Access Criteria: No restrictions for access.

• Current Responsible Party: Mark D. DeBoer, MD, MSc., MCR, University of Virginia
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Virginia
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Mark D DeBoer, MD, MSc, MCR; University of Virginia Center for Diabetes Technology

• PRS Account: University of Virginia
• Verification Date: March 2022