Hybrid Closed-Loop Control With Smart Prandial Insulin Dosing in Type 1 Diabetes

Type 1 Diabetes Clinical Trial

Official title:

Hybrid Closed-Loop Control With Prandial Insulin Dosing Informed by Insulin Sensitivity in Adolescents With Type 1 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04878120
• Other study ID #: 210112
• Secondary ID: 4-CDA-2020-948-A
• Status: Completed
• Phase: N/A
• Start date: May 14, 2021
• Est. completion date: June 28, 2022

Study information

• Verified date: May 2024
• Source: University of Virginia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this study is to evaluate the safety and feasibility of a smart bolus calculator that adjusts insulin dosing for meals according to real-time insulin sensitivity (SI) in adolescents with type 1 diabetes (T1D) using a hybrid closed loop (HCL) system during an active week of diabetes camp.

Description:

This is a single center, double-blind, randomized, crossover trial. The study team will target enrollment of 30 adolescents (age 12 - <18 years) with T1D who currently manage their diabetes with an insulin pump and a continuous glucose monitoring (CGM) system. Participants will be randomized 1:1 to the use of the standard HCL system (USS Virginia) vs. the HCL system with the smart bolus calculator first. The trial will be held at a local camp facility and will consist of EITHER a weeklong (6 day/5 night) camp OR two long weekends (4 day/3 night) separated by a washout period of about one week.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: June 28, 2022
• Est. primary completion date: June 24, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 17 Years

Eligibility

Inclusion Criteria:

1. Age =12 and <18 years old at time of consent

2. Clinical diagnosis, based on investigator assessment, of T1D for at least one year

3. Currently using insulin for at least six months

4. Currently using an insulin pump for at least three months

5. Currently using a CGM system for at least three months

6. Having at least 75% of CGM data over the previous four weeks

7. Using insulin parameters such as carbohydrate ratio and correction factors consistently on their pump in order to dose insulin for meals or corrections

8. Access to internet and willingness to upload data during the study as needed

9. For females, not currently known to be pregnant or breastfeeding

10. A negative urine pregnancy test will be required for all females of childbearing potential

11. Willingness to suspend use of any personal CGM for the duration of the clinical trial once the study CGM is in use

12. 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

13. Total daily insulin dose (TDD) of at least 10 U/day

14. Willingness not to start any non-insulin glucose-lowering agent during the course of the trial (including metformin, GLP-1 agonists, pramlintide, DPP-4 inhibitors, biguanides, sulfonylureas and naturaceuticals)

15. Willingness to eat at least 40 grams of carbohydrates per meal

16. An understanding and willingness to follow the protocol and signed informed consent

17. Participants and parent/legal guardians will be proficient in reading and writing in English

18. Willingness to comply with COVID-19 precautions as defined by the study team

19. Having completed a COVID-19 vaccination with an FDA-approved COVID-19 vaccine at least two weeks before the first study admission, and willing to provide a copy of the COVID-19 vaccination card

Exclusion Criteria:

1. Hemoglobin A1c <5% or >10% if measured at screening or available from historical medical report performed within the last 6 months; in absence of a valid HbA1c measurement, average blood glucose estimated from CGM data to be approximately between 100 and 240 mg/dL

2. History of diabetic ketoacidosis (DKA) in the 6 months prior to enrollment

3. Severe hypoglycemia resulting in seizure or loss of consciousness in the 6 months prior to enrollment

4. Pregnancy or intent to become pregnant during the trial

5. Currently breastfeeding or planning to breastfeed

6. Currently being treated for a seizure disorder

7. Planned surgery during study duration

8. History of cardiac arrhythmia (except for benign premature atrial contractions and benign premature ventricular contractions which are permitted)

9. Treatment with any non-insulin glucose-lowering agent (metformin, GLP-1 agonists, pramlintide, DPP-4 inhibitors, SGLT-2 inhibitors, biguanides, sulfonylureas and naturaceuticals)

10. A known medical condition that in the judgment of the investigator might interfere with the completion of the protocol.

11. Use of an insulin delivery mechanism that is not downloadable by the participant or study team

12. Known contact with COVID-positive individual within 14 days of any study admission without negative follow-up COVID-19 Polymerase Chain Reaction (PCR) test performed 3-5 days after the date of exposure

13. Symptoms of COVID-19 (e.g., fever, shortness of breath, unexpected loss of taste or smell) developed within 14 days of any study admission

14. A positive COVID-19 test within 14 days of any study admission or during study admission participation

15. Not being fully vaccinated at the time of the first camp admission (according to Center for Disease Control (CDC) guidelines a person is intended to be fully vaccinated after two weeks from either the second dose of the Pfizer or Moderna vaccine, or the single dose of the Johnson & Johnson vaccine)

Related Conditions & MeSH terms

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

Intervention

Device:
• Standard HCL System
Standard HCL system (USS Virginia)
• HCL System with Smart Bolus Calculator
HCL system (USS Virginia) with smart bolus calculator informed by insulin sensitivity

Locations

Country	Name	City	State
United States	University of Virginia Center for Diabetes Technology	Charlottesville	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
University of Virginia	Juvenile Diabetes Research Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Low Blood Glucose Index (LBGI)	LBGI computed from CGM collected in the four hours following the dinner meal.; LBGI is a metric quantifying the risk for hypoglycemia (the higher the LBGI, the higher the exposure to/risk of hypoglycemia), calculated based on the following two steps: Transforming each CGM reading in the time-series of length N into a hypoglycemia risk score (rL(i), i=1,...,N) by applying the following transformation: rL(i) = 10 x (1.509 x (log(CGM(i))^1.084 - 5.381))^2, if CGM(i) <=112.5 mg/dL; rL(i) = 0, if CGM(i) >112.5 mg/dL; Averaging the risk scores rL(i), i=1,...,N.; The hypoglycemia risk score ranges from 0 for CGM readings >112.5 mg/dL (no hypoglycemia risk) to 100 for CGM readings =20 mg/dL (maximum hypoglycemia risk); consequently, LBGI can theoretically assume values between 0 and 100 as well. Clinically relevant LBGI thresholds have been defined: LBGI <2.5: low hypoglycemia risk; LBGI in 2.5-5: moderate hypoglycemia risk; LBGI >5: high hypoglycemia risk.	4 hours (dinner postprandial period); the final metric for each intervention type is obtained as the average over two consecutive camp days (days 1-2 for the first intervention; days 3-4 for the second intervention)
Secondary	Percentage of Time Spent Below 70 mg/dL	Percentage of CGM readings in hypoglycemia below 70 mg/dL	4 hour (dinner postprandial period); average over two consecutive days for each intervention type, as described for primary outcome
Secondary	Percentage of Time Spent in 70-180 mg/dL	Percentage of CGM readings in normoglycemia between 70-180 mg/dL	4 hour (dinner postprandial period); average over two consecutive days for each intervention type, as described for primary outcome
Secondary	Percentage of Time Spent Above 180 mg/dL	Percentage of CGM readings in hyperglycemia above 180 mg/dL	4 hour (dinner postprandial period); average over two consecutive days for each intervention type, as described for primary outcome
Secondary	High Blood Glucose Index (HBGI)	HBGI computed from CGM collected in the four hours following the dinner meal.; HBGI is a metric quantifying the risk for hyperglycemia (the higher the HBGI, the higher the exposure to/risk of hyperglycemia), calculated based on the following two steps: Transforming each CGM reading in the time-series of length N into a hyperglycemia risk score (rH(i), i=1,...,N) by applying the following transformation: rH(i) = 10 x (1.509 x (log(CGM(i))^1.084 - 5.381))^2, if CGM(i) >112.5 mg/dL; rH(i) = 0, if CGM(i) <=112.5 mg/dL; Averaging the risk scores rH(i), i=1,...,N.; The hyperglycemia risk score ranges from 0 for CGM readings <=112.5 mg/dL (no hyperglycemia risk) to 100 for CGM readings =600 mg/dL (maximum hyperglycemia risk); consequently, HBGI can theoretically assume values between 0 and 100 as well. Clinically relevant HBGI thresholds have been defined: HBGI <4.5: low hyperglycemia risk; HBGI in 4.5-9: moderate hyperglycemia risk; HBGI >9: high hyperglycemia risk.	4 hour (dinner postprandial period); average over two consecutive days for each intervention type, as described for primary outcome
Secondary	CGM Coefficient of Variation	CGM coefficient of variation as a measure of glucose variability	4 hour (dinner postprandial period); average over two consecutive days for each intervention type, as described for primary outcome
Secondary	Total Amount of Carbohydrate Administered as Rescue Treatments	Total amount of carbohydrate administered as rescue treatments per study protocol	4 hour (dinner postprandial period); average over two consecutive days for each intervention type, as described for primary outcome