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

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

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04878120

Enrollment

Registered

2021-05-07

Start date

2021-05-14

Completion date

2022-06-28

Last updated

2024-05-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Type 1 Diabetes

Keywords

Insulin Sensitivity (SI), Adolescent, Insulin Pump, Continuous Glucose Monitor (CGM), Hybrid Closed Loop (HCL), Diabetes Camp

Brief 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.

Detailed 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.

Interventions

DEVICEStandard HCL System

Standard HCL system (USS Virginia)

DEVICEHCL System with Smart Bolus Calculator

HCL system (USS Virginia) with smart bolus calculator informed by insulin sensitivity

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

12 Years to 17 Years

Healthy volunteers

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)

Design outcomes

Primary

Measure	Time frame	Description
Low Blood Glucose Index (LBGI)	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)	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: 1. 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 2. 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: 1. LBGI \<2.5: low hypoglycemia risk 2. LBGI in 2.5-5: moderate hypoglycemia risk 3. LBGI \>5: high hypoglycemia risk.

Secondary

Measure	Time frame	Description
Percentage of Time Spent in 70-180 mg/dL	4 hour (dinner postprandial period); average over two consecutive days for each intervention type, as described for primary outcome	Percentage of CGM readings in normoglycemia between 70-180 mg/dL
Percentage of Time Spent Above 180 mg/dL	4 hour (dinner postprandial period); average over two consecutive days for each intervention type, as described for primary outcome	Percentage of CGM readings in hyperglycemia above 180 mg/dL
Percentage of Time Spent Below 70 mg/dL	4 hour (dinner postprandial period); average over two consecutive days for each intervention type, as described for primary outcome	Percentage of CGM readings in hypoglycemia below 70 mg/dL
CGM Coefficient of Variation	4 hour (dinner postprandial period); average over two consecutive days for each intervention type, as described for primary outcome	CGM coefficient of variation as a measure of glucose variability
Total Amount of Carbohydrate Administered as Rescue Treatments	4 hour (dinner postprandial period); average over two consecutive days for each intervention type, as described for primary outcome	Total amount of carbohydrate administered as rescue treatments per study protocol
High Blood Glucose Index (HBGI)	4 hour (dinner postprandial period); average over two consecutive days for each intervention type, as described for primary outcome	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: 1. 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 2. 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: 1. HBGI \<4.5: low hyperglycemia risk 2. HBGI in 4.5-9: moderate hyperglycemia risk 3. HBGI \>9: high hyperglycemia risk.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Standard HCL Control - HCL Control With Smart Bolus Calculator Use of standard HCL system followed by use of HCL system with smart bolus calculator informed by insulin sensitivity	12
HCL Control With Smart Bolus Calculator - Standard HCL Control Use of HCL system with smart bolus calculator informed by insulin sensitivity followed by use of standard HCL system	11
Total	23

Baseline characteristics

Characteristic	Standard HCL Control - HCL Control With Smart Bolus Calculator	Total	HCL Control With Smart Bolus Calculator - Standard HCL Control
Age, Categorical <=18 years	12 Participants	23 Participants	11 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	0 Participants	0 Participants	0 Participants
Age, Continuous	13.8 years STANDARD_DEVIATION 1.7	14.2 years STANDARD_DEVIATION 1.6	14.6 years STANDARD_DEVIATION 1.3
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants	23 Participants	11 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Hemoglobin A1c	7.2 % STANDARD_DEVIATION 0.4	7.2 % STANDARD_DEVIATION 0.6	7.2 % STANDARD_DEVIATION 0.8
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) More than one race	1 Participants	2 Participants	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	11 Participants	20 Participants	9 Participants
Region of Enrollment United States	12 Participants	23 Participants	11 Participants
Sex: Female, Male Female	6 Participants	11 Participants	5 Participants
Sex: Female, Male Male	6 Participants	12 Participants	6 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 25	0 / 25
other Total, other adverse events	0 / 25	2 / 25
serious Total, serious adverse events	0 / 25	0 / 25

Outcome results

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: 1. 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 2. 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: 1. LBGI \<2.5: low hypoglycemia risk 2. LBGI in 2.5-5: moderate hypoglycemia risk 3. LBGI \>5: high hypoglycemia risk.

Time frame: 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)

Arm	Measure	Group	Value (MEAN)	Dispersion
Standard HCL Control - HCL Control With Smart Bolus Calculator	Low Blood Glucose Index (LBGI)	Camp days 3-4	1.1 score on a scale	Standard Deviation 0.78
Standard HCL Control - HCL Control With Smart Bolus Calculator	Low Blood Glucose Index (LBGI)	Camp days 1-2	2.87 score on a scale	Standard Deviation 2.59
HCL Control With Smart Bolus Calculator - Standard HCL Control	Low Blood Glucose Index (LBGI)	Camp days 3-4	1.70 score on a scale	Standard Deviation 0.79
HCL Control With Smart Bolus Calculator - Standard HCL Control	Low Blood Glucose Index (LBGI)	Camp days 1-2	3.19 score on a scale	Standard Deviation 1.73

Comparison: The study followed a randomized crossover design, with two study groups and two intervention types; the two groups differed in the order they received the two intervention types. To test the hypothesis that HCL Control with Smart Bolus Calculator reduces exposure to hypoglycemia with respect to Standard HCL Control, a mixed ANOVA was performed with LBGI as outcome measure, study group as between-subject factor, and intervention type as within-subject factor.p-value: 0.733ANOVA

Secondary