Trial of Hybrid Closed-Loop Control in Young Children with Type 1 Diabetes

Abstract

Background: Closed-loop control systems of insulin delivery may improve glycemic outcomes in young children with type 1 diabetes. The efficacy and safety of initiating a closed-loop system virtually are unclear.

Methods: In this 13-week, multicenter trial, we randomly assigned, in a 2:1 ratio, children who were at least 2 years of age but younger than 6 years of age who had type 1 diabetes to receive treatment with a closed-loop system of insulin delivery or standard care that included either an insulin pump or multiple daily injections of insulin plus a continuous glucose monitor. The primary outcome was the percentage of time that the glucose level was in the target range of 70 to 180 mg per deciliter, as measured by continuous glucose monitoring. Secondary outcomes included the percentage of time that the glucose level was above 250 mg per deciliter or below 70 mg per deciliter, the mean glucose level, the glycated hemoglobin level, and safety outcomes.

Results: A total of 102 children underwent randomization (68 to the closed-loop group and 34 to the standard-care group); the glycated hemoglobin levels at baseline ranged from 5.2 to 11.5%. Initiation of the closed-loop system was virtual in 55 patients (81%). The mean (±SD) percentage of time that the glucose level was within the target range increased from 56.7±18.0% at baseline to 69.3±11.1% during the 13-week follow-up period in the closed-loop group and from 54.9±14.7% to 55.9±12.6% in the standard-care group (mean adjusted difference, 12.4 percentage points [equivalent to approximately 3 hours per day]; 95% confidence interval, 9.5 to 15.3; P<0.001). We observed similar treatment effects (favoring the closed-loop system) on the percentage of time that the glucose level was above 250 mg per deciliter, on the mean glucose level, and on the glycated hemoglobin level, with no significant between-group difference in the percentage of time that the glucose level was below 70 mg per deciliter. There were two cases of severe hypoglycemia in the closed-loop group and one case in the standard-care group. One case of diabetic ketoacidosis occurred in the closed-loop group.

Conclusions: In this trial involving young children with type 1 diabetes, the glucose level was in the target range for a greater percentage of time with a closed-loop system than with standard care. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases; PEDAP ClinicalTrials.gov number, NCT04796779.).

Figure 1.. Mean Percentage of Time with the Glucose Level in the Target Range.

Panel A shows the mean percentage of time that the glucose level was in the target range of 70 to 180 mg per deciliter (3.9 to 10.0 mmol per liter) each week over the 13 weeks of the trial among patients who were assigned to receive treatment with either a closed-loop system or standard care. The inset shows the mean percentage of time that the glucose level was in the target range each day for the first 7 days in the closed-loop group, according to whether the patient had been using an insulin pump or receiving multiple daily injections of insulin before the trial. The circles denote the mean values, and the vertical lines extend to ±1 SE of the mean. Panel B shows an envelope plot of the same outcome, as measured by continuous glucose monitoring, according to the time of day over the 13-week period. The circles denote the hourly median values, and the lower and upper boundary of each shaded region the 25th and 75th percentiles, respectively.

Figure 2.. Changes from Baseline in Time within the Target Glucose Range and the Glycated Hemoglobin Level.

Panel A shows the change from baseline (randomization) to 13 weeks in the percentage of time with the glucose level in the target range of 70 to 180 mg per deciliter, according to the baseline glycated hemoglobin level. The numbers of patients in each baseline group were the following: glycated hemoglobin level less than 7.0%, 22 patients in the closed-loop group and 8 patients in the standard-care group; glycated hemoglobin level 7.0 to 7.4%, 11 and 6 patients, respectively; glycated hemoglobin level 7.5 to 8.4%, 15 and 11 patients, respectively; and glycated hemoglobin level 8.5% or higher, 15 and 7 patients, respectively. Panel B shows the change from baseline to 13 weeks in glycated hemoglobin levels, according to the baseline glycated hemoglobin level. The numbers of patients in each baseline group were the following: glycated hemoglobin level less than 7.0%, 21 patients in the closed-loop group and 8 patients in the standard-care group; glycated hemoglobin level 7.0 to 7.4%, 10 and 6 patients, respectively; glycated hemoglobin level 7.5 to 8.4%, 14 and 10 patients, respectively; and glycated hemoglobin level 8.5% or higher, 14 and 7 patients, respectively. In both panels, the black dots denote the mean values, the horizontal bars in the boxes the median values, and the lower and upper boundaries of each box the 25th and 75th percentiles, respectively.