Hybrid closed-loop insulin delivery versus sensor-augmented pump therapy in children aged 6-12 years: a randomised, controlled, cross-over, non-inferiority trial

Abstract

Background: Time in range (TIR) goals are rarely met in children with type 1 diabetes, except at the cost of increased hypoglycaemia episodes. Our objective was to evaluate the safety and efficiency of the Diabeloop DBL4K (Diabeloop, Grenoble, France) hybrid closed-loop system in prepubescent children.

Methods: We did a multicentre, open-label, randomised, controlled, non-inferiority, two-session crossover study in the paediatric endocrinology departments of three university hospitals in France and Belgium. Eligible participants were aged 6-12 years with type 1 diabetes for at least 1 year, glycated haemoglobin A1C 9% (75 mmol/mol) or less, and insulin pump treatment for at least 3 months. Participants were randomly assigned (1:1) to a closed-loop device or sensor-augmented pump (open loop) therapy. Randomisation was by a permuted block randomisation scheme, using an interactive web-based response system, and was stratified on centre (block size 6). The assessed closed-loop device, the Diabeloop for Kids DBL4K hybrid closed-loop system, is an automated blood glucose regulation system composed of a handset, insulin pump, and continuous glucose monitor. The open-loop system is defined as a sensor-augmented pump therapy composed of the usual insulin pump used by the patient and a continuous glucose monitor. A 72-h in-patient period was followed by a 6-week home phase. After a 1-week washout period, the participants crossed over to the other device. The primary outcome, assessed in the intention-to-treat population, was the mean proportion of time spent in hypoglycaemia (3·9 mmol/L [<70 mg/dL]) during the hospital phase, with a non-inferiority margin of -2·5% (absolute value). Safety was assessed in the intention-to-treat population on a per-protocol basis. This study was registered with ClinicalTrials.gov, NCT03671915.

Findings: Between May 6 and Dec 23, 2019, we included 21 participants (closed loop then open loop, n=10; open loop then closed loop, n=11). The proportion of time spent in hypoglycaemia was significantly lower with the closed-loop system than the open-loop system in both groups (2·04% [95% CI 0·44 to 3·64] vs 7·06% [5·46 to 8·66]; non-inferiority one-sided p<0·0001). No severe ketoacidosis, nor severe hyoglycaemic events or fatal adverse events occurred. All 25 adverse events (18 with the closed-loop system, seven with the open-loop system) were related to the treatment.

Interpretation: The closed-loop Diabeloop system decreased hypoglycaemic episodes and provided good metabolic control in prepubescent children with type 1 diabetes, under real-life conditions. This finding supports the safe use of closed-loop technology in this paediatric population.

Funding: Diabeloop.

Translation: For the French translation of the abstract see Supplementary Materials section.

Conflict of interest statement

Declaration of interests SF is a consultant for Diabeloop, a member of the scientific board of Diabeloop, a shareholder of Diabeloop, and she received speaker honoraria from Abbott, participated on a data safety monitoring board or advisory board for Novo Nordisk, and has received congress invitations from Sanofi, MSD, Roche, and Abbott. GC owns shares in Diabeloop and is chief medical officer of the Diabeloop company. P-YB has received speaker honoraria from Abbott, Eli Lilly, Novo Nordisk, Roche, and has served on advisory board panels for Abbott, Dexcom, Diabeloop, Insulet, Eli Lilly, Novo Nordisk, and Roche. EH owns shares in Diabeloop, which participated in the funding and provision of study materials, and has a leadership role in Diabeloop. KC received support for attending a meeting with Sandoz, participated on an advisory board for Abbott, and received consulting fees from Novo Nordisk. All other authors declare no competing interests.

Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.