Results of a noninferiority trial comparing closed-loop delivery versus delivery via an open-loop system suggest use of a closed-loop system was noninferior for pediatric patients aged 6-12 years with type 1 diabetes.
This article was originally published on AJMC.com.
Use of a closed-loop system for delivery of insulin in pediatric patients aged 6-12 years with type 1 diabetes (T1D) was shown to be safe and effective in a recent noninferiority trial.
Led by a team of investigators based in France, the study investigated outcomes among children receiving care at a Pediatric Endocrinology Department at 1 of 3 university hospitals in France and Belgium, comparing the effectiveness of insulin delivery via closed-loop and open-loop (sensor-augmented pump) systems. It was a multicenter, open-label, randomized (1:1), controlled, noninferiority, 2-session crossover trial with 21 participants that took place between May 6 and December 23, 2019, and the primary outcome was mean (SD) time spent in hypoglycemia (3.9 mmol/L [<70 mg/dL]). Ten patients started with a closed-loop system before transitioning to an open-loop system, and 11 started on an open-loop system. A 1-week washout period preceded the transition to the second system.
They used the Diabeloop DBL4K (Diabeloop, Grenoble, France) hybrid closed-loop system for their study; their inclusion criteria were diabetes for at least 1 year, maximum glycated hemoglobin (A1C) of 9% (< 75 mmol/mol), needing 8 units or more of insulin each day, and at least 3 months of insulin pump use; and the study comprised 2 phases, 72 hours of in-patient monitoring/treatment followed by 6 weeks of home monitoring.
No severe adverse outcomes occurred in either patient cohort, including severe ketoacidosis, severe hypoglycemic events, or patient death. However, 25 adverse events did occur, with 18 from the closed-loop system (8 mild, 7 moderate, 3 severe), and 7 with the open-loop system (5 mild, 2 moderate). Safety outcomes included time spent with sensor glucose concentrations less than 3.0 mmol/L and less than 3.3 mmol/L and participants who had severe hypoglycemia.
In addition, proportion of hypoglycemia duration was almost 3.5 times longer in the open-loop system than it was in the closed-loop system, for both patient cohorts (noninferiority 1-sided P < .0001):
“Time-in-range goals are rarely met in children with type 1 diabetes, except at the cost of increased hypoglycaemia episodes,” the authors wrote. “Intensive diabetes treatment benefits all patients with T1D but is even more crucial before 10 years of age, when poor glycemic control markedly increases the cardiovascular risk and can adversely affect brain and cognitive skills development.”
Their study was the first to investigate use of the Diabeloop system in a pediatric population; its safety and efficacy have only been evaluated in adults prior to this study.
The study also found the following during the in-hospital and home study phases, respectively, for the coefficient of variation of glucose:
Mean time spent with glycemia above 13.9 mmol/L (> 250 mg/dL) or 16.7 mmol/L (> 300 mg/dL) did not differ significantly between the closed- and open-loop groups for the in-hospital period. However, during the home portion of the study, the closed-loop system did lead to significantly less time with glycemia below both 3.9 mmol/L and 3.0 mmol/L, as well as time spent with glycemia above 13.9 mmol/L or 16.7 mmol/L. Further, less time was spent in a hypoglycemic state via the closed-loop system during both study phases.
Results from the Diabetes Technology Questionnaire, which evaluated participant/parent opinion, showed an overall favorable view of the closed-loop device that did not change from baseline to study conclusion, with 50% of participants expressing wanting to switch to the closed-loop system and 67% of that group actually making the switch.
Because of their small study population, the investigators noted that future studies will need to employ a larger-scale and longer-term follow-up “to assess that the glycemic control improvement remains after a 6-week period.”
This study, "Hybrid closed-loop insulin delivery versus sensor-augmented pump therapy in children aged 6–12 years: a randomised, controlled, cross-over, non-inferiority trial," was published in Lancet: Digital Health.