Cambridge Hybrid Closed-Loop Algorithm in Children and Adolescents with Type 1 Diabetes: A Multicentre 6-Month Randomised Trial

Background: Closed-loop insulin delivery systems have the potential to address the issue of suboptimal glucose control in children and adolescents with type 1 diabetes. We compared safety and efficacy of Cambridge hybrid closed-loop algorithm with usual care over six months in this population. Methods: In a multicentre, multinational, one-period, parallel randomised controlled trial, participants aged 6-18 years using insulin pump therapy were recruited at seven UK and five US paediatric diabetes centres. We randomly assigned participants to closed-loop insulin delivery or to usual care (control) for six months. The Cambridge closed-loop algorithm running on a smartphone was used with either (i) modified Medtronic 640G pump, Medtronic Guardian 3 sensor, and Medtronic prototype phone enclosure (FlorenceM configuration) or (ii) Sooil Dana RS pump and Dexcom G6 sensor (CamAPS FX configuration). Primary endpoint was change in HbA1c at six months combing data from both configurations. Analysis was by intention-to-treat. Trial registration ClinicalTrials.gov, NCT02925299. Findings: We randomised 133 participants (mean±SD baseline HbA1c 8·2±0·7% vs 8·3±0·7%), 65 to closed-loop and 68 to control. At six months, HbA1c was 0·32% lower with closed-loop compared to control (95%CI 0·04 to 0·59; p=0·02). Closed-loop usage was low with FlorenceM due to failing phone enclosures (40% [26, 53]; median [IQR]), but consistently high with CamAPS FX (93% [88, 96]). In post-hoc analysis, HbA1c in the CamAPS FX closed-loop cohort (n=21) was 1·05% lower (95%CI 0·67 to 1·43; p