학술논문
Cambridge hybrid closed-loop algorithm in children and adolescents with type 1 diabetes: a multicentre 6-month randomised controlled trial
Document Type
article
Author
Julia Ware, MD; Charlotte K Boughton, PhD; Janet M Allen, RN; Malgorzata E Wilinska, PhD; Martin Tauschmann, PhD; Louise Denvir, MD; Ajay Thankamony, MPhil; Fiona M Campbell, MD; R Paul Wadwa, ProfMD; Bruce A Buckingham, ProfMD; Nikki Davis, MD; Linda A DiMeglio, ProfMD; Nelly Mauras, MD; Rachel E J Besser, PhD; Atrayee Ghatak, MD; Stuart A Weinzimer, ProfMD; Korey K Hood, ProfPhD; D Steven Fox, MD; Lauren Kanapka, MSc; Craig Kollman, PhD; Judy Sibayan, MPH; Roy W Beck, PhD; Roman Hovorka, ProfPhD; R Hovorka; C L Acerini; A Thankamony; J M Allen; C K Boughton; K Dovc; D B Dunger; J Ware; G Musolino; M Tauschmann; M E Wilinska; J F Hayes; S Hartnell; S Slegtenhorst; Y Ruan; M Haydock; J Mangat; L Denvir; SK Kanthagnany; J Law; T Randell; P Sachdev; M Saxton; A Coupe; S Stafford; A Ball; R Keeton; R Cresswell; L Crate; H Cripps; H Fazackerley; L Looby; H Navarra; C Saddington; V Smith; V Verhoeven; S Bratt; N Khan; L Moyes; K Sandhu; C West; R P Wadwa; G Alonso; G Forlenza; R Slover; L Towers; C Berget; A Coakley; E Escobar; E Jost; S Lange; L Messer; K Thivener; F M Campbell; J Yong; E Metcalfe; M Allen; S Ambler; S Waheed; J Exall; J Tulip; B A Buckingham; L Ekhlaspour; D Maahs; L Norlander; T Jacobson; M Twon; C Weir; B Leverenz; J Keller; N Davis; A Kumaran; N Trevelyan; H Dewar; G Price; G Crouch; R Ensom; L Haskell; LM Lueddeke; N Mauras; M Benson; K Bird; K Englert; J Permuy; K Ponthieux; J Marrero-Hernandez; L A DiMeglio; H Ismail; H Jolivette; J Sanchez; S Woerner; M Kirchner; M Mullen; M Tebbe; R EJ Besser; S Basu; R London; T Makaya; F Ryan; C Megson; J Bowen-Morris; J Haest; R Law; I Stamford; A Ghatak; M Deakin; K Phelan; K Thornborough; J Shakeshaft; S A Weinzimer; E Cengiz; J L Sherr; M Van Name; K Weyman; L Carria; A Steffen; M Zgorski; J Sibayan; R W Beck; S Borgman; J Davis; J Rusnak; A Hellman; P Cheng; L Kanapka; C Kollman; C McCarthy; S Chalasani; K K Hood; S Hanes; J Viana; M Lanning; D S Fox; G Arreaza-Rubin; T Eggerman; N Green; R Janicek; D Gabrielson; S H Belle; J Castle; J Green; L Legault; S M Willi; C Wysham
Source
The Lancet: Digital Health, Vol 4, Iss 4, Pp e245-e255 (2022)
Subject
Language
English
ISSN
2589-7500
Abstract
Summary: Background: Closed-loop insulin delivery systems have the potential to address suboptimal glucose control in children and adolescents with type 1 diabetes. We compared safety and efficacy of the Cambridge hybrid closed-loop algorithm with usual care over 6 months in this population. Methods: In a multicentre, multinational, parallel randomised controlled trial, participants aged 6–18 years using insulin pump therapy were recruited at seven UK and five US paediatric diabetes centres. Key inclusion criteria were diagnosis of type 1 diabetes for at least 12 months, insulin pump therapy for at least 3 months, and screening HbA1c levels between 53 and 86 mmol/mol (7·0–10·0%). Using block randomisation and central randomisation software, we randomly assigned participants to either closed-loop insulin delivery (closed-loop group) or to usual care with insulin pump therapy (control group) for 6 months. Randomisation was stratified at each centre by local baseline HbA1c. The Cambridge closed-loop algorithm running on a smartphone was used with either (1) a modified Medtronic 640G pump, Medtronic Guardian 3 sensor, and Medtronic prototype phone enclosure (FlorenceM configuration), or (2) a Sooil Dana RS pump and Dexcom G6 sensor (CamAPS FX configuration). The primary endpoint was change in HbA1c at 6 months combining data from both configurations. The primary analysis was done in all randomised patients (intention to treat). Trial registration ClinicalTrials.gov, NCT02925299. Findings: Of 147 people initially screened, 133 participants (mean age 13·0 years [SD 2·8]; 57% female, 43% male) were randomly assigned to either the closed-loop group (n=65) or the control group (n=68). Mean baseline HbA1c was 8·2% (SD 0·7) in the closed-loop group and 8·3% (0·7) in the control group. At 6 months, HbA1c was lower in the closed-loop group than in the control group (between-group difference −3·5 mmol/mol (95% CI −6·5 to −0·5 [–0·32 percentage points, −0·59 to −0·04]; p=0·023). Closed-loop usage was low with FlorenceM due to failing phone enclosures (median 40% [IQR 26–53]), but consistently high with CamAPS FX (93% [88–96]), impacting efficacy. A total of 155 adverse events occurred after randomisation (67 in the closed-loop group, 88 in the control group), including seven severe hypoglycaemia events (four in the closed-loop group, three in the control group), two diabetic ketoacidosis events (both in the closed-loop group), and two non-treatment-related serious adverse events. There were 23 reportable hyperglycaemia events (11 in the closed-loop group, 12 in the control group), which did not meet criteria for diabetic ketoacidosis. Interpretation: The Cambridge hybrid closed-loop algorithm had an acceptable safety profile, and improved glycaemic control in children and adolescents with type 1 diabetes. To ensure optimal efficacy of the closed-loop system, usage needs to be consistently high, as demonstrated with CamAPS FX. Funding: National Institute of Diabetes and Digestive and Kidney Diseases.