The Lancet: Digital Health (Apr 2022)

Cambridge hybrid closed-loop algorithm in children and adolescents with type 1 diabetes: a multicentre 6-month randomised controlled trial

  • 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

Journal volume & issue
Vol. 4, no. 4
pp. e245 – e255

Abstract

Read online

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.