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
Affiliations
- Julia Ware, MD
- Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK; Department of Paediatrics, University of Cambridge, Cambridge, UK
- Charlotte K Boughton, PhD
- Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK; Department of Diabetes & Endocrinology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
- Janet M Allen, RN
- Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK
- Malgorzata E Wilinska, PhD
- Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK; Department of Paediatrics, University of Cambridge, Cambridge, UK
- Martin Tauschmann, PhD
- Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK; Department of Paediatrics, University of Cambridge, Cambridge, UK
- Louise Denvir, MD
- Department of Paediatric Diabetes and Endocrinology, Nottingham University Hospitals NHS Trust, Nottingham, UK
- Ajay Thankamony, MPhil
- Department of Paediatrics, University of Cambridge, Cambridge, UK
- Fiona M Campbell, MD
- Department of Paediatric Diabetes, Leeds Children's Hospital, Leeds, UK
- R Paul Wadwa, ProfMD
- Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
- Bruce A Buckingham, ProfMD
- Division of Pediatric Endocrinology, Stanford University, Stanford, CA, USA
- Nikki Davis, MD
- Department of Paediatric Endocrinology and Diabetes, Southampton Children's Hospital, Southampton General Hospital, Southampton, UK
- Linda A DiMeglio, ProfMD
- Department of Pediatrics, Division of Pediatric Endocrinology and Diabetology, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA
- Nelly Mauras, MD
- Division of Endocrinology, Diabetes & Metabolism, Nemours Children's Health System, Jacksonville, FL, USA
- Rachel E J Besser, PhD
- Oxford University Hospitals NHS Foundation Trust, NIHR Oxford Biomedical Research Centre, Oxford, UK; Department of Paediatrics, University of Oxford, Oxford, UK
- Atrayee Ghatak, MD
- Alder Hey Children's Hospital, Liverpool, UK
- Stuart A Weinzimer, ProfMD
- Department of Pediatrics, Yale University, New Haven, CT, USA
- Korey K Hood, ProfPhD
- Division of Pediatric Endocrinology, Stanford University, Stanford, CA, USA
- D Steven Fox, MD
- Department of Pharmaceutical and Health Economics, School of Pharmacy, University of Southern California, Los Angeles, CA, USA
- Lauren Kanapka, MSc
- The Jaeb Center for Health Research, Tampa, FL, USA
- Craig Kollman, PhD
- The Jaeb Center for Health Research, Tampa, FL, USA
- Judy Sibayan, MPH
- The Jaeb Center for Health Research, Tampa, FL, USA
- Roy W Beck, PhD
- The Jaeb Center for Health Research, Tampa, FL, USA
- Roman Hovorka, ProfPhD
- Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK; Department of Paediatrics, University of Cambridge, Cambridge, UK; Correspondence: Prof Roman Hovorka, University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK
- 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
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.
