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  • Assessing the effect of closed-loop insulin delivery from onset of type 1 diabetes in youth on residual beta-cell function compared to standard insulin therapy (CLOuD study): a randomised parallel study protocol

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Diabetes and endocrinology
Protocol
Assessing the effect of closed-loop insulin delivery from onset of type 1 diabetes in youth on residual beta-cell function compared to standard insulin therapy (CLOuD study): a randomised parallel study protocol
  1. Charlotte Boughton1,
  2. Janet M Allen1,
  3. Martin Tauschmann1,
  4. Sara Hartnell1,
  5. Malgorzata E Wilinska1,
  6. Gianluca Musolino1,
  7. Carlo L Acerini2,
  8. Professor David Dunger2,
  9. Fiona Campbell3,
  10. Atrayee Ghatak4,
  11. Tabitha Randell5,
  12. Rachel Besser6,7,
  13. Nicola Trevelyan8,
  14. Daniela Elleri9,
  15. Elizabeth Northam10,
  16. Korey Hood11,
  17. Eleanor Scott12,
  18. Julia Lawton13,
  19. Stephane Roze14,
  20. Judy Sibayan15,
  21. Craig Kollman15,
  22. Nate Cohen15,
  23. John Todd16,
  24. Roman Hovorka1
  25. on behalf of CLOuD Consortium
  1. 1Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK
  2. 2Department of Paediatrics, University of Cambridge, Cambridge, UK
  3. 3Children’s Diabetes Centre, Leeds Children's Hospital, Leeds, UK
  4. 4Department of Diabetes, Alder Hey Children's NHS Foundation Trust, Liverpool, UK
  5. 5Department of Paediatric Diabetes and Endocrinology, Nottingham Children's Hospital, Nottingham, UK
  6. 6NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
  7. 7Department of Paediatrics, University of Oxford, Oxford, UK
  8. 8Paediatric Diabetes, Southampton Children's Hospital, Southampton, UK
  9. 9Department of Diabetes, Royal Hospital for Sick Children, Edinburgh, UK
  10. 10Murdoch Children’s Research Institute, Parkville, Victoria, Australia
  11. 11Endocrinology, Stanford University School of Medicine, Stanford, California, USA
  12. 12Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
  13. 13The University of Edinburgh Usher Institute of Population Health Sciences and Informatics, Edinburgh, UK
  14. 14HEVA HEOR Sarl, Lyon, France
  15. 15Jaeb Center for Health Research, Tampa, Florida, USA
  16. 16Wellcome Trust Centre for Human Genetics, Oxford, UK
  1. Correspondence to Dr Roman Hovorka; rh347{at}cam.ac.uk

Abstract

Introduction Management of newly diagnosed type 1 diabetes (T1D) in children and adolescents is challenging for patients, families and healthcare professionals. The objective of this study is to determine whether continued intensive metabolic control using hybrid closed-loop (CL) insulin delivery following diagnosis of T1D can preserve C-peptide secretion, a marker of residual beta-cell function, compared with standard multiple daily injections (MDI) therapy.

Methods and analysis The study adopts an open-label, multicentre, randomised, parallel design, and aims to randomise 96 participants aged 10–16.9 years, recruited within 21 days of diagnosis with T1D. Following a baseline mixed meal tolerance test (MMTT), participants will be randomised to receive 24 months treatment with conventional MDI therapy or with CL insulin delivery. A further 24-month optional extension phase will be offered to all participants to continue with the allocated treatment. The primary outcome is the between group difference in area under the stimulated C-peptide curve (AUC) of the MMTT at 12 months post diagnosis. Analyses will be conducted on an intention-to-treat basis. Key secondary outcomes are between group differences in time spent in target glucose range (3.9–10 mmol/L), glycated haemoglobin (HbA1c) and time spent in hypoglycaemia (<3.9 mmol/L) at 12 months. Secondary efficacy outcomes include between group differences in stimulated C-peptide AUC at 24 months, time spent in target glucose range, glucose variability, hypoglycaemia and hyperglycaemia as recorded by periodically applied masked continuous glucose monitoring devices, total, basal and bolus insulin dose, and change in body weight. Cognitive, emotional and behavioural characteristics of participants and parents will be evaluated, and a cost–utility analysis performed to support adoption of CL as a standard treatment modality following diagnosis of T1D.

Ethics and dissemination Ethics approval has been obtained from Cambridge East Research Ethics Committee. The results will be disseminated by peer-reviewed publications and conference presentations.

Trial registration number NCT02871089; Pre-results.

  • type 1 diabetes
  • closed-loop
  • artificial pancreas
https://creativecommons.org/licenses/by/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

https://doi.org/10.1136/bmjopen-2019-033500

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    Footnotes

    • Contributors RH, MEW, CLA, FC, AG, TR, RB, NT, DE and KH codesigned the study. CK and NC designed the statistical plan. CB, JMA, MT, SH, GM, CLA, DE, FC, AG, TR, RB, NT and DE screened and enrolled participants, arranged informed consent from the participants, provided patient care and took samples. KH, EN, JL and ES will conduct the psychosocial assessments. SR conducted the cost utility analysis. JT conducted the immunology assessments. JS coordinated the study. RH designed and implemented the glucose controller. CB and RH wrote the manuscript. All authors critically reviewed the report. No writing assistance was provided.

    • Funding National Institute for Health Research EME Grant (14/23/09) and Leona M & Harry B Helmsley Charitable Trust Grant (#2016PG-T1D046). Additional support for the artificial pancreas work is from National Institute for Health Research Cambridge Biomedical Research Centre, and Wellcome Strategic Award (100574/Z/12/Z). Medtronic and Dexcom are supplying discounted CGM devices, sensors and details of communication protocol to facilitate real-time connectivity. Abbott Diabetes Care is providing Libre Pro sensors. JAT is supported by a strategic award to the Diabetes and Inflammation Laboratory from the JDRF (4-SRA-2017–473-A-A) and the Wellcome Trust (107212/A/15/Z), and a grant from the JDRF (1-SRA-2019–657-A-N).

    • Competing interests RH reports having received speaker honoraria from Eli Lilly and Novo Nordisk, serving on advisory panel for Eli Lilly and Novo Nordisk, receiving licence fees from BBraun and Medtronic. RH and MEW report patient patents and patent applications. MT has received speaker honoraria from Medtronic and Novo Nordisk. SH is a member of Sigma (Dexcom) advisory board and reports having received training honoraria from Medtronic and Sanofi. TLR has received speaker honoraria from Novo Nordisk and serves as a consultant for Abbott Diabetes Care. KH has received research support from Dexcom, Inc for an investigator-initiated project; he has received consultant fees from Lilly Innovation Center, Bigfoot Biomedical, and Insulet, Inc.

    • Patient consent for publication Not required.

    • Ethics approval The study has received approval from the Cambridge East Research Ethics Committee in the UK (#16/EE/0286) and has undergone review by regulatory authorities in the UK (Medicines and Healthcare products Regulatory Agency).

    • Provenance and peer review Not commissioned; externally peer reviewed.