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Assessing the efficacy, safety and utility of closed-loop insulin delivery compared with sensor-augmented pump therapy in very young children with type 1 diabetes (KidsAP02 study): an open-label, multicentre, multinational, randomised cross-over study protocol
  1. Julia Fuchs1,2,
  2. Janet M Allen1,
  3. Charlotte K Boughton1,
  4. Malgorzata E Wilinska1,
  5. Ajay Thankamony2,
  6. Carine de Beaufort3,
  7. Fiona Campbell4,
  8. James Yong4,
  9. Elke Froehlich-Reiterer5,
  10. Julia K Mader6,
  11. Sabine E Hofer7,
  12. Thomas M Kapellen8,
  13. Birgit Rami-Merhar9,
  14. Martin Tauschmann9,
  15. Korey Hood10,
  16. Barbara Kimbell11,
  17. Julia Lawton11,
  18. Stephane Roze12,
  19. Judy Sibayan13,
  20. Nathan Cohen13,
  21. Roman Hovorka1,2
  22. on behalf of the KidsAP Consortium
    1. 1Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, University of Cambridge School of Clinical Medicine, Cambridge, UK
    2. 2Department of Paediatrics, University of Cambridge School of Clinical Medicine, Cambridge, UK
    3. 3DECCP, Clinique Pédiatrique, Centre Hospitalier de Luxembourg, Luxembourg City, Luxembourg
    4. 4Leeds Children’s Hospital, Leeds, West Yorkshire, UK
    5. 5Department of Pediatric and Adolescent Medicine, Medical University of Graz, Graz, Steiermark, Austria
    6. 6Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Steiermark, Austria
    7. 7Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Tirol, Austria
    8. 8Hospital for Children and Adolescents, University of Leipzig Faculty of Medicine, Leipzig, Sachsen, Germany
    9. 9Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Wien, Austria
    10. 10Endocrinology, Stanford University School of Medicine, Stanford, California, USA
    11. 11The University of Edinburgh Usher Institute of Population Health Sciences and Informatics, Edinburgh, Edinburgh, UK
    12. 12Vyoo Agency Sarl, Lyon, France
    13. 13Jaeb Centre for Health Research, Tampa, Florida, USA
    1. Correspondence to Professor Roman Hovorka; rh347{at}cam.ac.uk

    Abstract

    Introduction Diabetes management in very young children remains challenging. Glycaemic targets are achieved at the expense of high parental diabetes management burden and frequent hypoglycaemia, impacting quality of life for the whole family. Our objective is to assess whether automated insulin delivery can improve glycaemic control and alleviate the burden of diabetes management in this particular age group.

    Methods and analysis The study adopts an open-label, multinational, multicentre, randomised, crossover design and aims to randomise 72 children aged 1–7 years with type 1 diabetes on insulin pump therapy. Following screening, participants will receive training on study insulin pump and study continuous glucose monitoring devices. Participants will be randomised to 16-week use of the hybrid closed-loop system (intervention period) or to 16-week use of sensor-augmented pump therapy (control period) with 1–4 weeks washout period before crossing over to the other arm. The order of the two study periods will be random. The primary endpoint is the between-group difference in time spent in the target glucose range from 3.9 to 10.0 mmol/L based on sensor glucose readings during the 16-week study periods. Analyses will be conducted on an intention-to-treat basis. Key secondary endpoints are between group differences in time spent above and below target glucose range, glycated haemoglobin and average sensor glucose. Participants’ and caregivers’ experiences will be evaluated using questionnaires and qualitative interviews, and sleep quality will be assessed. A health economic analysis will be performed.

    Ethics and dissemination Ethics approval has been obtained from Cambridge East Research Ethics Committee (UK), Ethics Committees of the University of Innsbruck, the University of Vienna and the University of Graz (Austria), Ethics Committee of the Medical Faculty of the University of Leipzig (Germany) and Comité National d’Ethique de Recherche (Luxembourg). The results will be disseminated by peer-reviewed publications and conference presentations.

    Trial registration number NCT03784027.

    • general diabetes
    • paediatric endocrinology
    • paediatrics
    • diabetes & endocrinology
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    Footnotes

    • Collaborators The following are members of the KidsAP Consortium (CI - chief investigator, PI - principal investigator, I - investigator, SC - study coordinator, SN - study nurses, RA - research assistant, AM - administrative manager). Cambridge, UK: Roman Hovorka (CI and project lead), Carlo L Acerini (PI), Ajay Thankamony (PI), Charlotte K Boughton (I), Klemen Dovc (I), Julia Fuchs (I), Gianluca Musolino (I), Malgorzata E Wilinska (I), Janet M Allen (SN), Nicole Ashcroft (SC), Matthew Haydock (SC). Luxembourg: Carine de Beaufort (PI), Ulrike Schierloh (I), Muriel Fichelle (SN), Dominique Schaeffer (SN). Leeds, UK: Fiona Campbell (PI), James Yong (I), Emily Metcalfe (SN), Saima Waheed (SN), Joseph Tulip (RA). Graz, Austria: Elke Froehlich-Reiterer (PI), Maria Fritsch (I), Hildegard Jasser-Nitsche (I), Julia K Mader (I), Kerstin Faninger (SN). Innsbruck, Austria: Sabine E Hofer (PI), Daniela Abt (SN), Anita Malik (AM), Barbara Lanthaler (AM), Matthias Wenzel (AM). Leipzig, Germany: Thomas M Kapellen (PI), Heike Bartelt (I), Alena Thiele (RA). Vienna, Austria: Birgit Rami-Merhar (PI), Gabriele Berger (I), Nicole Blauensteiner (I), Renata Gellai (I), Katrin Nagl (I), Martin Tauschmann (I), Sarah Cvach (SN), Sonja Katzenbeisser-Pawlik (SN). Stanford University, CA, USA: Korey K Hood (I). Usher Institute, Edinburgh, UK: Barbara Kimbell (I), Julia Lawton (I). VYOO Agency, Lyon, France: Stephane Roze (I). Jaeb Centre for Health Research, Tampa, FL, USA: Nathan Cohen (RA), Craig Kollman (RA), Judy Sibayan (RA).

    • Contributors RH, CdB, FC, EF-R, JKM, SEH, TMK, BR-M, MT, JY, CKB, MEW, JMA, NC and AT codesigned the study. CdB, FC, EF-R, SEH, TMK, BR-M and AT are the lead clinical investigators. KH, BK and JL will conduct the psychosocial assessments. JS supported study setup. SR will conduct the cost utility analysis. RH designed and implemented the glucose controller. JF and RH wrote the manuscript. All authors critically reviewed the report. No writing assistance was provided.

    • Funding This work was supported by the European Commission within the Horizon 2020 Framework Programme under the grant agreement number 731560 and JDRF (grant number N/A). Additional support for the artificial pancreas work from National Institute for Health Research Cambridge Biomedical Research Centre (grant number N/A), and Wellcome Strategic Award (100574/Z/12/Z). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Dexcom is supplying discounted CGM devices (grant number N/A).

    • Competing interests SEH declares speaker honoraria from Eli Lilly, Pfizer and Sanofi. EF-R reports having received speaker honoraria from Minimed Medtronic and Eli Lilly, serving on advisory boards for Eli Lilly. TMK has received speaker honoraria from Minimed Medtronic, Roche and Eli Lilly and consulted Sanofi-Aventis. CdB has received speaker honoraria from Minimed Medtronic, and is member of their European Psychology Advisory Board. BR-M reports having received speaker honoraria from Abbott, Minimed Medtronic, Eli Lilly, Roche, Menarini and Novo Nordisk, serving on advisory boards for Eli Lilly. FC has received speaking fees from Abbott, Medtronic and Eli Lilly. RH reports having received speaker honoraria from Eli Lilly and Novo Nordisk, serving on advisory panel for Eli Lilly and Novo Nordisk; receiving license fees from BBraun and Medtronic; having served as a consultant to BBraun, patents and patent applications related to closed-loop insulin delivery, and director at CamDiab. JKM is shareholder of Decide Clinical Software, a member in the advisory board of Boehringer Ingelheim, Eli Lilly, Medtronic, Prediktor A/S, Roche Diabetes Care, Sanofi-Aventis and received speaker honoraria from Abbott Diabetes Care, Astra Zeneca, Dexcom, Eli Lilly, NovoNordisk A/S, Roche Diabetes Care, Servier and Takeda.

    • Patient consent for publication Not required.

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

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