PMID- 32169925 OWN - NLM STAT- MEDLINE DCOM- 20210416 LR - 20221207 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 10 IP - 3 DP - 2020 Mar 12 TI - 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. PG - e033500 LID - 10.1136/bmjopen-2019-033500 [doi] LID - e033500 AB - 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. CI - (c) Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ. FAU - Boughton, Charlotte AU - Boughton C AUID- ORCID: 0000-0003-3272-9544 AD - Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK. FAU - Allen, Janet M AU - Allen JM AD - Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK. FAU - Tauschmann, Martin AU - Tauschmann M AD - Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK. FAU - Hartnell, Sara AU - Hartnell S AD - Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK. FAU - Wilinska, Malgorzata E AU - Wilinska ME AD - Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK. FAU - Musolino, Gianluca AU - Musolino G AD - Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK. FAU - Acerini, Carlo L AU - Acerini CL AD - Department of Paediatrics, University of Cambridge, Cambridge, UK. FAU - Dunger, Professor David AU - Dunger PD AUID- ORCID: 0000-0002-2566-9304 AD - Department of Paediatrics, University of Cambridge, Cambridge, UK. FAU - Campbell, Fiona AU - Campbell F AD - Children's Diabetes Centre, Leeds Children's Hospital, Leeds, UK. FAU - Ghatak, Atrayee AU - Ghatak A AD - Department of Diabetes, Alder Hey Children's NHS Foundation Trust, Liverpool, UK. FAU - Randell, Tabitha AU - Randell T AD - Department of Paediatric Diabetes and Endocrinology, Nottingham Children's Hospital, Nottingham, UK. FAU - Besser, Rachel AU - Besser R AD - NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK. AD - Department of Paediatrics, University of Oxford, Oxford, UK. FAU - Trevelyan, Nicola AU - Trevelyan N AD - Paediatric Diabetes, Southampton Children's Hospital, Southampton, UK. FAU - Elleri, Daniela AU - Elleri D AD - Department of Diabetes, Royal Hospital for Sick Children, Edinburgh, UK. FAU - Northam, Elizabeth AU - Northam E AD - Murdoch Children's Research Institute, Parkville, Victoria, Australia. FAU - Hood, Korey AU - Hood K AD - Endocrinology, Stanford University School of Medicine, Stanford, California, USA. FAU - Scott, Eleanor AU - Scott E AD - Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK. FAU - Lawton, Julia AU - Lawton J AD - The University of Edinburgh Usher Institute of Population Health Sciences and Informatics, Edinburgh, UK. FAU - Roze, Stephane AU - Roze S AD - HEVA HEOR Sarl, Lyon, France. FAU - Sibayan, Judy AU - Sibayan J AD - Jaeb Center for Health Research, Tampa, Florida, USA. FAU - Kollman, Craig AU - Kollman C AD - Jaeb Center for Health Research, Tampa, Florida, USA. FAU - Cohen, Nate AU - Cohen N AD - Jaeb Center for Health Research, Tampa, Florida, USA. FAU - Todd, John AU - Todd J AD - Wellcome Trust Centre for Human Genetics, Oxford, UK. FAU - Hovorka, Roman AU - Hovorka R AD - Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK rh347@cam.ac.uk. CN - CLOuD Consortium LA - eng SI - ClinicalTrials.gov/NCT02871089 GR - 100574/Z/12/Z/WT_/Wellcome Trust/United Kingdom GR - 107212/A/15/Z/WT_/Wellcome Trust/United Kingdom PT - Clinical Trial Protocol PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200312 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - 0 (Glycated Hemoglobin A) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) SB - IM MH - Adolescent MH - Blood Glucose Self-Monitoring MH - Child MH - *Diabetes Mellitus, Type 1/drug therapy MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/administration & dosage/*therapeutic use MH - Insulin/administration & dosage/*therapeutic use MH - Insulin Infusion Systems MH - Insulin-Secreting Cells/drug effects/*physiology MH - Multicenter Studies as Topic MH - Randomized Controlled Trials as Topic MH - Treatment Outcome PMC - PMC7069267 OTO - NOTNLM OT - artificial pancreas OT - closed-loop OT - type 1 diabetes COIS- 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. EDAT- 2020/03/15 06:00 MHDA- 2021/04/17 06:00 PMCR- 2020/03/12 CRDT- 2020/03/15 06:00 PHST- 2020/03/15 06:00 [entrez] PHST- 2020/03/15 06:00 [pubmed] PHST- 2021/04/17 06:00 [medline] PHST- 2020/03/12 00:00 [pmc-release] AID - bmjopen-2019-033500 [pii] AID - 10.1136/bmjopen-2019-033500 [doi] PST - epublish SO - BMJ Open. 2020 Mar 12;10(3):e033500. doi: 10.1136/bmjopen-2019-033500.