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

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 fo...

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Main Authors: Fiona Campbell, John Todd, Tabitha Randell, Daniela Elleri, Gianluca Musolino, Janet M Allen, Sara Hartnell, Malgorzata E Wilinska, Martin Tauschmann, Charlotte Boughton, Nicola Trevelyan, Carlo L Acerini, Korey Hood, Craig Kollman, Judy Sibayan, Roman Hovorka, Professor David Dunger, Atrayee Ghatak, Rachel Besser, Elizabeth Northam, Eleanor Scott, Julia Lawton, Stephane Roze, Nate Cohen
Format: Article
Language:English
Published: BMJ Publishing Group 2020-03-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/10/3/e033500.full
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author Fiona Campbell
John Todd
Tabitha Randell
Daniela Elleri
Gianluca Musolino
Janet M Allen
Sara Hartnell
Malgorzata E Wilinska
Martin Tauschmann
Charlotte Boughton
Nicola Trevelyan
Carlo L Acerini
Korey Hood
Craig Kollman
Judy Sibayan
Roman Hovorka
Professor David Dunger
Atrayee Ghatak
Rachel Besser
Elizabeth Northam
Eleanor Scott
Julia Lawton
Stephane Roze
Nate Cohen
author_facet Fiona Campbell
John Todd
Tabitha Randell
Daniela Elleri
Gianluca Musolino
Janet M Allen
Sara Hartnell
Malgorzata E Wilinska
Martin Tauschmann
Charlotte Boughton
Nicola Trevelyan
Carlo L Acerini
Korey Hood
Craig Kollman
Judy Sibayan
Roman Hovorka
Professor David Dunger
Atrayee Ghatak
Rachel Besser
Elizabeth Northam
Eleanor Scott
Julia Lawton
Stephane Roze
Nate Cohen
author_sort Fiona Campbell
collection DOAJ
description 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.
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spelling doaj-art-b051c1ecba6d43e7bf3e8c14aeefc55a2024-12-07T01:00:09ZengBMJ Publishing GroupBMJ Open2044-60552020-03-0110310.1136/bmjopen-2019-033500Assessing 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 protocolFiona Campbell0John Todd1Tabitha Randell2Daniela Elleri3Gianluca Musolino4Janet M Allen5Sara Hartnell6Malgorzata E Wilinska7Martin Tauschmann8Charlotte Boughton9Nicola Trevelyan10Carlo L Acerini11Korey Hood12Craig Kollman13Judy Sibayan14Roman Hovorka15Professor David Dunger16Atrayee Ghatak17Rachel Besser18Elizabeth Northam19Eleanor Scott20Julia Lawton21Stephane Roze22Nate Cohen23AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG2Singulex, Inc., Alameda, United States of AmericaNottingham Children`s Hospital, Nottingham, UKDepartment of Diabetes, Royal Hospital for Sick Children, Edinburgh, UKWellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UKWellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, University of Cambridge School of Clinical Medicine, Cambridge, UKWellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UKWellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, University of Cambridge School of Clinical Medicine, Cambridge, UKDepartment of Pediatrics and Adolescent Medicine, Medical University of Vienna, Wien, AustriaWellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK5 Southampton Children’s Hospital, University Hospital Southampton NHS Foundation Trust, Southampton, UKDepartment of Paediatrics, University of Cambridge, Cambridge, UKEndocrinology, Stanford University School of Medicine, Stanford, California, USAJaeb Center for Health Research, Tampa, Florida, USAJaeb Centre for Health Research, Tampa, Florida, USAWellcome Trust, MRC Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, UKDepartment of Paediatrics, University of Cambridge, Cambridge, UKDepartment of Diabetes, Alder Hey Children`s NHS Foundation Trust, Liverpool, UK15 Department of Paediatrics, University of Oxford, Oxford, UKMurdoch Children’s Research Institute, Parkville, Victoria, Australia9University of Leeds, Leeds Institute of Cardiovascular and Metabolic MedicineCentre for Population Health Sciences, University of Edinburgh, Edinburgh, UKVyoo Agency Sarl, Lyon, FranceJaeb Center for Health Research, Tampa, Florida, USAIntroduction 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.https://bmjopen.bmj.com/content/10/3/e033500.full
spellingShingle Fiona Campbell
John Todd
Tabitha Randell
Daniela Elleri
Gianluca Musolino
Janet M Allen
Sara Hartnell
Malgorzata E Wilinska
Martin Tauschmann
Charlotte Boughton
Nicola Trevelyan
Carlo L Acerini
Korey Hood
Craig Kollman
Judy Sibayan
Roman Hovorka
Professor David Dunger
Atrayee Ghatak
Rachel Besser
Elizabeth Northam
Eleanor Scott
Julia Lawton
Stephane Roze
Nate Cohen
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
BMJ Open
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
url https://bmjopen.bmj.com/content/10/3/e033500.full
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