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 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 (