title: Assessing the effectiveness of 3 months day and night home closed-loop insulin delivery in adults with suboptimally controlled type 1 diabetes: a randomised crossover study protocol.
abstract: BACKGROUND
  Despite therapeutic advances, many people with type 1 diabetes are still unable to achieve optimal glycaemic control, limited by the occurrence of hypoglycaemia. The objective of the present study is to determine the effectiveness of day and night home closed-loop over the medium term compared with sensor-augmented pump therapy in adults with type 1 diabetes and suboptimal glycaemic control.
  
  
  METHODS
  The study will adopt an open label, three-centre, multinational, randomised, two-period crossover study design comparing automated closed-loop glucose control with sensor augmented insulin pump therapy. The study will aim for 30 completed participants. Eligible participants will be adults (≥18 years) with type 1 diabetes treated with insulin pump therapy and suboptimal glycaemic control (glycated haemoglobin (HbA1c)≥7.5% (58 mmol/mmol) and ≤10% (86 mmol/mmol)). Following a 4-week optimisation period, participants will undergo a 3-month use of automated closed-loop insulin delivery and sensor-augmented pump therapy, with a 4-6 week washout period in between. The order of the interventions will be random. All analysis will be conducted on an intention to treat basis. The primary outcome is the time spent in the target glucose range from 3.9 to 10.0 mmol/L based on continuous glucose monitoring levels during the 3 months free living phase. Secondary outcomes include HbA1c changes; mean glucose and time spent above and below target glucose levels. Further, participants will be invited at baseline, midpoint and study end to participate in semistructured interviews and complete questionnaires to explore usability and acceptance of the technology, impact on quality of life and fear of hypoglycaemia.
  
  
  BACKGROUND
  Ethical approval has been obtained at all sites. Before screening, all participants will be provided with oral and written information about the trial. The study will be disseminated by peer-review publications and conference presentations.
  
  
  BACKGROUND
  NCT01961622 (ClinicalTrials.gov).
authors.affiliation: Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
authors.forename: Lalantha
authors.initials: L
authors.lastname: Leelarathna
authors.affiliation: Profil Institut für Stoffwechselforschung GmbH, Neuss, Germany.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Dellweg
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Julia K
authors.initials: JK
authors.lastname: Mader
authors.affiliation: Faculty of Medicine, Department of Human Development and Health, University of Southampton, Southampton, UK.
authors.forename: Katharine
authors.initials: K
authors.lastname: Barnard
authors.affiliation: Profil Institut für Stoffwechselforschung GmbH, Neuss, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Benesch
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Ellmerer
authors.affiliation: Profil Institut für Stoffwechselforschung GmbH, Neuss, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Heinemann
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Kojzar
authors.affiliation: Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
authors.forename: Hood
authors.initials: H
authors.lastname: Thabit
authors.affiliation: Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
authors.forename: Malgorzata E
authors.initials: ME
authors.lastname: Wilinska
authors.affiliation: Center for Health Care Delivery Science, Nemours Children's Health System, Florida, USA.
authors.forename: Tim
authors.initials: T
authors.lastname: Wysocki
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Pieber
authors.affiliation: Profil Institut für Stoffwechselforschung GmbH, Neuss, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Arnolds
authors.affiliation: Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Evans
authors.affiliation: Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
authors.forename: Roman
authors.initials: R
authors.lastname: Hovorka
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007332:Insulin Infusion Systems; D008297:Male; D008991:Monitoring, Physiologic; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human
keywords: Artificial pancreas; Closed-loop; Continuous glucose monitoring; Model predictive control; Type 1 diabetes