title: Day and night glycaemic control with a bionic pancreas versus conventional insulin pump therapy in preadolescent children with type 1 diabetes: a randomised crossover trial.
abstract: BACKGROUND
  The safety and efficacy of continuous, multiday, automated glycaemic management has not been tested in outpatient studies of preadolescent children with type 1 diabetes. We aimed to compare the safety and efficacy of a bihormonal bionic pancreas versus conventional insulin pump therapy in this population of patients in an outpatient setting.
  
  
  METHODS
  In this randomised, open-label, crossover study, we enrolled preadolescent children (aged 6-11 years) with type 1 diabetes (diagnosed for ≥1 year) who were on insulin pump therapy, from two diabetes camps in the USA. With the use of sealed envelopes, participants were randomly assigned in blocks of two to either 5 days with the bionic pancreas or conventional insulin pump therapy (control) as the first intervention, followed by a 3 day washout period and then 5 days with the other intervention. Study allocation was not masked. The autonomously adaptive algorithm of the bionic pancreas received data from a continuous glucose monitoring (CGM) device to control subcutaneous delivery of insulin and glucagon. Conventional insulin pump therapy was administered by the camp physicians and other clinical staff in accordance with their established protocols; participants also wore a CGM device during the control period. The coprimary outcomes, analysed by intention to treat, were mean CGM-measured glucose concentration and the proportion of time with a CGM-measured glucose concentration below 3·3 mmol/L, on days 2-5. This study is registered with ClinicalTrials.gov, number NCT02105324.
  
  
  RESULTS
  Between July 20, and Aug 19, 2014, 19 children with a mean age of 9·8 years (SD 1·6) participated in and completed the study. The bionic pancreas period was associated with a lower mean CGM-measured glucose concentration on days 2-5 than was the control period (7·6 mmol/L [SD 0·6] vs 9·3 mmol/L [1·7]; p=0·00037) and a lower proportion of time with a CGM-measured glucose concentration below 3·3 mmol/L on days 2-5 (1·2% [SD 1·1] vs 2·8% [1·2]; p<0·0001). The median number of carbohydrate interventions given per participant for hypoglycaemia on days 1-5 (ie, glucose <3·9 mmol/L) was lower during the bionic pancreas period than during the control period (three [range 0-8] vs five [0-14]; p=0·037). No episodes of severe hypoglycaemia were recorded. Medium-to-large concentrations of ketones (range 0·6-3·6 mmol/dL) were reported on seven occasions in five participants during the control period and on no occasion during the bionic pancreas period (p=0·063).
  
  
  CONCLUSIONS
  The improved mean glycaemia and reduced hypoglycaemia with the bionic pancreas relative to insulin pump therapy in preadolescent children with type 1 diabetes in a diabetes camp setting is a promising finding. Studies of a longer duration during which children use the bionic pancreas during their normal routines at home and school should be done to investigate the potential for use of the bionic pancreas in real-world settings.
  
  
  BACKGROUND
  The Leona M and Harry B Helmsley Charitable Trust and the US National Institute of Diabetes and Digestive and Kidney Diseases.
authors: Diabetes Unit and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors: Steven J
authors: SJ
authors: Russell
authors: Diabetes Unit and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors: Mallory A
authors: MA
authors: Hillard
authors: Diabetes Unit and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors: Courtney
authors: C
authors: Balliro
authors: Diabetes Unit and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors: Kendra L
authors: KL
authors: Magyar
authors: Department of Biomedical Engineering, Boston University, Boston, MA, USA.
authors: Rajendranath
authors: R
authors: Selagamsetty
authors: Diabetes Unit and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors: Manasi
authors: M
authors: Sinha
authors: Diabetes Unit and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors: Kerry
authors: K
authors: Grennan
authors: Diabetes Unit and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors: Debbie
authors: D
authors: Mondesir
authors: Diabetes Unit and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors: Laya
authors: L
authors: Ekhlaspour
authors: Biostatistics Center, Massachusetts General Hospital, Boston, MA, USA.
authors: Hui
authors: H
authors: Zheng
authors: Department of Biomedical Engineering, Boston University, Boston, MA, USA. Electronic address: edamiano@bu.edu.
authors: Edward R
authors: ER
authors: Damiano
authors: Department of Biomedical Engineering, Boston University, Boston, MA, USA.
authors: Firas H
authors: FH
authors: El-Khatib
mesh_terms: D001786:Blood Glucose / Q000187:drug effects; D002648:Child; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000628:therapy*; D005260:Female; D005934:Glucagon / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use*; D007332:Insulin Infusion Systems / Q000009:adverse effects*; D008297:Male; D008991:Monitoring, Physiologic; D019397:Pancreas, Artificial / Q000009:adverse effects*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D005934:Glucagon