The Co-Pilot trial: Closed loop in children and youth with type 1 diabetes and high-risk glycaemic control

INTERVENTION: This is a 3‐month randomized controlled trial (RCT) followed by a 9‐month extension phase investigating advanced hybrid closed loop (AHCL) in children and youth with type 1 diabetes (T1D) and high‐risk glycaemic control that have previously not been using closed loop therapy. Following baseline assessments of blinded continuous glucose monitoring (CGM) for 21 days (using Guardian 3 sensor and transmitter CGM system), participants will be randomized to AHCL use (intervention group) or their usual diabetes management care (control group). The intervention group will undergo a run‐in period of 72 hours running as sensor augmented pump (SAP) with predictive low glucose monitoring (PLGM) to allow subjects to familiarize with the system and for control to be optimized, and will then enter into a 3‐month study period of using the insulin pump in its trial settings in Auto mode. All participants will use the AHCL system in Auto mode for a further 9 months during the extension phase. While participants have the option to enable/disable Auto mode during the RCT and extension phase, the AHCL system provides optimal results in Auto mode and therefore participants are encouraged to keep the system in Auto mode during the study. Expected duration of subject participation is 13 months (21 days baseline assessments, 3 days run‐in, 3 months RCT, 9 months extension). The study intervention is the Medtronic MiniMed™ 780G AHCL insulin pump running in AHCL mode. In use with the continuous glucose monitoring (CGM) components (Guardian 4 Sensor and Guardian 4 transmitter, and Medtronic's newest Synergy CGM system), the MiniMed™ 780G AHCL pump is capable of continuous insulin delivery at set and variable rates, and the monitoring of glucose levels via a sensor that is inserted in the inter CONDITION: Metabolic and Endocrine ‐ Diabetes Type 1 diabetes; ; Type 1 diabetes PRIMARY OUTCOME: Glycaemic control as measured by glycated hemoglobin (HbA1C) from blood samples.[At baseline, at 3 months post‐RCT commencement (primary endpoint), and at 3, 6, and 9 months post‐extension phase commencement. ] INCLUSION CRITERIA: 1. Male or female aged 7 – 25 years inclusive. 2. Type I diabetes as per the American Diabetes Association Classification, diagnosed at least 1 year prior to Study Day 1. 3. Current HbA1c level of greater than or equal to 8.5% (69mmol/mol). 4. Minimum daily insulin requirement of greater than or equal to 8 units of insulin/day. 5. Willing and able to adhere to the study protocol. 6. Access to the internet and a computer system that meets requirements for uploading the study pump. SECONDARY OUTCOME: Glucose levels during the day (0600‐2359 hours), determined from CGM data.[At baseline, at 3 months post‐RCT commencement, and at 3, 6, and 9 months post‐extension phase commencement. ] Glucose levels during the night (0000‐0559 hours), determined from CGM data.[At baseline, at 3 months post‐RCT commencement, and at 3, 6, and 9 months post‐extension phase commencement. ] Glycaemic control as measured by percentage of time in range (3.9 – 10mmol/L), by way of CGM data analysis.[At baseline, at 3 months post‐RCT commencement, and at 3, 6, and 9 months post‐extension phase commencement. ] Glycaemic outcomes via CGM data for % CGM time above 10.0mmol/L[At baseline, at 3 months post‐RCT commencement, and at 3, 6, and 9 months post‐extension phase commencement. ] Glycaemic outcomes via CGM data for % CGM time above 13.9mmol/L[At baseline, at 3 months post‐RCT commencement, and at 3, 6, and 9 months post‐extension phase commencement. ] Glycaemic outcomes via CGM data for % CGM time below 3.0mmol/L[At baseline, at 3 months post‐RCT commencement, and at 3, 6, and 9 months post‐extension phase commencement. ] Glycaemic outcomes via CGM data for % CGM time below 3.9mmol/L[At baseline, at 3 months post‐RCT commencement, and at 3, 6, and 9 months post‐extension phase commencement. ] Platform performance as measured by percentage of insulin delivery distribution, determined by accessing device analytics via the CareLinkTM software. [At baseline, at 3 months post‐RCT commencement, and at 3, 6, and 9 months post‐extension phase commencement. ] Platform performance as measured by percentage of time of sensor wear, determined by accessing device analytics via the CareLinkTM software. [At baseline, at 3 months post‐RCT commencement, and at 3, 6, and 9 months post‐extension phase commencement. ] Platform performance as measured by percentage of time spent in automode, determined by accessing device analytics via the CareLinkTM software. [At baseline, at 3 months post‐RCT commencement, and at 3, 6, and 9 months post‐extension phase commencement. ] Qualitative interview‐based assessment of participant experience using AHCL. Semi‐structured, one‐on‐one interviews with trained members of the study team will be conducted face‐to‐face in private clinic rooms, or via videoconference (Zoom). Interviews will take approximately 45‐60 minutes, will be digitally recorded and transcribed verbatim. [After 13 weeks of pump use in Auto mode] Safety of AHCL system, as determined by occurrence of episodes of diabetic ketoacidosis from participant self‐reports and data linkage to medical records.[At baseline, at 3 months post‐RCT commencement, and at 3, 6, and 9 months post‐extension phase commencement. ] Safety of AHCL system, as determined by occurrence of episodes of severe hypoglycaemia defined as coma or convulsion requiring assistance from others, from participant self‐reports and data linkage to medical records.[At baseline, at 3 months post‐RCT commencement, and at 3, 6, and 9 months post‐extension phase commencement. ] The change in diabetes treatment satisfaction as measured by the Diabetes Treatment Satisfaction Questionnaire‐status (DTSQs)[At baseline, at 3 months post‐RCT commencement.] The change in fear of hypoglycaemia as measured by the Hypoglycaemia Fear Survey (HFS)[At baseline, and at 3 months post‐RCT commencement.] The change in feelings towards automated insulin dosing systems as measured by the INSPIRE survey.[At baseline, at 3 months post‐RCT commencement.] The change in sleep quality, as measured by the Pittsburgh Sleep Quality Inde X(PSQI)[At baseline, at 3 months post‐RCT commencement.]