Assessing the efficacy, safety and utility of 6-month day-and-night automated closed-loop insulin delivery under free-living conditions compared with insulin pump therapy in children and adolescents with type 1 diabetes: an open-label, multicentre, multinational, single-period, randomised, parallel group study protocol

Abstract

IntroductionClosed-loop systems titrate insulin based on sensor glucose levels, providing novel means to reduce the risk of hypoglycaemia while improving glycaemic control. We will assess effectiveness of 6-month day-and-night closed-loop insulin delivery compared with usual care (conventional or sensor-augmented pump therapy) in children and adolescents with type 1 diabetes.Methods and analysisThe trial adopts an open-label, multicentre, multinational (UK and USA), randomised, single-period, parallel design. Participants (n=130) are children and adolescents (aged ≥6 and <19 years) with type 1 diabetes for at least 1 year, and insulin pump use for at least 3 months with suboptimal glycaemic control (glycated haemoglobin ≥58 mmol/mol (7.5%) and ≤86 mmol/mol (10%)). After a 2–3 week run-in period, participants will be randomised to 6-month use of hybrid closed-loop insulin delivery, or to usual care. Analyses will be conducted on an intention-to-treat basis. The primary outcome is glycated haemoglobin at 6 months. Other key endpoints include time in the target glucose range (3.9–10 mmol/L, 70–180 mg/dL), mean sensor glucose and time spent above and below target. Secondary outcomes include SD and coefficient of variation of sensor glucose levels, time with sensor glucose levels <3.5 mmol/L (63 mg/dL) and <3.0 mmol/L (54 mg/dL), area under the curve of glucose <3.5 mmol/L (63 mg/dL), time with glucose levels >16.7 mmol/L (300 mg/dL), area under the curve of glucose >10.0 mmol/L (180 mg/dL), total, basal and bolus insulin dose, body mass index z-score and blood pressure. Cognitive, emotional and behavioural characteristics of participants and caregivers and their responses to the closed-loop and clinical trial will be assessed. An incremental cost-effectiveness ratio for closed-loop will be estimated.Ethics and disseminationCambridge South Research Ethics Committee and Jaeb Center for Health Research Institutional Review Office approved the study. The findings will be disseminated by peer-review publications and conference presentations.Trial registration numberNCT02925299; Pre-results.

Insulin-delivery methods for children and adolescents with type 1 diabetes

“…In line with this, there is an ongoing clinical trial [ClinicalTrials.gov identifier: NCT03844789] assessing the safety and acceptance of the artificial pancreas, t:slim X2, incorporating Dexcom G6 CGM, coupled with a built-in Control-IQ technology for improving blood-glucose levels among children with type 1 diabetes aged 6-13 years old. 80 Nevertheless 81,82 The DAN05 study is expected to be completed by June 2020 and will measure both primary and secondary outomes. The primary outcome will involve the mean group differences in HbA 1c levels at baseline for the 6-month duration; while the secondary outcomes, such as the time spent between 70 mg/ dl and 180 mg/dl (3.9-10.0 mmol/l) glucose target levels, and time spent above or below the glucose target, as measured by CGMs and other related CGM metrics, will be documented.…”

“…The primary outcome will involve the mean group differences in HbA 1c levels at baseline for the 6-month duration; while the secondary outcomes, such as the time spent between 70 mg/ dl and 180 mg/dl (3.9-10.0 mmol/l) glucose target levels, and time spent above or below the glucose target, as measured by CGMs and other related CGM metrics, will be documented. 81,82 Currently, MiniMed 670G is the only automated insulin-pump system available on the market which automatically adjusts basal insulin delivery depending on the CGM readings. 12 In June 2019, Medtronic launched a home-based study trial [ClinicalTrials.gov identifier: NCT03959423] to evaluate the safety of the MiniMed 780G, advanced hybrid closed-loop sytem for automated basal insulin delivery in adult and pediatric participants with type 1 diabetes aged 7-75 years (n = 250).…”

“…Nevertheless, an ongoing 6-month day-and-night open-label, multicenter, multinational, single-period, randomized, parallel-group clinical trial (DAN05) [ClinicalTrials.gov identifier: NCT02925299] assessing the efficacy, safety and usability of an automated closed-loop insulin delivery [FlorenceM in the US (MiniMed™ 640G insulin pump, Medtronic, CA, USA incorporating the Medtronic Guardian™ Sensor 3 CGM) and FlorenceX in the UK (Dana Diabecare® R insulin pump, SOOIL Development, Seoul, Korea, incorporating the Dexcom G6 CGM)] in comparison with the insulin-pump therapy by measuring HbA 1c levels for controlling the blood glucose among children and adolescents ( n = 130) with type 1 diabetes aged 6–18 years old. 81 , 82 The DAN05 study is expected to be completed by June 2020 and will measure both primary and secondary outomes. The primary outcome will involve the mean group differences in HbA 1c levels at baseline for the 6-month duration; while the secondary outcomes, such as the time spent between 70 mg/dl and 180 mg/dl (3.9–10.0 mmol/l) glucose target levels, and time spent above or below the glucose target, as measured by CGMs and other related CGM metrics, will be documented.…”

The DIY artificial pancreas system: an ethical dilemma for doctors

“…In combination, these systems deliver optimal glucose control, reduce hypoglycaemia and improve quality of life [3]; however, they are not readily available in routine clinical practice. Closed-loop systems have been used in research settings for over a decade, with many studies reporting their use, but commercially available systems are not yet widely available [4][5][6]. This has led some 'tech-savvy' people with diabetes to build their own systems (#wearenotwaiting), using insulin pumps and glucose sensors (continuous glucose monitors or flash glucose monitoring).…”

In vivo investigation of the tissue response to commercial Teflon insulin infusion sets in large swine for 14 days: the effect of angle of insertion on tissue histology and insulin spread within the subcutaneous tissue

“…The number of patients with type 1 and type 2 diabetes worldwide using continuous subcutaneous insulin infusion (CSII) therapy to manage their blood glucose (BG) levels is rising 1. Closed-loop and hybrid closed-loop automated insulin delivery systems have become accessible and show promising results by improving BG control, decreasing the incidence of hypoglycemia, and alleviating some of the burden of the disease 2–4. The weak link in the success of insulin pump therapy and artificial pancreas systems is still the insulin infusion set (IIS), in particular the cannula residing in the subcutaneous tissue of the patient.…”