Automated Fully Closed-Loop Insulin Delivery in Type 1 Diabetes With Ultra-Rapid Lispro (ACOLYTE Study)

The main objective of the study is to determine whether fully closed-loop insulin delivery using ultra-rapid acting insulin lispro will improve glucose control compared to standard lispro under conditions mimicking missed meal bolus. Ultra-rapid acting lispro (Lyumjev) is a novel formulation of insulin lispro in which two additional excipients (citrate and trepostinil) have been added, resulting in accelerated initial absorption and more than double the glucose lowering effect in the first 30 minutes after subcutaneous administration using insulin pump. To date, no randomised controlled trial involving fully closed-loop in type 1 diabetes has been performed to evaluate the benefit of Lyumjev over standard lispro. This is an open-label, single-centre, two-period, randomised, crossover study. The study involves two 12-hour in-patient stays at the clinical research facility during which glucose levels will be controlled by the Cambridge closed-loop system with either Lyumjev or standard lispro. Up to 26 adults with type 1 diabetes treated with insulin pump will be recruited at Manchester Royal Infirmary, aiming for 19 completed participants. During the study days, closed-loop will automatically modulate insulin infusion rate based on real-time glucose sensor measurements. Participants will receive standardised meals with no meal bolus for the lunch time meal during each study day. Primary outcome is the time spent in sensor glucose range (3.9-10.0mmol/l) between 11:00 - 17:00 hrs. Secondary outcomes are the time spent with glucose levels above and below target, and other sensor-based metrics. Safety evaluation comprises assessment of the frequency of hypo and hyperglycaemic episodes.