Closed-loop in Adults With Type 2 Diabetes

The main objective of this study is to determine the efficacy, safety and utility of fully closed-loop glucose control in the home setting in adults with type 2 diabetes (T2D). This study builds on previous and on-going studies of closed-loop systems that have been performed in Cambridge in adults with type 2 diabetes in the inpatient and in the home setting and in children and adults with type 1 diabetes. This is an open-label, multi-national, multi-centre, randomised, single-period parallel study, involving a run-in period followed by a 26-week intervention period during which glucose levels will be controlled either by a fully closed-loop system or by participants usual insulin therapy with continuous glucose monitoring. A total of up to 224 adults with type 2 diabetes using insulin will be recruited through outpatient diabetes clinics, primary care centres, social media advertising and other established methods at participating centres. Participants will receive appropriate training in the safe use of the study devices. The primary outcome is the between group difference in HbA1c at 26 weeks. Other key outcomes include the time spent with glucose levels within, above and below the target glucose range (3.9-10.0mmol/L) and mean sensor glucose as recorded by CGM over the 26 weeks. Insulin requirements, body weight, renal and liver function will also be compared. Safety evaluation comprises severe hypoglycaemic episodes, and other adverse and serious adverse events. Human factors outcomes include CGM \& closed-loop usage, questionnaires and semi-structured interviews.

Purpose of clinical trial: To determine the efficacy, safety and utility of fully closed-loop insulin delivery over 26 weeks in the home setting in adults with type 2 diabetes. Study objectives: To determine the efficacy, safety and utility of fully closed-loop insulin delivery over 26 weeks in the home setting in adults with type 2 diabetes. 1. EFFICACY: The objective is to assess the ability of fully closed-loop insulin delivery to improve glucose control as measured by HbA1c (primary endpoint) and sensor glucose metrics. 2. SAFETY: The objective is to evaluate the safety of fully closed-loop insulin delivery in terms of episodes and severity of hypoglycaemia, and nature and severity of other adverse events. 3. UTILITY: The objective is to determine the acceptability and duration of use of the CGM and closed-loop system. 4. HUMAN FACTORS: The objective is to assess cognitive, emotional, and behavioural characteristics of participants and their response to the closed-loop system using validated questionnaires and semi-structured interviews. Participating clinical centres: UK - Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust. - Imperial College Healthcare NHS Trust, London \- Manchester Royal Infirmary, Manchester University NHS Foundation Trust \- King's College Hospital, King's College Hospital NHS Foundation Trust, London \- Guy's and St Thomas' NHS Foundation Trust \- Norfolk and Norwich University Hospital, Norfolk and Norwich University Hospitals NHS Foundation Trust \- University Hospitals of Leicester NHS Trust Switzerland \- Inselspital, Bern University Hospital, Bern France \- Centre Hospitalier Universitaire (CHU) de Toulouse Germany \- Medical Center - University of Freiburg Austria \- Medical University of Graz, Graz Czech Republic \- Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague Sample Size: 224 participants (112 per group) will be randomised. Recruitment will target a minimum quota of 25% of participants using basal insulin and a minimum quota of 60% of participants using multiple daily insulin injections. Maximum duration of study for a subject: 30 weeks Recruitment: Participants will be recruited through outpatient diabetes clinics, primary care centres, social media advertising or other established methods at participating centres Consent: Participants will be asked to provide written informed consent. Baseline Assessment: Eligible participants will undergo baseline evaluation involving talking a medical history including demographics, height/weight, waist hip ratio and blood pressure measurement and blood samples for HbA1c, fasted lipid profile, renal and liver function. A urine albumin-creatinine ratio (ACR) will be performed, along with a urine pregnancy test in females of child-bearing age. Human factors questionnaires will be completed and a masked glucose sensor will be applied. Run-i trial.show_full_description

Inclusion Criteria: * Aged 18 years and older * Type 2 diabetes diagnosed for at least 12 months * Established on an SGLT2 inhibitor and/or GLP-1 receptor agonist for at least 3 months, or have been offered these therapies previously. * Treatment with insulin therapy for at least 6 months * HbA1c ≤ 15% (140 mmol/mol) analysis from local laboratory or equivalent * Willing to wear study devices and follow study instructions * Capacity to consent to participate in the study Exclusion Criteria: * Type 1 diabetes * Current use of insulin pump * Current use of any closed-loop system * Any physical/psychological disease or medication(s) likely to interfere with the conduct of the study and interpretation of the study results, as judged by study clinician * Known or suspected allergy against insulin * Medically documented allergy towards the adhesive * Pregnancy, planned pregnancy, or breast feeding * Severe visual impairment * Severe hearing impairment * Medically documented allergy towards the adhesive (glue) of plasters * Serious skin diseases located at places of the body, which potentially are possible to be used for localisation of the glucose sensor * Illicit drugs abuse * Prescription drugs abuse * Alcohol abuse