Closed-loop in Adults With Type 2 Diabetes

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-in Period:

During a 2-3 week run-in period, participants will use their usual insulin therapy and wear a masked CGM system. At the end of the run-in period, for compliance, at least 10 days of CGM data needs to be recorded. CGM data during the run-in period will be used to assess baseline glucose control before the start of the intervention phase.

Randomisation:

Eligible participants will be randomised in a 1:1 ratio using central randomisation software to fully closed-loop or standard insulin therapy with CGM for 26 weeks. Randomisation will be stratified by site and baseline HbA1c.

Fully closed loop insulin delivery (intervention arm):

Following randomisation, participants in the closed-loop group will receive training on the study CGM, study insulin pump and closed-loop App during a 1-2 hour outpatient session. Competency on the use of the closed-loop system will be evaluated. Further training may be delivered as required. Participants will be advised to use the closed-loop system for the next 26 weeks.

Standard insulin therapy with CGM (control arm):

Following randomisation, participants in the control group will use their usual insulin therapy and the study CGM. Training on the use of the CGM will be provided. Participants will use standard insulin therapy and CGM for the next 26 weeks.

3 month study visit: Weight, waist hip ratio and blood pressure will be measured and a blood sample will be taken for measurement of HbA1c, fasted lipid profile, renal and liver function. Data from the closed-loop system and CGM system will be reviewed. Human factors questionnaires will be completed.

• Proportion of time spent in target glucose range (3.9 to 10.0mmol/L) [Срок оценки: over 26 weeks]
• Mean glucose (mmol/L) [Срок оценки: over 26 weeks]
• Proportion of time spent above target glucose (>10.0mmol/l) [Срок оценки: over 26 weeks]
• Proportion of time spent below target glucose (<3.9mmol/L) [Срок оценки: over 26 weeks]
• Standard deviation of sensor glucose [Срок оценки: over 26 weeks]
• Coefficient of variation of sensor glucose [Срок оценки: over 26 weeks]
• Proportion of time spent below target glucose (<3.5mmol/L) [Срок оценки: over 26 weeks]
• Proportion of time spent below target glucose (<3.0mmol/L) [Срок оценки: over 26 weeks]
• Proportion of time spent above target glucose (>13.9mmol/l) [Срок оценки: over 26 weeks]
• Proportion of time spent above target glucose (>16.7mmol/l) [Срок оценки: over 26 weeks]
• Proportion of time spent above target glucose (>20.0mmol/l) [Срок оценки: over 26 weeks]
• Proportion of participants with HbA1c <7.0% [53mmol/mol] (%) [Срок оценки: at 26 weeks]