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.
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.
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.
UTILITY: The objective is to determine the acceptability and duration of use of the
CGM and closed-loop system.
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.
End of study assessments:
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. Urinary
ACR will be measured. Human factors questionnaires will be completed and a subset of
participants will participate in interviews. Study devices will be returned and
participants will resume their usual insulin therapy and standard glucose monitoring.
Procedures for safety monitoring during trial:
Standard operating procedures for monitoring and reporting of all adverse events and
adverse device events will be in place, including serious adverse events (SAE), serious
adverse device effects (SADE) and specific adverse events (AE) such as severe
hypoglycaemia.
A data safety and monitoring board (DSMB) will be informed of all serious adverse events
and any unanticipated serious adverse device effects that occur during the study and will
review compiled adverse event data at periodic intervals.
Criteria for withdrawal of subjects on safety grounds:
A participant may terminate participation in the study at any time without necessarily
giving a reason and without any personal disadvantage. An investigator can stop the
participation of a subject after consideration of the benefit/risk ratio. Possible
reasons are:
Participant is unable to demonstrate safe use of study devices as judged by the
investigator
Serious adverse events
Significant protocol violation or non-compliance
Decision by the investigator, or the Sponsor, that termination is in the
participant's best medical interest
Pregnancy, planned pregnancy, or breast feeding
Allergic reaction to insulin or severe allergic reaction to adhesive surface of
infusion set or glucose sensor
Technical grounds (e.g. participant relocates)
