The main objective of this study is to determine whether day and night closed-loop insulin delivery for 12 weeks under free living conditions is superior to addition of real-time continuous glucose monitoring in adults with type 1 diabetes and sub-optimal glucose control on insulin pump therapy. This is an open-label, multi centre, randomised, crossover design study, involving a 6 to 8 week run-in period, during which glucose control will be optimised by a professional pump educator, followed by two 3 months study periods during which glucose levels will be controlled either by an automated closed-loop system or by subjects usual insulin pump therapy augmented with real-time continuous glucose monitoring in random order. A total of up to 42 adults (aiming for 30 completed subjects) aged 18 years and older with T1D on insulin pump therapy will be recruited through diabetes clinics and other established methods in participating centres. Subjects who drop out of the study within the first 6 weeks of the first intervention arm will be replaced. Subjects will receive appropriate training in the safe use of closed-loop insulin delivery system. Subjects will have regular contact with the study team during the home study phase including 24/7 telephone support. Subjects will be discouraged from international travel during the first two weeks of closed-loop use. The primary outcome is time spent in target range between 3.9 and 10.0 mmol/L as recorded by CGM (adjusted for potential over-estimation) during home stay. Secondary outcomes are the HbA1c, time spent with glucose levels above and below target, as recorded by CGM, and other CGM-based metrics.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
33
Subject's glucose level will be controlled by the Florence D2A or similar automated closed loop glucose control system. The system comprises of FreeStyle Navigator 2 ® Continuous Glucose Monitoring (CGM) System (Abbott Diabetes Care, Alameda, CA, USA), Dana R Diabecare subcutaneous insulin infusion pump (Sooil Corp. Seoul, South Korea)or similar insulin pump, and MPC-based glucose control algorithm running on a smartphone
Subject glucose level controlled by usual insulin pump therapy in conjunction with real time continuous glucose monitoring (CGM)
Medical University of Graz
Graz, Austria
Profil Institut für Stoffwechselforschung GmbH
Neuss, Germany
University of Cambridge
Cambridge, United Kingdom
Time spent in the target glucose range from 3.9 to 10.0 mmol/l based on subcutaneous glucose monitoring
Time spent in the target glucose range from 3.9 to 10.0 mmol/l based on subcutaneous glucose monitoring (CGM) during the 90 days of home stay. Intention to treat basis.
Time frame: 90 days
HbA1c
Measure of average glycaemic control during study period
Time frame: 90 days
Insulin dose
Total, basal and bolus insulin dose during 90 days of home periods
Time frame: 90 days
Adverse Events
Safety evaluation will comprise the number of episodes of hypoglycaemia, significant ketonemia (\> 3.0mmol/l)as well as nature and severity of any other adverse events
Time frame: 10 months
Utility Evaluation
Utility evaluation is the frequency and duration of use of the closed-loop system at home and time between failures of closed-loop system components.
Time frame: 90 days
Continuous subcutaneous glucose monitoring (CGM) based outcome
Time spent above and below the target glucose 3.9 to 10.0 mmol/l, during the 90 days of home periods
Time frame: 90 days
Continuous subcutaneous glucose monitoring (CGM) based outcome
Average,standard deviation and coefficient of variation of glucose levels during 90 days of home periods
Time frame: 90 days
Continuous subcutaneous glucose monitoring (CGM) based outcome
The time with glucose levels \< 3.5 mmol/l and \<2.8 mmol/l during 90 days of home periods
Time frame: 90 days
Continuous subcutaneous glucose monitoring (CGM) based outcome
The time with glucose levels in the significant hyperglycaemia,(glucose levels \> 16.7 mmol/l during 90 days of home periods
Time frame: 90 days
Continuous subcutaneous glucose monitoring (CGM) based outcome
Low Blood Glucose Index during 90 days of home periods
Time frame: 90 days
Continuous subcutaneous glucose monitoring (CGM) based outcome
Duration of periods when sensor glucose values was below 3.5mmol/l for at least 20 minutes
Time frame: 90 days
Continuous subcutaneous glucose monitoring (CGM) based outcome
The "Area Under the Curve" below 3.5 mmol/l during 90 days home periods
Time frame: 90 days
Continuous subcutaneous glucose monitoring (CGM) based outcome
Between 24 hour period variability: Coefficient of variation of CGM glucose between 24 hour periods (midnight to midnight)
Time frame: 90 days
Continuous subcutaneous glucose monitoring (CGM) based outcome
Glucose concentration in the target range (3.9-10.0mmol/L), and above and below target range based on adjusted CGM. Adjustment described in Hovorka R et. al.; Diabetes Technol Ther 14:1-9, 2012
Time frame: 90 days
Continuous subcutaneous glucose monitoring (CGM) based outcome during overnight period between 23:00 and 08:00
Time spent with CGM glucose concentration in the target range (3.9-8.0mmol/L), Mean CGM glucose levels, The AUC below 3.5mmol/l, CV of CGM glucose levels, Coefficient of variation of CGM glucose between nights and Total insulin dose during overnight period between 23:00 and 08:00
Time frame: 90 days
Continuous subcutaneous glucose monitoring (CGM) based outcome during day period between 08:00 to 23:00
Time spent with CGM glucose concentration in the target range (3.9-10.0mmol/L), Mean CGM glucose levels, The AUC below 3.5mmol/l, CV of CGM glucose levels, Coefficient of variation of CGM glucose between days and Total insulin dose during day period between 08:00 to 23:00
Time frame: 90 days
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.