Type 1 Diabetes
Conditions
Keywords
Type 1 diabetes, Closed loop insulin delivery, Continuous subcutaneous glucose monitoring, Continuous subcutaneous insulin infusion
Brief summary
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.
Interventions
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
DEVICECSII with real-time CGM
Subject glucose level controlled by usual insulin pump therapy in conjunction with real time continuous glucose monitoring (CGM)
Sponsors
Profil Institut für Stoffwechselforschung GmbH
Medical University of Graz
University of Cambridge
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. The subject has type 1 diabetes as defined by WHO 2. The subject is 18 years of age or older 3. The subject will have been on an insulin pump for at least 6 months with good knowledge of insulin self-adjustment including carbohydrate counting 4. The subject is treated with one of the rapid acting insulin analogues (Insulin Aspart, Insulin Lispro or Insulin Glulisine) 5. HbA1c ≥7.5% (58mmol/mmol) and ≤ 10% (86 mmol/mmol) based on analysis from central laboratory or equivalent 6. The subject is willing to perform regular finger-prick blood glucose monitoring, with at least 6 measurements per day 7. The subject is willing to wear closed-loop system at home and at work place 8. The subject is willing to follow study specific instructions 9. The subject is willing to upload pump and CGM data at regular intervals 10. Female subjects of child bearing age should be on effective contraception and must have a negative urine-HCG pregnancy test at screening. In addition in Germany, women of childbearing potential must use a highly effective method of birth control, which is defined as those which result in a low failure rate (i.e. less than 1% per year) and must use two independent methods of contraception, e.g. diaphragm and spermicide-coated condom.
Exclusion criteria
1. Non-type 1 diabetes mellitus 2. Any other physical or psychological disease or condition likely to interfere with the normal conduct of the study and interpretation of the study results 3. Current treatment with drugs known to have significant interference with glucose metabolism, such as systemic corticosteroids, as judged by the investigator 4. Known or suspected allergy against insulin 5. Subjects with clinically significant nephropathy, neuropathy or proliferative retinopathy as judged by the investigator 6. Significantly reduced hypoglycaemia awareness as judged by the investigator 7. More than one episode of severe hypoglycaemia as defined by American Diabetes Association (31) in preceding 6 months (Severe hypoglycaemia is defined as an event requiring assistance of another person to actively administer carbohydrates, glucagon, or take other corrective actions). 8. Random C-peptide \> 100pmol/l with concomitant plasma glucose \>4 mM(72 mg/dl) 9. Total daily insulin dose \> 2 IU/kg/day 10. Subject is pregnant or breast feeding or planning pregnancy in near future (within next 3 months) 11. Severe visual impairment 12. Severe hearing impairment 13. Subjects using implanted internal pacemaker 14. Lack of reliable telephone facility for contact 15. Subject not proficient in English (UK) or German (Germany and Austria) 16. Subjects who are living alone Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time spent in the target glucose range from 3.9 to 10.0 mmol/l based on subcutaneous glucose monitoring | 90 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | 10 months | 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 |
| Continuous subcutaneous glucose monitoring (CGM) based outcome | 90 days | Time spent above and below the target glucose 3.9 to 10.0 mmol/l, during the 90 days of home periods |
| Continuous subcutaneous glucose monitoring (CGM) based outcome during overnight period between 23:00 and 08:00 | 90 days | 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 |
| Continuous subcutaneous glucose monitoring (CGM) based outcome during day period between 08:00 to 23:00 | 90 days | 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 |
| HbA1c | 90 days | Measure of average glycaemic control during study period |
| Insulin dose | 90 days | Total, basal and bolus insulin dose during 90 days of home periods |
| Utility Evaluation | 90 days | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Effect of study intervention based on pre-study glycaemic control | 90 days | Following outcomes will be calculated separately for participants with baseline HbA1c \<8.5% vs. ≥ 8.5% Time spent with CGM glucose concentration in the target range (3.9-10.0mmol/L), Time spent with CGM glucose levels in hypoglycaemic range (\< 3.9 mmol/L), Time spent with CGM glucose levels in hyperglycaemic range (\> 10.0 mmol/L), Mean CGM glucose levels and the AUC below 3.5mmol/l based on continuous subcutaneous glucose monitoring |
| Accuracy of CGM | 90 days | CGM accuracy during 3 months home period; Capillary glucose vs. CGM will be evaluated using standard measures of numerical and clinical accuracy including absolute relative deviation and error grid analysis |
| Per Protocol Analysis | 90 days | Per protocol analysis will be conducted to explore the relationship between usage of study treatments and study outcomes. |
Countries
Austria, Germany, United Kingdom
Outcome results
None listed