Closing the Loop in Adults With Type 1 Diabetes and HbA1C<7.5% Under Free Living Conditions

Study Overview
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Brief Summary
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The main objective of this study is to determine whether day and night closed-loop insulin delivery for 4 weeks under free living conditions is superior to usual insulin pump therapy in adults with type 1 diabetes and HbA1C<7.5%. This is an open-label, multi center, randomized, crossover design study, involving a 2-4 week run-in period, followed by two 4 weeks study periods during which glucose levels will be controlled either by an automated day- and night closed-loop system or by subjects usual insulin pump therapy in random order. A total of up to 34 adults (aiming for 24 completed subjects) aged 18 years and older with T1D on insulin pump therapy and HbA1C<7.5% will be recruited through diabetes clinics and other established methods in participating centers. 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. The primary outcome is time spent in target range between 3.9 and 10.0 mmol/L as recorded by CGM during home stay. Secondary outcomes are time spent with glucose levels above and below target, as recorded by CGM, and other CGM-based metrics.

Official Title
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Closing the Loop in Adults With Type 1 Diabetes and HbA1C<7.5% Under Free Living Conditions

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Device: Florence D2A or similar closed loop glucose control system
* Device: CSII with CGM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject has type 1 diabetes as defined by WHO The subject is 18 years of age or older The subject will have been on an insulin pump for at least 6 months with good knowledge of insulin self-adjustment including carbohydrate counting The subject is treated with one of the rapid acting insulin analogues (Insulin Aspart, Insulin Lispro or Insulin Glulisine) HbA1c <7.5% (58mmol/mmol) based on analysis from central laboratory or equivalent The subject is willing to perform regular finger-prick blood glucose monitoring, with at least 6 measurements per day The subject is willing to wear closed-loop system at home and at work place The subject is willing to follow study specific instructions The subject is willing to upload pump and CGM data at regular intervals Female subjects of child bearing age should be on effective contraception and must have a negative urine-HCG pregnancy test at screening. Exclusion Criteria: Non-type 1 diabetes mellitus Any other physical or psychological disease or condition likely to interfere with the normal conduct of the study and interpretation of the study results Current treatment with drugs known to have significant interference with glucose metabolism, such as systemic corticosteroids, as judged by the investigator Known or suspected allergy against insulin Subjects with clinically significant nephropathy, neuropathy or proliferative retinopathy as judged by the investigator Significantly reduced hypoglycaemia awareness as judged by the investigator More than one episode of severe hypoglycaemia as defined by American Diabetes Association 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). Random C-peptide > 100pmol/l with concomitant plasma glucose >4 mM(72 mg/dl) Total daily insulin dose > 2 IU/kg/day Subject is pregnant or breast feeding or planning pregnancy in near future (within next 3 months) Severe visual impairment Severe hearing impairment Subjects using implanted internal pacemaker Lack of reliable telephone facility for contact Subject not proficient in English (UK) or German (Austria) Subjects who are living alone Additional exclusion criteria specific for Austria: Positive results on urine drug screen (amphetamines/metamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates). Additional exclusion criteria specific for Austria:Positive alcohol breath test.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: day and night closed loop control<br>Subjects glucose levels are controlled by Florence D2A or similar closed loop insulin delivery system | Device: Florence D2A or similar closed loop glucose control system<br>* 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<br>|
| Active Comparator: usual insulin pump therapy management<br>Subject glucose level controlled by usual insulin pump therapy in conjunction with continuous glucose monitoring (FreeStyle Navigator CGM) | Device: CSII with CGM<br>* Subject glucose level controlled by usual insulin pump therapy in conjunction with continuous glucose monitoring (CGM)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time spent in the target glucose range (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 4 weeks of home stay. Intention to treat basis. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Continuous subcutaneous glucose monitoring (CGM) based outcome | Time spent above and below the target glucose range from 3.9 to 10.0 mmol/l based on subcutaneous glucose monitoring (CGM) during the 4 weeks of home stay. Intention to treat basis. | 4 weeks | 
| Continuous subcutaneous glucose monitoring (CGM) based outcome | Average,standard deviation and coefficient of variation of glucose levels during 4 weeks of home periods | 4 weeks | 
| Continuous subcutaneous glucose monitoring (CGM) based outcome | The time with glucose levels < 3.5 mmol/l and <2.8 mmol/l during 4 weeks of home periods | 4 weeks | 
| Continuous subcutaneous glucose monitoring (CGM) based outcome | The time with glucose levels in the significant hyperglycaemia,(glucose levels > 16.7 mmol/l during 4 weeks of home periods | 4 weeks | 
| Continuous subcutaneous glucose monitoring (CGM) based outcome | Low Blood Glucose Index | 4 weeks | 
| Continuous subcutaneous glucose monitoring (CGM) based outcome | The Area Under the Curve below 3.5 mmol/l during 4 weeks home periods | 4 weeks | 
| 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) | 4 weeks | 
| Continuous subcutaneous glucose monitoring (CGM) based outcome during overnight period between 24:00 and 06:00 | Time spent with CGM glucose concentration in range 3.9-10.0mmol/L | 4 weeks | 
| Continuous subcutaneous glucose monitoring (CGM) based outcome during day period between 06:00 to 24:00 | Time spent with CGM glucose concentration in the target range (3.9-10.0mmol/L) | 4 weeks | 
| Insulin dose | Total, basal and bolus insulin dose during 4 weeks of home periods | 4 weeks | 
| 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 | 5 months | 
| Utility Evaluation | Utility evaluation is the percentage of closed-loop operation time during use at home, and when CGM was available | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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closed loop glucose control, hypoglycemia, type 1 diabetes, HbA1C<7.5%