Short Term Closed-loop Glucose Control in Adults With Type 1 Diabetes

Study Overview
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Brief Summary
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The main objective of this study is to determine the feasibility, efficacy and safety of automated closed-loop glucose control in the home setting over a short term period. The data and experienced gained from this study will be utilised in planning future home studies. This is an open-label, three centre, randomised, crossover design, involving two, 8 day (first day in the clinical research facility and seven days at home) study periods during which glucose levels will be controlled either by an automated closed-loop system or by subjects usual insulin pump therapy in random order. A total of up to 24 adults (aiming for 18 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 will receive appropriate training in the safe use of closed-loop insulin delivery system. During the 24 hour in-patient stay subjects will be encouraged to mimic their usual day and will be allowed to walk inside hospital premises. Subjects will be advised to discontinue automated closed-loop insulin delivery and follow their usual insulin pump therapy for periods of strenuous exercise during the 7 day home study phase. 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 time spent with glucose levels above and below target, as recorded by CGM, and other CGM-based metrics, and for the stay at the clinical research facility, time spent in the target range, above and below the target range as measured by plasma glucose.

Official Title
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An Open-label, Three-centre, Randomised, Two-period Crossover Study to Assess the Safety, Efficacy and Utility of Automated Closed-loop Glucose Control in Comparison With Continuous Subcutaneous Insulin Infusion Combined With Continuous Glucose Monitoring in Adults With Type 1 Diabetes - A Combined Clinical Research Facility and Home Study

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Device: FlorenceD or similar closed loop glucose control system
* Device: CSII with real-time 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 3 months currently using insulin Aspart, with good knowledge of insulin self-adjustment including carbohydrate counting HbA1c ≤ 10 % based on analysis from local laboratory The subject is willing to perform regular finger-prick blood glucose monitoring, with at least 6 measurements per day during the 7 day home phase of the study 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 literate in English 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: 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 Total daily insulin dose more than 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 Additional exclusion criteria specific for Austria and Germany Positive results on urine drug screen (amphetamines/metamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates). Positive alcohol breath test. Additional exclusion criteria specific for Germany only Positive reaction to any of the following tests: hepatitis B surface (HBs) antigen, anti-hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus (HIV) 1 antibodies, anti-HIV2 antibodies -

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: Closed Loop Glucose control<br>Subject's glucose level is controlled by the automated closed loop glucose control system | Device: FlorenceD or similar closed loop glucose control system<br>* Subject's glucose level will be controlled by the FlorenceD or similar automated closed loop glucose control system. The system comprises of FreeStyle Navigator® 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 portable computer.<br>|
| Active Comparator: CSII with real-time CGM<br>Subject glucose level controlled by usual insulin pump therapy in conjunction with real time continuous glucose monitoring (CGM) | Device: CSII with real-time CGM<br>* Subject glucose level controlled by usual insulin pump therapy in conjunction with real time 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 from 3.9 to 10.0 mmol/l based on subcutaneous glucose monitoring (CGM) adjusted for sensor error. |  | 7 day home study period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time spent above and below the target glucose (3.9 to 10.0 mmol/l) based on continuous subcutaneous glucose monitoring (CGM) |  | 7 day home study period | 
| Average and standard deviation glucose levels based on continuous subcutaneous glucose monitoring |  | 7 day home study period | 
| The time with glucose levels < 3.5 mmol/l and <2.8 mmol/l based on continuous subcutaneous glucose monitoring |  | 7 Day home study period | 
| The time with glucose levels in the significant hyperglycaemia, as based on continuous subcutaneous glucose monitoring (glucose levels > 16.7 mmol/l) |  | 7 day home study period | 
| Low Blood Glucose Index (LBGI) based on continuous subcutaneous glucose monitoring |  | 7 day Home study period | 
| During 24 hour in-patient stay - Same glucose metrics as during 7 day home stay but calculated based on continuous subcutaneous glucose monitoring (CGM) and plasma glucose measurements. |  | 24 hours | 
| Number of episodes of hypoglycaemia, severe hypoglycaemia as well as nature and severity of any other adverse events. |  | 8 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 1 Diabetes, Closed Loop glucose control, Artificial Pancreas, CSII, CGM