Closing the Loop in Youth With Type 1 Diabetes in the Home Setting

Study Overview
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Brief Summary
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Type 1 diabetes (T1D) is one of the most common chronic childhood diseases requiring life-long insulin therapy. Children and adolescents with T1D need regular insulin injections or the continuous insulin delivery using an insulin pump in order to keep blood glucose levels normal. The investigators know that keeping blood sugars in the normal range will help prevent long-term diabetes-related complications involving the eyes, kidneys and heart. However, achieving treatment goals can be very difficult as the tighter the investigators try to control blood glucose levels, the greater the risk to develop symptoms and signs of low glucose levels (hypoglycaemia). This is a particular problem at night and one solution is to develop a system whereby the amount of insulin injected is controlled by a computer and is very closely matched to the blood sugar levels on a continuous basis. This can be achieved by what is known as a closed-loop system where a small glucose sensor placed under the skin communicates with a computer containing an algorithm that drives an insulin pump. The investigators have been testing such a system in Cambridge over the last three years in children and have found that this system is effective at preventing nocturnal hypoglycaemia. The next stage of this research is to test the system for a longer period of time at home. In the present study the investigators are planning to study 16 adolescents aged 12-18 years on insulin pump therapy. During 21 nights glucose will be controlled by the computer and during the other 21 nights the subjects will make their own adjustments to the insulin therapy. The investigators will then analyze the data to determine the effect of the computer algorithm in keeping glucose levels between 3.9 and 8 mmol/L (normal levels) and reducing the time they spent with glucose below 3.9 mmol/L (hypoglycaemia). Subjects' response to the use of the system in terms of life-style change, daily diabetes management and fear of hypoglycaemia will be assessed. The investigators will also test for longer term glucose control by measuring glycated haemoglobin and other blood parameters.

Official Title
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An Open-label, Single-centre, Randomised, 2-period Cross-over Study to Assess the Efficacy, Safety and Utility of Real-time Continuous Subcutaneous Glucose Monitoring Combined With Overnight Closed-loop Glucose Control in the Home Setting in Comparison With Real-time Continuous Subcutaneous Glucose Monitoring Alone in Adolescents With Type 1 Diabetes on Subcutaneous Insulin Infusion Pump Therapy.

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Device: Overnight closed-loop


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject is between 12 and 18 years of age (inclusive) The subject has type 1 diabetes, as defined by WHO for at least 1 year or is confirmed C-peptide negative The subject will all have been insulin pump user for at least 3 months, with good knowledge of insulin self-adjustment as judged by the investigator The subject willing to perform regular finger-prick blood glucose monitoring, with at least 4 blood glucose measurements taken every day HbA1c ≤ 10 % based on analysis from central laboratory or equivalent The subject is literate in English Able to accommodate on site or in close proximity member(s) of study team for supervised closed-loop night(s) Exclusion Criteria: Non-type 1 diabetes mellitus including those secondary to chronic disease Any other physical or psychological disease likely to interfere with the normal conduct of the study and interpretation of the study results as judged by the investigator Current treatment with drugs known to interfere with glucose metabolism, eg systemic corticosteroids, non-selective beta-blockers and MAO inhibitors etc Known or suspected allergy against insulin Subjects with clinical significant nephropathy, neuropathy or proliferative retinopathy as judged by the investigator Total daily insulin dose ≥ 2 IU/kg/day Pregnancy, planned pregnancy, or breast feeding Prolonged use of any continuous glucose monitoring devices over the last 1 month prior the study Severe visual impairment Severe hearing impairment Subjects using implanted internal pace-maker -

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum 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 |
| --- | --- |
| Active Comparator: Overnight closed-loop combined with real-time CGM<br> | Device: Overnight closed-loop<br>* The closed-loop system is purpose-built and comprises a hand-held computer containing the algorithm and communicating with the CGM device and the insulin pump.<br>|
| Active Comparator: Real-time CGM alone<br> | Device: Overnight closed-loop<br>* The closed-loop system is purpose-built and comprises a hand-held computer containing the algorithm and communicating with the CGM device and the insulin pump.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Efficacy Outcome | The primary objective of the study is to assess the efficacy of continuous glucose monitoring (CGM) combined with overnight automated closed-loop glucose control in maintaining CGM glucose levels within the target range from 3.9 to 8.0 mmol/L, when compared with the use of CGM alone in the home setting. | At least 7 days of valid CGM nights (midnight-7:30) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary outcomes | As a secondary research question, the safety of overnight automated closed-loop glucose control in terms of number of episodes of severe hypoglycaemia as well as the number of subjects experiencing severe hypoglycaemia and other adverse events. Furthermore, the frequency and duration of use of the closed-loop system will be evaluated. Subjects' perception in terms of life-style change, daily diabetes management and fear of hypoglycaemia will be assessed using questionnaires and a qualitative interview. | At least 7 days of valid CGM nights (midnight-7:30) |