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

Study Overview
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Brief Summary
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The main study objective is to compare real-time continuous subcutaneous glucose monitoring (CGM) combined with overnight automated closed-loop glucose control, and real-time CGM alone in the home setting.

Detailed Description
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Achievement of tight glycaemic control in type 1 diabetes mellitus (T1D) using intensive insulin regimens, which has been shown to be important for the prevention of long term diabetes-related complications, is limited by a significantly increased risk of hypoglycaemia. The average patient with T1D suffers two symptomatic episodes of hypoglycaemia per week, and one episode of severe hypoglycaemia, defined as an event requiring assistance of another person to administer rescue treatment in the form of carbohydrate and/or glucagon, per year.Despite the rapid advancements in insulin pump technology and the ongoing development of more physiological insulin preparations, the currently available therapeutic regimens are still unable to achieve optimal glycaemic control.The emergence of continuous glucose monitoring (CGM) over the last decade, which enables users to view in real-time estimates of plasma glucose and receive alarms for impending hypo- or hyperglycaemia, thus facilitating appropriate changes in insulin therapy, is a major step towards improved diabetes monitoring. The desirable goal is the development of an insulin delivery that is glucose responsive and the development of effective real time glucose monitoring should allow this. Glucose responsive insulin delivery should allow achievement of ideal glucose targets with less risk of hypoglycaemia. Closed-loop systems may provide a realistic treatment option for people with T1D. The research we are conducting at the University of Cambridge has been focused on developing a closed-loop system for overnight glucose control in patients with T1D. The studies that have been performed so far employ model predictive control (MPC) - this algorithm estimates patient-specific parameters from CGM measurements taken every 1 to 15 minutes and makes predictions of glucose excursions, which are then used to calculate basal insulin infusion rates. We hypothesize that overnight automated closed-loop glucose control in the home setting will be efficacious and safe compared to CGM alone, in T1D subjects on insulin pump treatment.

Official Title
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An Open-label, Three-centre, Randomised, Two-period, Crossover 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 Adults With Type 1 Diabetes on Subcutaneous Insulin Infusion Pump Therapy

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Other: Closed-loop
* Other: Conventional insulin pump delivery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 1 diabetes, as defined by WHO for at least 6 months or confirmed C-peptide negative. On insulin pump therapy for at least 3 months Exclusion Criteria: Non-type 1 diabetes mellitus Any physical/psychological disease likely to interfere with the study Taking medication likely to interfere with interpretation of the results Known/suspected allergy against insulin Patients with clinically significant nephropathy, neuropathy or retinopathy as judged by the investigator Ongoing severe recurrent hypoglycaemia as judged by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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 (algorithm)<br> | Other: Closed-loop<br>* Subcutaneous delivery of Novorapid insulin, dose calculated by control algorithm, based on continuous glucose sensor readings.<br>* Other names: Automated CL;|
| Placebo Comparator: Open loop<br> | Other: Conventional insulin pump delivery<br>* Subcutaneous delivery of Novorapid insulin according to usual pump regime<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of CGM (Continuous glucose monitoring) values in target (3.9 - 8.0 mmol/l). | Participants will be assessed overnight (00:00 to 07:00) for 4 weeks in each arm. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of CGM values below 3.9 mmol/l. | Participants will be assessed overnight (00:00 to 07:00) for 4 weeks in each arm. | 4 weeks | 
| Time spent with glucose levels below 3.9 mmol/l and above 8.0 mmol/l, as recorded by CGM and other CGM-based metrics | Participants will be assessed overnight (00:00 to 07:00) for 4 weeks in each arm. | 4 weeks | 
| Glycaemic control assessed by fructosamine and HbA1c | Participants will be assessed for 4 weeks in each arm. | 4 weeks |