Closing the Loop in Adults With Type 1 Diabetes - Alcohol Consumption

Study Overview
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Brief Summary
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The main objective is to assess the efficacy and safety of overnight automated closed loop glucose control using a computer-based algorithm compared with conventional insulin pump therapy in adults with type 1 diabetes following the consumption of a moderate amount of alcohol at dinnertime.

Detailed Description
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People with type 1 diabetes need regular insulin injections or continuous delivery of insulin using an insulin pump. Keeping blood sugars in the normal range is known to reduce the risk of long term complications involving the eyes, kidneys and heart. However, achieving treatment goals can be very difficult as the tighter we try to control blood glucose levels, the greater the risk of the person developing episodes of low glucose levels (hypoglycaemia). One solution is using a system where the amount of insulin injected closely matches 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 a subcutaneous insulin pump. This system is being developed in Cambridge and is undergoing trials in children and adults with type 1 diabetes. Results thus far show that the system is very effective at preventing hypoglycaemia and maintaining blood glucose levels in target range. We plan to test the closed loop in various challenging conditions faced by patients in daily life. One of these is the consumption of alcohol, which can give rise to delayed hypoglycaemia in patients with diabetes. The studies will be done in a clinical research facility under supervised conditions. Subjects will attend for two study nights where they will receive a specific volume of alcohol with an evening meal. On one night this will be followed by closed loop algorithm control of their insulin overnight. On the other (control) night subjects will remain on their usual pump therapy regime overnight.

Official Title
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Randomised, Two-Period Crossover Study to Assess the Efficacy of Overnight Computer-based Glucose Control Compared With Conventional Pump Therapy Following the Consumption of Alcohol in Adults With Type 1 Diabetes

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Device: Closed loop
* Device: 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 results Known/suspected allergy against insulin Clinically significant nephropathy, neuropathy or retinopathy as judged by the investigator Unstable blood glucose control, including recurrent severe hypoglycaemia as judged by the investigator Current pregnancy/breastfeeding Total daily insulin dose > 1.4 IU/kg HbA1C > 10% within the last 3 months Unable/unwilling to consume the necessary quantity of alcohol stated in the study protocol

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>Subcutaneous delivery of Novorapid insulin, dose calculated by computer-driven control algorithm, based on continuous glucose sensor readings | Device: Closed loop<br>* Subcutaneous delivery of Novorapid insulin, dose calculated by control algorithm, based on continuous glucose sensor readings<br>|
| Placebo Comparator: Open loop<br>Subcutaneous delivery of Novorapid insulin according to usual pump regime | Device: 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 plasma glucose values in target (3.9-8.0 mmol/L) |  | 2200-1200hr | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of CGM (continuous glucose monitoring) values in target (3.9-8.0 mmol/L) |  | 2200-1200; 0000-0400; 0400-0800; 0800-1200; 0300-1200hrs | 
| Percentage of plasma glucose and CGM values in target (3.9-8.0 mmol/L) |  | 0000-0400; 0400-0800; 0800-1200; 0300-1200hrs | 
| Percentage of plasma glucose and CGM values below 3.9 mmol/L |  | 2200-1200; 0000-0400; 0400-0800; 0800-1200; 0300-1200hrs | 
| Percentage of plasma glucose and CGM values above 8.0 mmol/L |  | 2200-1200; 0000-0400; 0400-0800; 0800-1200; 0300-1200hrs | 
| Average plasma and CGM glucose |  | 2200-1200; 0000-0400; 0400-0800; 0800-1200; 0300-1200hrs | 
| Average plasma insulin concentration |  | 2200-1200; 0000-0400; 0400-0800; 0800-1200; 0300-1200hrs | 
| Total dose of insulin administered |  | 2200-1200hrs | 
| Low blood glucose index (LBGI) score |  | 2200-1200; 0000-0400; 0400-0800; 0800-1200; 0300-1200hrs | 
| High blood glucose index (HBGI) score |  | 2200-1200; 0000-0400; 0400-0800; 0800-1200; 0300-1200hrs | 
| Percentage of plasma glucose and CGM values below 3.0 mmol/L |  | 2200-1200; 0000-0400; 0400-0800; 0800-1200; 0300-1200hrs |