Closing the Loop in Young Children With Type 1 Diabetes

Study Overview
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Brief Summary
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The incidence of type 1 diabetes (T1D) is increasing worldwide with evidence of most rapid increase in preschool children. Intensive control of blood glucose levels, although essential to protect against onset and progression of diabetes-related complications, faces unique challenges in toddlers and preschool children. A closed-loop system can enhance accuracy of insulin delivery and help people with T1D attain a tight glucose control avoiding the risk of hypoglycaemia. The main components of the system are a continuous glucose monitor (CGM), an insulin pump and a computer-based 'model predictive algorithm', which calculates the amount of insulin to be given by the insulin pump according to the CGM values. In the studies performed thus far the efficacy and safety of closed-loop glucose control were evaluated in children and adolescents aged 6 to 18 years. The results showed that closed-loop improved control of blood glucose and prevented nocturnal hypoglycaemia, as compared to the conventional insulin pump therapy. The objective of the current study is to extend the evaluation of closed-loop further to younger children aged 2 to 6 years, who may gain a great benefit from this novel therapy. The present study adopts an open-label, randomised, 2 period cross-over design whereby closed-loop insulin therapy using diluted insulin (20IU/ml)will be compared with closed-loop with standard insulin (100IU/ml)in 12 young children with T1D. Participants aged 2 to 6 years will be randomised for two overnight studies in a clinical research facility, during which glucose levels will be controlled by either the computer-based closed-loop algorithm using diluted insulin or by closed-loop with standard insulin. On both occasions, participants will receive a self-selected evening meal and closed-loop will run from 17:00 until 08:00am the following day. The study will take place at the Wellcome Trust Clinical Research Facility, Cambridge with participants recruited from paediatric diabetes clinics in England.

Official Title
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An Open-label, Single-centre, Randomised, 2-period Cross-over Study to Assess the Efficacy and Safety of Overnight Closed-loop Insulin Delivery Using Diluted Insulin in Comparison With Closed-loop With Non-diluted Insulin in Children With Type 1 Diabetes Aged 2 to 6 Years

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Procedure: Overnight closed-loop insulin delivery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject is between 2 and 6 years of age (inclusive) The subject has had type 1 diabetes, as defined by WHO criteria for at least 6 months The subject will be an insulin pump user and carers will have a good knowledge of insulin dose adjustment HbA1c below 12 % (108mmol/mol) 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 Current treatment with drugs known to interfere with glucose metabolism such as systemic corticosteroids Known or suspected allergy against insulin

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 6 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 with diluted insulin<br>Insulin pump therapy using diluted insulin (20 IU/ml) will be driven by computer-based algorithm from 1700 on Day 1 until 0800 on Day 2 | Procedure: Overnight closed-loop insulin delivery<br>* Basal insulin infusion rates on insulin pump will be directed by MPC algorithm using diluted versus non-diluted insulin<br>|
| Active Comparator: Closed-loop with non-diluted insulin<br>Insulin pump therapy using standard non-diluted insulin (100 IU/ml) will be driven by computer-based algorithm from 1700 on Day 1 until 0800 on Day 2 | Procedure: Overnight closed-loop insulin delivery<br>* Basal insulin infusion rates on insulin pump will be directed by MPC algorithm using diluted versus non-diluted insulin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time in target | Time spent with plasma glucose concentration in the target range (3.9-8.0mmol/L) | Between 21:00 on Day 1 and 8:00 on Day 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time below target | • Time spent with plasma glucose concentration below the target range (<3.9mmol/L) | Between 21:00 on Day 1 and 8:00 on Day 2 | 
| Glucose variability | • Glucose variability as measured by standard deviation of glucose | Between 21:00 on Day 1 and 08:00 on Day 2 |