Closing the Loop in Young Children With Type 1 Diabetes

• Time below target [ Time Frame: Between 21:00 on Day 1 and 8:00 on Day 2 ] [ Designated as safety issue: Yes ]
  • Time spent with plasma glucose concentration below the target range (<3.9mmol/L)
• Glucose variability [ Time Frame: Between 21:00 on Day 1 and 08:00 on Day 2 ] [ Designated as safety issue: No ]
  • Glucose variability as measured by standard deviation of glucose

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.

• Experimental: Closed-loop with diluted insulin
  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
  Intervention: Procedure: Overnight closed-loop insulin delivery
• Active Comparator: Closed-loop with non-diluted insulin
  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
  Intervention: Procedure: Overnight closed-loop insulin delivery

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