Automated Closed-loop in Children and Adolescents With Type 1 Diabetes
Condition: Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Endocrine System Diseases; Autoimmune Diseases
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Metabolic Diseases; Glucose Metabolism Disorders; Endocrine System Diseases; Autoimmune Diseases
Study type: Interventional

Summary: 
      People with type 1 diabetes need regular insulin injections or continuous delivery of insulin
      using a pump. Keeping blood sugars in the normal range is known to reduce long term
      complications. However, achieving treatment goals can be very difficult due to the risk of
      low glucose levels (hypoglycaemia). One solution is to use 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. Previous studies conducted under carefully controlled clinical research
      facility environment, in Cambridge, United Kingdom, as well as several other centres have
      shown that closed-loop glucose control is superior to usual insulin pump therapy. The next
      logical step in the development pathway is to test closed loop systems in the home
      environment. An essential requirement for conducting closed-loop studies outside clinical
      research facility is an automated system where wireless data transmission takes place between
      the glucose sensor and insulin pump.

      The purpose of the present study is to evaluate the efficacy and safety of automated
      overnight closed-loop, in children and adolescents with type 1 diabetes, using a novel system
      which has greatest potential for use in the home setting. The study will take place at a
      clinical research facility on two occasions, using a standardised protocol. The performance
      of the closed-loop system will be evaluated on day 1 of continuous glucose monitoring (CGM)
      sensor life as compared to on days 3 to 4 of sensor life. Data and experience gained from
      this study will be used for further refinements and development of the system for future home
      use.
    

Detailed description: 
      The main objective of the current study is to evaluate the efficacy, safety and
      utility/reliability of a novel automated overnight closed-loop glucose control system in
      children and adolescents with type 1 diabetes. This will inform the future development of
      closed-loop systems in children and adolescents aged 6 to 18 years with type 1 diabetes.

      This is an open-label, randomised, 2-period cross-over study, using the Medtronic Android
      closed loop platform or similar, comparing the safety and efficacy of overnight closed loop
      glucose control on day 1 compared with day 3 to 4 of CGM sensor life. Participants will be
      randomised to undergo two overnight studies in a clinical research facility, during which
      glucose levels will be controlled by the computer-based closed-loop algorithm on day 1 of CGM
      sensor insertion or day 3 to 4 after sensor insertion.

      A total of 16 children and adolescents with T1D between 6 and 18 years of age will be
      recruited through the Outpatient Diabetes Clinic in the Department of Paediatrics,
      Addenbrooke's Hospital and Paediatric Diabetes Centres in London, Norwich, and Ipswich, to
      allow for 12 available for assessment. All participants will be on insulin pump treatment
      with a good knowledge of insulin dose adjustments. The study will take place at the Wellcome
      Trust Clinical Research Facility (WTCRF), Cambridge. Participants will be admitted at the
      clinical research facility in the evening and stay until the following morning. During the
      two closed-loop visits, automated closed-loop glucose control with wireless data transmission
      will be performed. A Model-Predictive-Control algorithm will determine the insulin infusion
      rate based on interstitial glucose measured by a continuous subcutaneous glucose monitoring
      (CGM) system. Intravenous sampling for glucose and insulin levels will also be carried out on
      both study visits for post hoc validation of glucose sensor data and for future modelling
      purposes.

      The primary efficacy endpoint is the time spent in the target plasma glucose range from 3.9
      to 8 mmol/L. Safety evaluation is focused on the frequency and duration of episodes of
      hypoglycaemia.
    

Intervention name(s): Closed-loop (Android Closed-Loop platform)
Intervention type(s): Device
Intervention description(s): The closed-loop system is purpose-built and comprises a hand-held computer containing a model predictive control (MPC) based glucose control algorithm and communicating with the CGM device and the insulin pump.
The Android Closed-Loop platform employs the Medtronic MiniMed Paradigm® Veo™ insulin pump system with CGM capability (use of MiniLink™Transmitter and sensor). A Radiofrequency (RF) translator module translates the RF protocol to Bluetooth® technology. An Android device containing an algorithm will use sensor glucose data to calculate pump strokes.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Type 1 diabetes; Closed-loop glucose control; Artificial Pancreas; Continuous subcutaneous insulin infusion; Continuous glucose monitoring