Closing the Loop 24/7 in Adolescents With Type 1 Diabetes
Condition: Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Endocrine System Diseases
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Metabolic Diseases; Glucose Metabolism Disorders; Endocrine System Diseases
Study type: Interventional

Summary: 
      Type 1 diabetes (T1D) is one of the most common chronic childhood diseases requiring lifelong
      insulin therapy. Children and adolescents with T1D need regular insulin injections or the
      continuous insulin delivery using an insulin pump in order to keep blood glucose levels
      normal. We know that keeping blood sugars in the normal range will help prevent long-term
      diabetes-related complications involving the eyes, kidneys and heart. However, achieving
      treatment goals can be very difficult particularly 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. We have been
      testing such a system in Cambridge over the last five years in children and have found that
      this system is effective, and superior to usual insulin pump therapy, at maintaining tight
      glucose control. More recently the system has been tested overnight, in the home setting, for
      three weeks in adolescents during a pilot single-centre study.

      The next step is to evaluate use of the closed loop system day and night over a period of 7
      days (phase 1) and 21 days (phase 2) in adolescents with type 1 diabetes. In the present
      study we are planning to study 24 (12 phase 1 ans 12 phase 2) young people aged 10-18 years
      on insulin pump therapy. This study will involve two 7 (phase 1) and 21 (phase 2) day home
      study periods, during which glucose levels will be controlled either by an automated
      closed-loop system or by subjects usual insulin pump therapy combined with continuous glucose
      monitoring alone in random order. Prior to the closed-loop study period, there will be a
      training period in the clinical research facility, which will allow participants to
      familiarise themselves with the closed-loop system before going home.

      We aim to to determine the effect of the closed-loop computer algorithm in keeping glucose
      levels between 3.9 and 10.0 mmol/L during the daytime and overnight.
    

Detailed description: 
      The main objective of this study is to determine the efficacy, safety and utility of
      automated closed-loop glucose control in the home setting over a short term period, including
      the daytime and during the activities of normal daily living. This study builds on previous
      and on-going studies of closed-loop systems that have been performed in Cambridge in children
      and adolescents with type 1 diabetes in the clinical research facility and in the home
      setting. The data and experienced gained from this study will be utilised in planning future
      home studies.

      This is an open-label, single-centre, randomised, crossover study, involving two, 7 day
      (phase 1) and 21 day (phase 2) home study periods during which glucose levels will be
      controlled either by an automated closed-loop system or by subjects' usual insulin pump
      therapy combined with continuous glucose monitoring in random order. A total of up to 30
      children and adolescents aged 10 to 18 years with T1D on insulin pump therapy will be
      recruited through diabetes clinics, to allow for 12 completed subjects available for
      assessment in each study phase.

      Subjects will receive appropriate training by the research team on the safe use of the
      closed-loop insulin delivery system. During the training visit in a clinical research centre,
      subjects will be encouraged to mimic their usual daily activities and will be allowed to walk
      inside hospital premises. Subjects will be advised to discontinue automated closed-loop
      insulin delivery and follow their usual insulin pump therapy for certain activities such as
      periods of strenuous exercise during the 7 day (phase 1) and 21 day (phase 2) home study
      phase.

      The primary outcome is time spent in target range between 3.9 and 10.0 mmol/L as recorded by
      CGM (conservatively adjusted for potential over-estimation). Secondary outcomes are the time
      spent with glucose levels above and below target, as recorded by CGM, and other CGM-based
      metrics. Safety evaluation comprises the tabulation of severe hypoglycaemic episodes.
    

Intervention name(s): Closed-loop system; real-time CGM
Intervention type(s): Device; 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.; Subject's glucose level is controlled by usual insulin pump therapy in conjunction with real time continuous glucose monitoring (CGM)
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