Closing the Loop for 36 Hours in Adolescents With Type 1 Diabetes
Condition: Type 1 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 2

Summary: 
      High variability of blood sugar levels and high incidence of night-time hypoglycaemia (low
      blood sugar) in young people with type 1 diabetes (T1D) make achieving the treatment goals in
      this population extremely challenging.

      Our ongoing research focuses on the development of a closed-loop glucose control in children
      and adolescents with T1D. The three components of the closed-loop system are a continuous
      glucose monitor, an insulin pump, and a computer-based algorithm. The studies performed thus
      far evaluated the efficacy and safety of overnight closed-loop glucose control. The results
      showed that overnight closed-loop improved control of blood glucose and prevented nocturnal
      hypoglycaemia, as compared to the conventional insulin pump therapy. The next objective is to
      evaluate the efficacy and safety of closed-loop insulin delivery over a prolonged time
      period, including the daytime, when normal living activities occur. This will pave the way
      for a more comprehensive use of closed loop systems to control glucose levels in T1D.

      The present study adopts an open-label, randomised, 2-period cross-over design whereby the
      safety and efficacy of closed-loop insulin therapy will be compared with the conventional
      insulin pump therapy in 12 adolescents with T1D. Participants aged 12 to 18 years will be
      randomised for two 36 hour studies in a clinical research facility, during which glucose
      levels will be controlled by either the computer-based closed-loop algorithm (intervention
      arm) or by conventional insulin pump therapy (control arm). During both studies participants
      will perform normal daily activities, i.e. playing, reading, snacking and physical activity.
      On both occasions, the Actiheart, a combined heart rate and movement sensor will be used to
      accurately quantify each subject's individual physical activity energy expenditure during the
      36 hour study period and for 36 hours of free living during weekday.
    

Detailed description: 
      The study is an open-label, randomised, 2-period crossover study comparing the closed-loop
      insulin therapy with the conventional insulin pump therapy in 12 adolescents with type 1
      diabetes.

      Subjects who consented to take part in the study will attend the Clinical Research Facility
      on two occasions, each lasting 36 hours. Approximately 1-3 days prior to each Study Visit, a
      subcutaneous continuous glucose monitoring (CGM) device will be inserted.

      On each Study Visit subjects will arrive between 17:30 and 18:00 and will stay in the
      clinical research facility for two nights.

      Shortly after arrival the subjects will have Actiheart monitor fitted and a cannula inserted
      into a vein of one arm for blood sampling purposes. Blood sampling for plasma glucose and
      plasma insulin will start at 18:30 and will be carried out at 30 minutes intervals during the
      day and at 60min intervals during the night throughout the study period. Plasma glucose
      measurements will be done in real time every 30min during the day and every 60min during the
      night except when when plasma glucose < 3.5mmol/L or following treatment for hypoglycaemia,
      when the measurements will be carried out every 15 minutes.

      On Study Visit 1 the subjects will be randomised on arrival to receive either the
      conventional insulin pump therapy or the closed-loop intervention. At 18:30 subjects will
      perform 5 to 10 minutes exercise on a bicycle to determine the settings needed to achieve a
      heart rate of 140 bpm corresponding to an exercise level at 55%60% of peak VO2. In the
      closed-loop intervention arm the insulin pump therapy will be driven by the computer-based
      algorithm from 19:30 until the end of the study. The basal insulin infusion rate on the
      insulin pump will be adjusted manually at 15min intervals following the computer-based
      algorithm advice. During the control arm, the subject will carry on with their usual insulin
      pump regimen. In both groups CGM will be continued throughout the whole of the study period.
      Subjects who completed Study Visit 1 will cross over to the alternative Study Visit schedule
      after an interval of 1 to 6 weeks.
    

Intervention name(s): Closed-loop insulin delivery; Standard insulin pump treatment
Intervention type(s): Other; Other
Intervention description(s): Basal subcutaneous insulin delivery to be adjusted at 15min cycles according to the computer-based algorithm advice.; Subcutaneous insulin delivery to be performed based on subjects' standard treatment
Intervention MeSH terms: Insulin; Insulin, Globin Zinc
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Closed-loop systems; day-and-night glucose control