Closing the Loop for 36 Hours in Adolescents With Type 1 Diabetes
Closing the Loop for 36 Hours in Adolescents With Type 1 Diabetes
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.
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.
Inclusion Criteria:

 -  The subject is between 12 and 18 years of age (inclusive)

 -  The subject has had type 1 diabetes, as defined by WHO for at least 1 year or is
 confirmed C-peptide negative

 -  The subject will have been on insulin pump for at least 3 months, with good knowledge
 of insulin self-adjustment

 -  HbA1c ≤ 12% based on analysis from central laboratory

 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, non-selective beta-blockers and MAO inhibitors

 -  Known or suspected allergy against insulin

 -  Subjects with clinical significant nephropathy, neuropathy or proliferative
 retinopathy as judged by the clinician

 -  Total daily insulin dose >= 2 IU/kg

 -  Postmenarchal girls who are pregnant or intending to become pregnant or are
 breastfeeding

 -  Any coexisting cardiac and respiratory condition (including asthma)