Algorithm to control Postprandial, Post exercise and night glucose Excursions in a portable closed Loop format, APPEL 4

In previous studies, we tested the feasibility of a bi-hormonal reactive closed
loop system without mealtime announcement. This system for automated control of
blood glucose in patients with type 1 diabetes was tested in the clinical
research center (APPEL 1 and 2) as well as at the home of the patients, for 48
hours (APPEL 3). Glucose control with automated closed loop control was
comparable to patient-managed open loop control. The closed loop system has
been further developed and miniaturized (from backpack to smartphone size) in
order to interfere as little as possible with daily patient life.

The main objective is to assess the efficacy of the closed loop system at the
home of the patient. Secondary objectives are to assess the safety of the new
prototype while the telemonitoring intensity is being reduced during the trial;
to investigate the use of the accelerometer incorporated in the device; to
explore whether the closed loop control improves over time; and to assess the
glucose measurement performance of the new prototype.

The study is a multicenter randomized cross-over trial.

The intervention is four days of closed loop control of blood glucose with the
miniaturized prototype. The prototype uses two subcutaneous glucose sensors,
two subcutaneous infusion sets, and incorporates two pumps and a patented
reactive closed loop algorithm. The patients will also wear a heart rate belt.
On the first morning, the patients receive training before the closed loop
system is started and they will stay one night at the clinical research center.
During the first twelve hours at home the patients are continuously monitored
with a wireless telemedicine system. Subsequently, the monitoring intensity
will be reduced, from every four hours at first to eventually once every twelve
hours. The control arm (open loop) consists of patient-managed CSII therapy and
blinded continuous glucose monitoring at home for four days.

The patients will have to wear the prototype with the subcutaneous sensors,
infusion sets and heart rate belt. Furthermore, they will be asked to keep a
diary with self-monitored blood glucose, meals and activities. During the first
day of closed loop control the patients will be admitted to the clinical
research center. There are no major risks associated with this study. Potential
risk is the administration of the incorrect amount of insulin or glucagon,
which may result in hypo- or hyperglycemia. This may be caused by failure of
the closed loop algorithm, technical failure of the system, or incorrect sensor
glucose measurements. With multiple risk control measures the risk for the
patients is minimized. The system contains a controller and a separate back up
processor and several alerts are built in the system. The patients are
monitored visually via wireless connection, both in the clinical research
center and at home. During the first day the research team, which contains at
least a medical doctor or research nurse and an engineer, is present. The
individual benefit for the participating patients is a potentially very well
regulated glucose during the test. The potential benefit from this pilot study
is however more in general; the further development of a portable closed-loop
system for automated glucose control.