Algorithm to control Postprandial, Post exercise and night glucose Excursions in a portable closed Loop format, APPEL 5

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). After the APPEL 3 study the closed loop system was
miniaturized to near smartphone format and this system was tested for 3 days at
home (APPEL 4). The results of the APPEL 4 study suggest comparable median
glucose levels for automated closed loop control and patient-managed open loop
control, but improved time in target (3.9-10 mmol/l) with closed loop control.
After APPEL 4 some improvements have been made to the miniaturized prototype to
allow patients to operate the system independently.

The main objective of this study is to assess the efficacy of the closed loop
system over an extended period. Secondary objectives are to assess the safety
of the closed loop system; to determine the time that the control algorithm is
active; to determine the glucose measurement performance; and to assess quality
of life and the treatment satisfaction for the closed loop system.

The study is a multicenter randomized cross-over trial, preceded by a limited
number of feasibility tests during which the prototype improvements are
assessed.

The intervention is two weeks 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. During 4-6 days before the intervention the
patients receive training on the use of the closed loop system and will start
using the system under close supervision. The control arm (open loop) consists
of the patient*s standard therapy (SAP or CSII) at home. The feasibility
patients will only perform the closed loop part.

The patients will have to wear the prototype with the subcutaneous sensors and
infusion sets. Furthermore, they will be asked to keep a diary with
self-monitored blood glucose, meals and activities. 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 safety processor and several alerts
are built in the system. The patients can be monitored via wireless connection.
The tele monitoring system alerts the research team in case of poor glucose
control, technical failure or unreliable sensor glucose measurements. The
individual benefit for the participating patients is a potentially very well
regulated glucose during the test. The potential benefit from this study is
however more in general; the further development of a portable closed-loop
system for automated glucose control.