Algorithm to control Postprandial, Post exercise and night glucose Excursions in a portable Closed Loop format in patients after Total Pancreatectomy, 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 diabetes was tested in clnical research center
(APPEL 1 and 2) as well as at the home of the patients (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. In the APPEL 5 study the updated system was used by patient with
type 1 diabetes at home during two weeks. The system was effective and safe.
In patients after total pancreatectomy glucose control is often difficult due
to removal of the alpha and beta cells. Probably, the artificial pancreas will
improve glucose control in these patients.

The main objective of this study is to assess efficacy of the closed loop
system in patients after total pancreatectomy. Secondary objectives are to
assess the safety of the closed loop system; to determine the time that the
control algorithm is active; and to determine the glucose measurement
performance.

This is randomized cross-over trial, preceded by two patients undergoing
feasibility tests.

The intervention is one week closed loop control of blood glucose with the
miniaturized prototype after a training period of 4-6 days. 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 feasibility patients will only perform the training period.

The patients will have to wear the prototype with the subcutaneous sensors and
infusion sets. Furthermore, during the training period 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 a
wireless connection. The telemonitoring 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.