Assessment of Hybrid Use of an Artificial Pancreas in a Home setting for Two Months in Patients with Type 1 Diabetes - DiAs Hybrid Home Trial

The development of a closed loop system for automated control of blood glucose
levels is underway, notably in two international study groups, the US-based iAP
study group and the EU-based AP@home consortium. Great strives have been made
towards the perfection of the control algorithm in the Clinical Research Centre
(CRC) setting. Recently studies were succesfully performed in a
hotel-environment. The next step is to perform a long term home study using a
hybrid version of the Artificial Pancreas.


| Extension 1:
On top off what is mentioned above, the next logical step is to investigate the
Artificial pancreas during up to 24h a day instead of evening and night use
only.

| Extension 2: (this amendment)
On top off investigating the artificial pancreas during up to 24h a day, the
next step would be test a new type of algorithm that has learning capabilities.

The objective is to test, validate, obtain regulatory approval for, and deploy
at home, a closed-loop Control-to-Range (CTR) system comprising two algorithmic
components: a Safety Supervision Module (SSM) and an automated Range Correction
Module (RCM).

Multi-centre randomized cross-over intervention study.

| Extension 1:
Patients currently participating in the Hybrid-AP study will be contacted for a
voluntary participation in the extension study. Each consenting patient will
undergo one extension period of 4 weeks 24-hour per day usage of the AP-system
with a voluntary pause before starting the study extension of up to 8 weeks
after finishing the Hybrid-AP study .

| Extension 2: (this amendment)
Patients currently participating in the first study extension of the Hybrid-AP
study will be contacted for a voluntary participation in the second extension
period. Each consenting patient will undergo an extension period of 4 weeks
24-hour per day usage of the AP-system using a new self learning algorithm.

This study investigates the effectiveness of the Hybrid Artificial Pancreas
(Hybrid-AP) compared to a combination of an insulinpump and glucosesensor
(OPEN) targeting adult experienced insulin pump users with T1DM.

All participants take part in a period of 2 months Hybrid-AP, a wash-out period
of 1-2 months and a periode of 2 months insulinpump glucosesensor usage (OPEN).
Based on a lottery patients will first start (cross-over) with Hybrid AP
following wash-out and OPEN or start with OPEN following wash-out and
Hybrid-AP. In the Hybrid-AP period the AP is turned on (closed loop) from
dinner to breakfast. In that period the AP will auto-regulate bloodglucose by
administering insulin using a control to range algorithm. The patient will
self-manage his diabetes using the insulin pump and glucose sensor from
breakfast to dinner just as in the OPEN period. The patient will use his
insulin pump without glucose sensor during the wash-out period.

The platform will be connected to a remote server which will anonymously
collect data (CGM values, Insulin doses, devices log). This telemedicine tool
will allow for remote monitoring by the clinical staff in case of problems
which will access the data and see glucose evolution through a secured website.
Study duration per participant will be up to 7 months containing 9 visits.

| Extension 1:
Each consenting patient will undergo one extension period of 4 weeks 24-hour
per day usage of the AP-system with a voluntary pause before starting the study
extension of up to 8 weeks after finishing the Hybrid-AP study. Total number of
visits will be 8+2=10.

| Extension 2: (this amendment)
Each consenting participant of the second extension will undergo the same
intervention as in extension one, the study period will be extended with 4
weeks and a self learning algoritm will be used. The total number of hospital
visits including this amendment counts up to 10+2=12.

The duration of the study for each patient will be up to 7 months (with 8
visits, 21 hours total). Risk to the patient includes the occurrence of
hypoglycaemia, hyperglycaemia and haematoma or infection around the blood
collection catheter sites or the insulin infusion site. The risk of hypo- and
hyperglycaemia is present in every patient with Type 1 diabetes. Research so
far suggests that closed loop glucose control is associated with less
hypoglycaemia and an increase in time-in-target. Patients will benefit from
glucosesensor usage during both the Hybrid-AP as well as the OPEN period.

| Extension 1&2: two short visits will be added to download device data and to
instruct patients' on device usage. These visits will add up to 4 hours of
participant-invested-time to the study.