? DESCRIPTION (provided by applicant): Clinical Acceptance of the Artificial Pancreas: the International Diabetes Closed Loop (iDCL) Trial In 2009 we put forward the idea that the artificial pancreas (AP) is not a single-function all-in-one device but a network encompassing the patient in a digital treatment ecosystem that can offer different treatment modalities tailored to patient preferences and signal availability. We implemented this idea in the Diabetes Assistant - DiAs - the first AP smart phone suitable for everyday use. After extensive DiAs testing in the U.S. and Europe, we can confirm that reliable technology has been developed and sufficient data have been accumulated to warrant a large-scale study aiming to establish the AP as a clinically accepted treatment for type 1 diabetes. To do so, we propose a multi-center project involving research sites in Virginia, California, New York, Minnesota, Colorado, Florida, Italy, France and Holland, all with extensive AP track record. We will execute two trials: Study 1 - the International Diabetes Closed Loop Trial - will enroll 240 patients with type 1 diabetes to test the safety and efficacy of Control-to-Range (CTR) vs. Sensor-Augmented Pump (SAP). We hypothesize that: SA1: CTR, compared to SAP, will result in: (1) Improved HbA1c without increased incidence of hypoglycemia for those with HbA1c?7.5%; (2) Lower incidence of hypoglycemia without deterioration in HbA1c for those with HbA1c<7.5%; (3) Improved time within the glucose target ranges of 70-180mg/dl during the day and 70- 140mg/dl overnight, and (4) Fewer episodes of severe hypoglycemia, DKA, and other serious adverse events. SA2: Use of DiAs will result in: (1) Reduced fear of hypoglycemia and better quality of life as compared to SAP; (2) System acceptance and positive evaluation of the DiAs graphical user interface and remote monitoring/ automated notification system - the latter will be particularly useful for parents of children with diabetes, and (3) System reliability and usability estimates meeting regulatory acceptance criteria. Study 2 - the Enhanced Control-to-Range Trial - will follow 180 patients who complete Study 1 for additional 6 months to test the incremental effect of enhanced CTR using a next-generation adaptive control algorithm that builds on the well-studied and clinically tested zone model-predictive control strategy. We hypothesize that: SA3: treatment escalation will preserve the glycemic and behavioral benefits of CTR attained in Study 1 and will result in: (1) further improvement in glycemic control, including increased time within glucose target range (70-180mg/dl) during the day, primarily due to improved meal control and lower postprandial blood glucose variability, and (2) further reduced HbA1c for those who did not achieve the target of HbA1c <7.5% on CTR. Our broad objective is to test and validate a multicomponent AP system that can, as required by the NIH program announcement ...satisfy safety and efficacy requirements by regulatory agencies regarding the clinical testing of AP device systems. We will establish that contemporary smart phones provide accessible and user-friendly AP platform that is acceptable by regulatory agencies, facilitates technology proliferation, and gives physicians and patients the freedom to select an optimal treatment for any person, at any particular time.

UC4DK108483

2016-01-01

2019-12-31