DESCRIPTION (provided by applicant): We have built and extensively tested our bihormonal bionic pancreas (BP) in inpatient and real-world outpatient studies in subjects with type 1 diabetes (T1D). Through an eight-year collaboration between Boston University (BU) and the Massachusetts General Hospital (MGH), we have completed three 1- and 2-day inpatient studies testing a laptop version of the BP and three 5-day outpatient studies testing an iPhone version of the BP in adults with T1D (in downtown Boston), adolescents with T1D (in a diabetes camp), and pre-adolescents with T1D (in a diabetes camp). In collaboration among BU, MGH, the University of Massachusetts Medical Center, Stanford University, and the University of North Carolina, Chapel Hill, we completed an 11-day Bionic Pancreas Multi-Center outpatient study in adults with T1D testing the iPhone version of the BP at home and in the workplace without restrictions on activity or exercise. We have recently built a new bihormonal BP device platform in accordance with Class III medical device standards that integrates a microprecision dual-infusion pump that (1) separately delivers insulin and glucagon, (2) acts as a receiver for an FDA-cleared continuous glucose monitor (CGM), and (3) includes our clinically tested suite of mathematical control algorithms that autonomously determines and commands doses of insulin and glucagon based on CGM glucose data. This new device platform provides a turnkey solution that will standardize, simplify, and improve T1D therapy. Here we propose to conduct the Bionic Pancreas Pivotal Trial (BPPT), which will enroll 480 children and adults with T1D (ages 8 and older, HbA1c <11%) to test and qualify the fully integrated version of the BP and to provide all of the clinical data necessary for a pre-market approval (PMA) application to the FDA. We propose to achieve this objective with the following specific aims: (1) to evaluate the usability of the BP in a human factors study, to refine the device and user interface, if necessary, based on the study results, and to qualify its functionality in a small outpatient feasibility study (the Bionic Pancreas Bridging Study); and (2) to conduct the BPPT to test the safety and efficacy of the final BP system in controlling glycemia (with co-primary outcomes of HbA1c and percentage of CGM glucose measurements < 60 mg/dl), to evaluate the behavioral and psychosocial impact of our technology relative to usual care, and to provide data on the safety of chronic glucagon administration sufficient for a new use indication for this device.

PUBLIC HEALTH RELEVANCE: Good, consistent management of blood sugar levels in people with type 1 diabetes is essential to preventing and minimizing health complications. Our goal is to conduct the final (pivotal) clinical trial to test a new fully integrated and wearable bionic pancreas medical device that will automatically manage blood sugar levels in people with type 1 diabetes and thus reduce the burden of diabetes care; this trial will provide all clinical results needed to submit a pre-market approval application to the US FDA. The study will comprehensively test the hypothesis that our bionic pancreas device, which integrates (1) a glucose-sensing device that automatically and frequently estimates blood sugar levels, (2) decision software that automatically determines therapeutic dosing requirements, and (3) a dual-infusion system that automatically delivers insulin to lower blood sugar levels and glucagon to raise blood sugar levels, will provide effective and safe management of blood sugar levels in people with type 1 diabetes and, as a consequence, will dramatically reduce the risk of health complications that often arise with type 1 diabetes.