Small Business Innovation Research (SBIR) to Develop New or Improved Closed Loop Automated Technologies for Diabetes Therapy and Monitoring (R43/R44)

Type 1 diabetes (T1D) results from the autoimmune destruction of the insulin-producing cells of the pancreatic islets of Langerhans and affects more than one million Americans, usually with onset in childhood or young adulthood. The disease markedly impairs quality of life and shortens lifespan primarily through premature mortality.  T1D is associated with numerous complications including blindness, renal failure, painful nerve disorders, and amputation.  In addition to its devastating toll in human suffering, T1D and its complications result in significant health care expenditures for families and constitute a major societal economic burden.

Clinical Trials have demonstrated significant reductions in complications of T1D through intensive control of blood glucose levels.  However, despite the availability of increasingly effective treatment modalities, including insulin analogues, continuous glucose monitors (CGMs) and continuous subcutaneous insulin infusion (CSII) devices, a substantial proportion of patients with T1D cannot achieve optimal glycemic control despite enormous efforts.  Compounding this difficulty is the trade-off between improved glycemic control and an increased risk for potentially life-threatening hypoglycemia.

A viable option for the treatment of diabetes is a system (artificial pancreas or closed-loop) that can mimic normal pancreatic beta cell function thereby restoring normal metabolic homeostasis without causing hypoglycemia.  However, there are important technological obstacles such as glucose-sensing inaccuracies, imperfect algorithms for calculating the appropriate dose of insulin/glucagon taking into consideration diet and physical activity, insulin pumps’ mechanical problems, time delay from subcutaneous insulin infusion to pharmacologic effect, biocompatibility issues and data transmission, inter-device communication deficiencies that need to be resolved through the development of new technologies that may lead to integrated/automated devices.  The ultimate research goal would be the development of mechanical or bio-artificial systems that may improve metabolic control and decrease glycemic excursions robustly preventing hypoglycemic episodes.

This FOA is intended to support cutting edge research conducted by small business leading to the development of innovative technologies that may advance progress toward an integrated, long term, automated, wearable, glucose regulated insulin/pancreatic hormone delivery closed loop system.  This announcement has two main purposes: a) promote technical innovation and b) pre-clinical or clinical testing of single or combined components of a closed loop system.  Examples of projects that this announcement intends to attract include but are not limited to:

1. Glucose sensors and pancreatic hormones delivery systems:

• Development of novel and more accurate non-enzymatic based glucose detection technologies.
• Development of new miniaturized, implantable or minimally invasive continuous glucose sensors with long functional life (at least 4 weeks), real time measurement, with no or minimal need of recalibration, easily implanted and replaced, unobtrusive to the user and accurate at low glycemic levels.
• Development of redundant continuous glucose monitoring technologies that may provide sufficient data to allow automated hormone delivery to target euglycemia with minimal risk for overdose
• Application of nanotechnology advances to the design of new glucose sensing and insulin delivery devices.
•  Development of miniaturized multisensor platforms able to detect glucose and other metabolically relevant analytes. For instance, integration of insulin sensors to a closed loop platform.
• Development of novel biocompatible smart biomaterials to be used for the manufacturing of implantable devices.
• Development of implantable biohybrids matrices/membranes that may release bioactive agents which either promote vascularization and/or inhibit the inflammatory/fibrotic response allowing higher biocompatibility and longer durability of devices.
• Development of injectable/implantable glucose regulated insulin/glucagon delivery systems/depots able to function in a homeostatic fashion lasting days/weeks.
• Development of highly concentrated and stable insulin formulations that are more rapidly absorbed for closed loop insulin delivery.
• Novel and more stable glucagon formulations that could be used in a closed loop system.
• New, more advanced insulin/glucagon delivery devices/pumps, external or implantable able to be integrated in a closed loop system.  For instance:  Dual chamber pumps for multi hormonal therapy.
• Smarter pump technologies - pumps that directly or indirectly monitor and track insulin delivered for use with Algorithms.

2. Algorithms and Integrated Systems:

• Development of reliable and integrated algorithms that translate accurate glucose measurements into changes in the delivery of pancreatic hormones in order to maintain glucose excursions within the physiological range and that are able to detect/correct failure of the closed loop system components.
• Development of more effective, reliable and integrated wireless/inter-device communication systems.
• Development of smaller and portable controllers.
• Technologies that improve or facilitate information visualization and integration of data for analysis and more efficient/user friendly self-management.
• Development of optimized hypoglycemia alert and insulin suspension systems.
• Closed loop systems using algorithms that may incorporate delivery of counter-regulatory hormones in order to prevent or correct hypoglycemia effectively.
• Development of remote monitoring systems to optimize performance of the integrated platforms
• Development of new devices able to integrate the sensing, controller and delivery components in one unit.
• Development and/or optimization of bioartificial pancreas/islet replacement devices and its components.

3. Pre-Clinical and Clinical Topics:

• Development and testing of new technologies for visually and/or cognitively impaired patients with diabetes.
• In-silico simulation models that may facilitate the design of proper clinical studies to test new devices.
•  Pre-clinical testing of components of a closed loop system.
•  Clinical testing of components of a closed loop system.