Support for Small Business Innovation Research to Develop New Open and Closed-Loop Automated Technologies for Better Type 1 Diabetes Therapy and Monitoring (SBIR) (R43/R44- Clinical Trial Not Allowed)

Purpose and Research Objectives

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 type 1 diabetes (T1D) cannot achieve adequate glycemic control and avoid acute complications such as hypoglycemia.  NIDDK has long supported this area of research, especially through small business projects, and this support has contributed substantially to the development of new devices that are increasingly used in clinical practice.  Nonetheless, the approved devices and current technologies still have significant limitations, and it is important to put renewed emphasis on the creation of the next generation of devices that will further the goals of relieving patients of the burden of diabetes self-management and achieving daily euglycemia to prevent acute and chronic complications.  Several relevant projects have been supported because of the release of similar FOAs in the recent past. However, given the pace of technical progress in this field and the substantial room for improvement in reliability, accuracy, and patient burden of current devices, NIDDK considers it important to continue supporting research in this field.

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, wearable/implantable, glucose regulated open and closed loop insulin/pancreatic hormone delivery systems.  This announcement has two main purposes: a) promote technical innovation and b) pre-clinical testing of single or combined components of open and closed loop systems.  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 (sc or ip) or minimally invasive continuous glucose sensors with long functional life (at least 4 weeks), real time measurement, no or minimal need of recalibration, easily implanted and replaced, unobtrusive to the user and accurate at low glycemic levels (<54 mg/dl).
• 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.
• 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 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.
• Development of injectable/implantable glucose regulated insulin/glucagon delivery systems/depots able to function in a homeostatic fashion lasting days/weeks.

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, including personalized digital insulin dosing decision support systems for non-insulin pump delivery.
• 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.

3. Pre-Clinical Topics:

• In-silico simulation models that may facilitate the design of proper clinical studies to test new devices.
• Pre-clinical testing of components of an open or closed loop system.

Note: If your study is designed only to evaluate the functionality of your technology or device (e.g., ability to accurately measure glucose), your study would not be considered a clinical trial. However, if you are testing the ability of your device to improve glycemic control or prevent hypoglycemia in individuals, this would be a clinical trial. Further information about the NIH definition of a clinical trial is available on the NIH website ( https://grants.nih.gov/policy/clinical-trials.htm), including illustrative cases studies (https://grants.nih.gov/policy/clinical-trials/case-studies.htm). If a clinical trial in this field is planned, it should be submitted in response to this FOA:    https://grants.nih.gov/grants/guide/pa-files/PAR-17-034.html.  

See Section VIII. Other Information for award authorities and regulations.