SBIR-STTR Award

Development of a miniaturized single-port automated insulin delivery system utilizing a glucose sensing catheter, ultra-concentrated insulin, and an optimized control algorithm
Award last edited on: 5/21/2023

Sponsored Program
SBIR
Awarding Agency
NIH : NIDDK
Total Award Amount
$1,797,494
Award Phase
2
Solicitation Topic Code
847
Principal Investigator
Robert S Cargill

Company Information

Pacific Diabetes Technologies (AKA: PDT)

2828 SW Corbett Avenue Suite 211-A
Portland, OR 97201
   (503) 847-9170
   info@pacificdt.com
   pacificdt.com
Location: Single
Congr. District: 01
County: Multnomah

Phase I

Contract Number: 1R43DK123766-01
Start Date: 9/20/2019    Completed: 8/31/2020
Phase I year
2019
Phase I Amount
$299,555
Significance: There are over 5 million people with insulin-treated diabetes in the United States who represent a disproportionately large share of the $237B in direct medical costs attributable to diabetes. The use of continuous glucose monitoring (CGM) has been shown to reduce HbA1c levels, a proven predictor of health outcomes within this population, with the greatest improvement achieved when CGM is coupled with continuous subcutaneous insulin infusion (CSII). The recent convergence of CGM and insulin pumps has enabled the first generation of automated insulin delivery (AID) systems, promising even better glycemic control for insulin-treated diabetes. However, current AID systems are complex, cumbersome, and expensive for the patient because they require multiple devices to be worn on the body: a glucose sensor, an insulin pump, and an insulin delivery catheter. We have developed a glucose sensing catheter that reduces the number of subcutaneous components from two to one, significantly reducing the size and complexity of these systems. By integrating the sensing catheter into a patch pump, we will further simplify the system by reducing the footprint, and enabling the first fully-integrated single component AID system. Resulting reductions in system size, complexity, and cost will increase adoption rates for AID, helping improve compliance, lower HbA1c levels, and improve health outcomes among people with type 1 diabetes. Preliminary Data: We have demonstrated glucose sensing can be performed at the site of insulin delivery. However, we have discovered that there is a glucose measurement artifact that occurs immediately after dispensing liquid (insulin or saline) from the cannula, likely caused by dilution of the surrounding interstitial fluid. Preliminary data suggest the magnitude of the artifact is related to the volume of the bolus. Specific Aims: This proposal represents the first phase of an effort to integrate the dual-use cannula with a miniaturized patch pump and an AID algorithm, taking advantage of a novel concentrated insulin to reduce CGM artifact size. In Specific Aim 1, we will reduce the impact of the dilution artifact through the use of ultraconcentrated insulin. We will characterize the impact of the artifact using smaller boluses of U500 insulin in a swine study. In Specific Aim 2, we will create a calibration algorithm based on a Kalman filter and a predictive model of future sensor values to further mitigate the dilution artifact. In Specific Aim 3, we will integrate the kinetics of the U-500 insulin into a model predictive control (MPC) AID algorithm developed by Oregon Health & Science University (OHSU) and optimize the algorithm to (1) incorporate a model of the kinetics of the Thermalin insulin and (2) eliminate any remaining dilution artifact that may still be present. We will evaluate the performance of the new calibration algorithm on the data collected in Aim 1 as well is in other human data that we have collected with the glucose sensing catheter. The MPC algorithm will be evaluated in silico using the OHSU virtual patient population in preparation for full integration into the Thermalin StampPump in phase 2 of this proposal. In summary, this collaborative effort between PDT, OHSU, and Thermalin brings together the only published amperometric glucose sensing catheter with a fault-tolerant AID algorithm and the only rapid, concentrated insulin. In short, we are the only team currently capable of providing this novel solution for a unified automated insulin delivery device.

Public Health Relevance Statement:
NARRATIVE In this project, a combined insulin delivering and continuous glucose monitoring (CGM) cannula will be integrated with a miniaturized patch pump from Thermalin and an automated insulin dosing (AID) algorithm from Oregon Health & Science University. In Phase 1, CGM performance will be improved through use of ultra- concentrated insulin from Thermalin to reduce bolus size and through the use of predictive algorithms that are optimized to accommodate a dilution artifact following large boluses. An AID algorithm will be updated to work with Thermalin U-500 insulin and optimized to eliminate the impact of any remaining dilution artifact.

Project Terms:
Adoption; Algorithms; base; Blood Glucose; blood glucose regulation; Bolus Infusion; Calibration; Cannulas; Carbohydrates; Catheters; Complex; Computer Simulation; cost; Coupled; Data; design; Development; Devices; Diabetes Mellitus; Dose; Drug Kinetics; Event; Family suidae; Future; Generations; Glucose; glucose monitor; glucose sensor; glycemic control; Glycosylated hemoglobin A; Health; Health Sciences; Hour; Human; human data; Hypoglycemia; improved; Infusion procedures; Insulin; Insulin Infusion Systems; Insulin-Dependent Diabetes Mellitus; Intercellular Fluid; Kinetics; Liquid substance; Measurement; Measures; Medical Care Costs; Miniature Swine; miniaturize; Modeling; Morphologic artifacts; novel; Oregon; Outcome; Outcome Measure; patient population; Patients; Performance; Phase; physical model; Physiological; Plasma; Population; prediction algorithm; predictive modeling; Preparation; primary outcome; Publishing; Pump; Reading; Reporting; Saline; sensor; Site; Standard Model; subcutaneous; System; Time; Translating; United States; Universities; Update; virtual; Work

Phase II

Contract Number: 2R44DK123766-02
Start Date: 9/20/2019    Completed: 6/30/2023
Phase II year
2021
(last award dollars: 2022)
Phase II Amount
$1,497,939

Significance: There are over 5 million people with insulin-treated diabetes in the United States who representa disproportionately large share of the $237B in direct medical costs attributable to diabetes. The use ofcontinuous glucose monitoring (CGM) has been shown to reduce HbA1c levels, a proven predictor of healthoutcomes within this population, with the greatest improvement achieved when CGM is coupled withcontinuous subcutaneous insulin infusion (CSII). The recent convergence of CGM and insulin pumps hasenabled the first generation of automated insulin delivery (AID) systems, promising even better glycemiccontrol for insulin-treated diabetes. However, current AID systems are complex, cumbersome, and expensivefor the patient because they require multiple devices to be worn on the body: a glucose sensor, an insulinpump, and an insulin delivery catheter. We have developed a glucose sensing catheter that reduces thenumber of subcutaneous components from two to one, significantly reducing the size and complexity of thesesystems. The PDT interoperable sensing cannula assembly that we are proposing to commercialize in thisphase 2 SBIR will allow any insulin patch pump manufacturer to rapidly integrate CGM directly on the insulindelivery cannula, thereby enabling people with T1D who are patch pump users to effortlessly utilize CGMthrough a single subcutaneous injection site. Importantly, this platform will also improve AID system reliabilityand security by replacing the wireless communication from CGM to pump controller with a direct wiredconnection. Resulting reductions in system size, complexity, and cost will increase adoption rates for pumpuser and people using AID, helping improve compliance, lower HbA1c levels, and improve health outcomesamong people with type 1 diabetes. Preliminary Data: PDT has recently demonstrated that delivering insulinat the site of glucose sensing is possible using a patented redox mediator-based sensing cannula. However,we have also shown that there is a dilution artifact that occurs immediately after a dose of insulin is deliveredthrough the cannula. We have shown that this artifact is independent of whether insulin or saline is delivered.In Phase 1 of this SBIR, we demonstrated in a swine study that this artifact is related to the size of the bolus.We further demonstrated that the artifact can be significantly reduced by using higher concentration insulin andultimately eliminated by using sophisticated predictive signal processing methods. Specific Aims: In Phase 2of this project, we will use the products of Phase 1 to take the next logical steps in integration of our sensingcannula into a dual function patch pump platform. In Specific Aim 1, we will further characterize and evaluatethe accuracy of the PDT sensing cannula in a human study. In Specific Aim 2, we will work with a commercialpump partner (EOFlow) to develop and evaluate an interoperable sensing cannula assembly (ISCA) that isdesigned for rapid integration into a patch pump. The ISCA will include the required electronics, mechanicalcomponents, and a software development kit that will enable rapid integration into commercial patch pumps.Working with our academic partners at OHSU, we will transfer the artifact elimination predictive signalprocessing algorithm and port this algorithm to the ISCA for use in real-time operation. In Specific Aim 3, wewill integrate the sensor assembly into our commercial partner's patch pump and validate the performance andaccuracy of the design in a swine study. At the conclusion of Phase 2, we will have a dual-function glucose-sensing patch pump validated in a swine study and poised to enter clinical study. In Phase 2B, we will conductthose studies, and work with our academic collaborators and commercialization partners to incorporate amodel predictive controller into the patch pump to yield an all-in-one automated insulin delivery solution.

Public Health Relevance Statement:
Narrative Automated insulin delivery has the potential to improve glucose control and reduce negative health outcomes associated with poor glucose control. However, the complexity of current automated insulin delivery systems is currently high requiring people using the system to inject multiple devices into their body. In this phase 2 proposal, we will work to commercialize an interoperable glucose sensing cannula module that can be used to integrate continuous glucose monitoring into any patch pump, thereby reducing the number of required system components injected into the patient's body from two to one.

Project Terms:
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