Research Project
9183633
PROJECT SUMMARY / ABSTRACT Over 400,000 US patients on continuous subcutaneous insulin infusion (CSII) pump therapy are required to change their infusion site every 2?3 days. Many patients attempt to use their infusion catheters for longer durations, resulting in poorer blood glucose control after day 3 of site use and an increased risk for hyperglycemia due to infusion failure. Unfortunately, insulin absorption by the surrounding subcutaneous tissue varies from day-to-day and dose-to-dose and may become temporarily or permanently impaired on any day of catheter use. We aim to develop an optimized CSII catheter that will allow for more consistent and reliable insulin absorption (pharmacokinetics or PK) with rapid on and rapid off actions (pharmacodynamics or PD). More predictable and consistent insulin absorption will enable patients to achieve improved blood glucose control with longer use of each infusion site. We hypothesize that a CSII catheter with multiple orifices along the catheter's shaft will deliver insulin into the subcutaneous tissue in a cylinder-shape, providing a much larger surface area than the flattened sphere shape of insulin depots produced by conventional, single-orifice catheters. The larger surface area accesses more capillary and lymph vessels, allowing for more rapid and uniform insulin uptake into the circulation. Furthermore, the catheter's design and insertion method will reduce tissue trauma and inflammation. Minimizing tissue damage and the immune response will further reduce insulin absorption variability. Success of this feasibility study will support further development of multiple-orifice CSII catheters made of both steel and soft polymers (e.g. Teflon) with automated insertion methods. In this SBIR Phase 1 study, we will construct prototype CSII catheters by laser drilling holes into a small diameter stainless steel spinal needle with an atraumatic pencil-point tip. The performance of this prototype catheter will be compared to a commercial catheter in a study of 6 swine for 7 days. We will evaluate the flow of insulin through the prototype catheter's holes into the adjacent vascular tissue using micro-CT imaging with an insulin/x-ray contrast agent, histology of tissue stained for insulin, and glucose-clamp insulin PK-PD studies. The histology data and the micro-CT imaging data will be used to correlate the distribution of insulin within the subcutaneous tissue (3D shape, volume, and surface area) with the PK-PD actions of a insulin lispro bolus. This pilot animal data will demonstrate how well the device distributes insulin to a larger volume of tissue and reduces tissue trauma. Subsequent SBIR Phase 2 funding will support human studies demonstrating the improved efficacy of insulin absorption.
