SBIR Phase I: Treatment of Type 2 Diabetes through Cryoablation of the Duodenum

这项小企业创新研究阶段（SBIR） I项目是一项针对美国5-10万难治性2型糖尿病患者的新型程序性治疗。目前的治疗需要胰岛素注射和/或药物的自我管理，经常去看专家，并控制饮食。由于个体用药剂量要求、安全性和耐受性限制，患者可能无法达到最佳血糖控制。管理不善的患者可能遭受不良事件，包括心脏病发作、中风、神经损伤、失明和过早死亡。该十二指肠冷冻消融系统旨在提供一种门诊、微创手术，利用标准的、成本效益高的内镜方法对十二指肠进行控制消融。如果成功，这种新疗法将减少或消除难治性2型糖尿病患者的胰岛素和/或药物治疗。SBIR一期项目旨在开发一种新型冷冻消融系统，该系统提供高度可控和靶向的冷冻剂来冷冻十二指肠。该系统基于消融后十二指肠重塑导致葡萄糖控制和调节恢复的新证据。技术工程里程碑包括在一个独特而曲折的路径内，在极端尺寸（包括小管径和长长度）内管理低温流体的高压。一个关键的目标是生产一个系统，确保低温流体通过小直径、绝缘、长管腔输送到放置在十二指肠的一组喷雾器。第二个目标是开发一种通过喷雾器将低温流体均匀分布到目标组织的方法。最终目标是开发台架方法和测试能力，以验证一致的低温流体输送。该设计将在临床前模型中进行测试，并通过组织病理学分析评估切除组织的疗效。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This Small Business Innovation Research Phase (SBIR) I project is a novel procedural treatment for the 5-10 million people in the U.S. with medical refractory Type 2 Diabetes. Current treatments require self-management of insulin injections and/or medication, frequent visits to specialists, and a controlled diet. Patients can fail to achieve optimal glycemic control due to the individual medication dosing requirements, safety, and tolerance limits. Poorly managed patients can suffer from adverse events including heart attack, stroke, nerve damage, blindness, and early death. This Duodenal Cryoablation system aims to provide an outpatient, minimally invasive procedure for controlled ablation of the duodenum utilizing a standard, cost-effective endoscopic approach. If successful, the novel therapy will decrease or eliminate insulin and/or medical therapies in patients suffering from medical refractory Type 2 Diabetes. This SBIR Phase I project aims to develop a novel cryoablation system that delivers a highly controlled and targeted cryoablative agent for freezing the duodenum. The system is based on emerging evidence of duodenum remodeling upon ablation resulting in restoration of glucose control and regulation. The technical engineering milestones include managing high pressures of the cryogenic fluid within extreme dimensions including small luminal diameters and long length, within a unique and tortuous path. A key objective is to produce a system ensuring consistent cryogenic fluid delivery down a small diameter, insulated, long length lumen to a set of sprayers placed in the duodenum. A second objective is the development of a method of consistent cryogenic fluid distribution through the sprayers to the target tissue. The final objective is the development of bench methods and testing capabilities validating consistent cryogenic fluid delivery. The design will be tested in preclinical models and the harvested tissue evaluated via histopathological analysis for ablation efficacy.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.