FrostBite-DMR - A New Drug-Free Approach for Treating Type 2 Diabetes

FrostBite-DMR——一种治疗 2 型糖尿病的无药物新方法

• 批准号: 10596881
• 负责人: John M BAUST
• 金额: $ 29.83万
• 依托单位: CELL PRESERVATION SERVICES, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-22 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10596881
• 关键词: Ablation; Acute Renal Failure with Renal Papillary Necrosis; Address; Adverse event; Agonist; Allergic Reaction; Animals; Arrhythmia; Back; Biliary; Biomedical Engineering; Biotechnology; Body Weight decreased; Businesses; Cardiac; Cardiovascular system; Catheters; Cells; Clinical Research; Clinical Trials; Communities; Consequentialism; Cryopreserved Cell; Cryosurgery; Development; Devices; Diabetic Retinopathy; Disease; Disease model; Dose; Drug Side Effects; Duodenum; Endoscopes; Esophagus; Failure; Freezing; Frostbite; GLP-I receptor; Gallbladder; Headache; Hemorrhage; Hepatic; Human Resources; Hyperglycemia; Hypoglycemia; Incidence; Insulin; Insulin-Dependent Diabetes Mellitus; Kidney; Knowledge; Licensing; Life; Liver; Malignant neoplasm of pancreas; Malignant neoplasm of thyroid; Measures; Medical; Medical Device; Metformin; Methods; Modality; Molecular; Molecular Biology; Mucous Membrane; Muscle; Necrosis; Nitrogen; Non-Insulin-Dependent Diabetes Mellitus; Operative Surgical Procedures; Outcome; Pancreas; Pancreatitis; Patients; Persons; Pharmaceutical Preparations; Pharmacotherapy; Phase; Postoperative Period; Production; Prostate; Publishing; Radiofrequency Interstitial Ablation; Reporting; Risk; Safety; Serous Membrane; Small Intestines; Surface; System; Taste Perception; Technology; Temperature; Testing; Thermal Ablation Therapy; Time; Tissues; Water; alternative treatment; bariatric surgery; base; commercialization; comparative efficacy; design; effective therapy; efficacy testing; first-in-human; flexibility; gastrointestinal; improved; in vivo Model; in vivo evaluation; indexing; infancy; inhibitor; instrument; interest; medical schools; microwave electromagnetic radiation; non-compliance; novel strategies; novel therapeutics; preservation; pressure; response; side effect; success; tumor

Type 2 diabetes mellitus (T2D) is increasing in incidence throughout the world with nearly 552 million people who may be afflicted with this disease by 2030. There are now over 50 different drugs that can be used to treat T2D but about half of patients do not respond well to these agents and their hyperglycemic condition remains a life-threatening problem. Indeed, the first line drugs such as Metformin, GLP-1 receptor agonists (e.g. Semaglutide), DPP-4 inhibitors, SGLT2 inhibitors and others have documented side effects that include hypoglycemia, gastrointestinal side effects, pancreatitis, pancreatic cancer, thyroid cancer, gallbladder issues, cardiovascular changes, acute kidney injury, diabetic retinopathy, allergic reactions, increase in biliary disease, change in taste and headaches. As an alternative to these drugs, the first in human report was published in 2016 showing that duodenal mucosal resurfacing (DMR) of T2D patients could improve their hyperglycemic conditions as well as several hepatic indices without having to use these front line drugs. This study was initiated, in part, because of the well documented and surprising observation that bariatric surgery also resulted in a similar benefit to T2D patients that was independent of consequential weight loss. Since 2016 several clinical studies have been conducted on DMR and all showed benefit to patients with T2D who weren’t responding to traditional medical treatments or who were non- compliant with medications. While promising, DMR has been reported to have a high rate of technical failure due to catheter malfunctioning suggesting that improvements in the technical-functional aspects of current devices need to be addressed. Furthermore, one such DMR device that has shown benefit in several clinical trials uses hydrothermic ablation (hot water at 80 to 90°C) to achieve DMR. Like radiofrequency ablation, HiFU, microwave and other heat ablation technologies used to target and ablate tumors and treat cardiac arrhythmias, the passive spread of heat can’t be easily controlled and has shown to result in collateral tissue damage such as muscular segmental necrosis and serosa bleeding with postoperative adverse events from DMR hydrothermic ablation reported to be an issue with 64% of the cases. CPSI Biotech intends to capitalize on this emerging DMR market that is currently in its infancy and develop an improved DMR thermal ablation probe that uses freezing (cryoablation) rather than heat for duodenal resurfacing. The advantages of the proposed FrostBite- DMR cryoballoon include (a) freezing is self-limiting in contrast to heat and presents less opportunity for collateral damage to adjacent deeper duodenal tissue; (b) cryoablation has been shown to be more effective, safer and have fewer complications than heat based ablation in numerous tissues including cardiac, esophageal, renal, prostate and pancreatic among others; (c) CPSI’s PSN cryoablation systems can generate and deliver ablative temperatures faster and colder than any other known cryoablation systems currently on the market thus decreasing procedural time and, as such, will offer improved versatility and safety compared to current technologies. The Specific Aims of this project are the following: (SA1) Determine the thermal ablative dose of duodenum cells subjected to cryoablation; (SA2) Develop FrostBite-DMR™, a flexible endoscope compatible cryoballoon, and (SA3) Test the efficacy of FrostBite in ex vivo and in vivo models. The overall intent of the project is to capitalize on the documented success of DMR published in the last few years as well as CPSI’s expertise in developing improved cryoablation catheters so that an improved DMR ablation device can be developed that is safer, more efficient, and can be better operator controlled leading to more successful DMR for T2D patients who do not respond well to current T2D drug treatments.

2型糖尿病（T2D）在全球发病率增加，近5.52亿 可能到2030年可能患有这种疾病的人。现在有50多种不同的药物可以 用于治疗T2D，但大约一半的患者对这些药物及其响应不佳 高血糖状况仍然是威胁生命的问题。确实，第一行毒品，例如 二甲双胍，GLP-1受体激动剂（例如，半卢宾），DPP-4抑制剂，SGLT2抑制剂和 其他人则记录了包括低血糖，胃肠道副作用的副作用， 胰腺炎，胰腺癌，甲状腺癌，胆囊问题，心血管变化，急性 肾脏损伤，糖尿病性视网膜病，过敏反应，胆道疾病的增加，口味变化和 头痛。作为这些药物的替代方法，人类报告中的第一份是在2016年发布的 T2D患者的十二指肠粘膜重塑（DMR）可以改善其高血糖 条件以及几个肝脏指数，而不必使用这些前线药物。这项研究 部分原因是有据可查，令人惊讶的是减肥 手术还与T2D患者产生了类似的好处，而与后果无关 减肥。自2016年以来，已经对DMR进行了几项临床研究，均显示出益处 对于没有反应传统药物或非反应的T2D患者 符合药物。据报道，虽然有希望的DMR具有很高的技术率 由于导管故障导致的故障，表明技术功能的改进 需要解决当前设备的各个方面。此外，已经显示的一种DMR设备 在几项临床试验中，有益于水热消融（80至90°C时的热水）实现DMR。 像射频消融一样，HIFU，微波炉和其他用于靶向的热消融技术 和灌溉肿瘤并治疗心律不齐，热的被动传播无法轻易控制 并显示会导致附带组织损伤，例如肌肉节段坏死和浆膜 据报道，DMR水热消融中的术后广告活动据报道是一个问题 有64％的案件。 CPSI Biotech打算利用这个新兴的DMR市场 目前处于起步阶段，并开发了使用冻结的改进的DMR热消融探针 （冷冻）而不是加热十二指肠重铺。拟议的冻伤的优势 DMR Cryoballoon包括（a）冻结是自限制的，与热量相反，机会更少 为了对相邻深层组织的附带损害； （b）已证明冷冻化是 比许多组织中的基于热的消融更有效，更安全，并发症较少 包括心脏，食管，肾脏，前列腺和胰腺等； （c）CPSI的PSN 冷冻系统可以比其他任何人都更快，更冷 当前市场上已知的冷冻系统，因此减少了程序时间，因此 与当前技术相比，将提供改善的多功能性和安全性。这个特定的目的 项目如下：（sa1）确定约十二指肠细胞的热消融剂量 冷冻; （SA2）开发Frostbite-DMR™，一种灵活的内窥镜兼容的Cyroballoon，并且 （SA3）测试在体内和体内模型中冻伤的效率。该项目的总体意图是 利用过去几年发表的DMR的记录成功的成功以及CPSI的 开发改进的冷冻导管的专业知识，以便改进的DMR消融设备 可以开发安全，更高效的人，并且可以成为更好的操作员，从而导致更多 对当前T2D药物治疗反应不佳的T2D患者的成功DMR。