Photodynamic Therapy to Prevent Arteriovenous Fistula Maturation Failure

光动力疗法预防动静脉内瘘成熟失败

基本信息

批准号：
9918649
负责人：
PRABIR ROY-CHAUDHURY
金额：
$ 22.5万
依托单位：
ADGERO BIOPHARMACEUTICALS HOLDINGS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-17 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9918649
关键词：
Address Anatomy Aneurysm Animals Area Arteriovenous fistula Balloon Angioplasty Bilateral Biological Biology Blood Vessels Blood flow Caliber Cardiovascular Models Caring Catheters Clinical Clinical Research Contralateral Development Dialysis procedure Disease Dose End stage renal failure Endothelium Expenditure Extravasation Failure Family suidae Feasibility Studies Financial cost Fistula Forearm Healthcare Systems Hemodialysis Hemorrhage Histologic Hyperplasia Infection Inflammation Inguinal region Injury Innovative Therapy Joints Lead Light Maintenance Medical Medicine Microscopic Modeling Morbidity - disease rate Myofibroblast Names Necrosis Operative Surgical Procedures Outcome PUVA Photochemotherapy Patients Pharmaceutical Preparations Phase Photosensitization Photosensitizing Agents Placebos Play Pre-Clinical Model Procedures Process Research Risk Safety Short Waves Signal Transduction Singlet Oxygen Site Smooth Muscle Myocytes Stenosis Stents Technology Testing Thrombosis Time Toxic effect Treatment Efficacy Venous cell type commercialization cost drug development economic cost effective therapy experience hemodynamics improved infection risk innovation innovative technologies macrophage mortality novel pre-clinical research prevent response success systemic toxicity vascular injury

项目摘要

Project Summary - Photodynamic Therapy to Prevent Arterio-Venous Fistula Maturation Failure: An Unmet Clinical Need Establishing and maintaining arteriovenous (AV) access sites is critical for patients on hemodialysis. The most preferred AV access is the forearm fistula which is now used for the majority of hemodialysis patients. However, a common problem with AV fistulas is primary maturation failure, i.e. following surgical placement, their fistulas do not become viable for dialysis without additional percutaneous or surgical interventions and some never become viable. This failure can lead to increased morbidity from prolonged use of central venous catheters and results in a large financial cost to the health care system. This is particularly frustrating because it is well established that a mature fistula provides the hemodialysis patient with the most effective means of AV access. While the exact mechanisms of maturation failure are not fully understood, it is generally accepted that post-surgical neointimal hyperplasia and inadequate venous remodeling play key roles and preventing either of these processes should substantially improve AV fistula outcomes. This project will investigate the potential for a particular form of photodynamic therapy to improve fistula maturation rates. Preliminary studies in related cardiovascular models indicate this therapy could substantially impact the main failure mechanisms involved in fistula maturation failure. From a commercialization perspective, this therapy also has the advantage that is already under late stage development in an unrelated disease indication, thus the typical drug development risks are substantially reduced. The project will be a joint effort between a commercial entity whose staff has extensive experience in vascular photodynamic therapy and a research partner who is a leader in AV access preclinical and clinical research. This Phase I project will focus on validating this therapy in an established preclinical model of AV fistula maturation failure. If this project is successful, it is envisioned that this technology should be suitable for initial clinical feasibility studies within the near term.

项目摘要 - 光动力疗法预防动静脉瘘成熟失败：未满足的临床需求建立和维护动静脉 (AV) 通路对于患者来说至关重要血液透析。最优选的 AV 通路是前臂瘘管，现在用于大多数血液透析患者。然而，动静脉瘘的一个常见问题是原发性成熟失败，即手术放置后，其瘘管无法进行透析如果没有额外的经皮或手术干预，有些永远无法实现。这失败可能导致长期使用中心静脉导管和结果导致发病率增加给医疗保健系统带来巨大的财务成本。这尤其令人沮丧，因为它很好确定成熟的瘘管为血液透析患者提供了最有效的手段 AV 访问。虽然成熟失败的确切机制尚不完全清楚，但人们普遍认为术后新生内膜增生和静脉重塑不足发挥关键作用，预防这些过程中的任何一个都可以大大改善动静脉瘘结果。该项目将研究特定形式的光动力疗法的潜力，以改善瘘管成熟率。相关心血管模型的初步研究表明该疗法可能会对瘘管成熟失败的主要失败机制产生重大影响。从商业化的角度来看，这种疗法还具有已经处于研究阶段的优势。不相关疾病适应症的后期开发，因此典型的药物开发风险均大幅减少。该项目将由一家商业实体共同努力，该实体的工作人员在血管光动力治疗方面拥有丰富的经验，并且有一位研究伙伴 AV 接入临床前和临床研究的领导者。该一期项目将重点在已建立的 AV 临床前模型中验证该疗法瘘管成熟失败。如果这个项目成功，预计这项技术应该适合在短期内进行初步临床可行性研究。