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A Novel Endovascular Approach to Remove Atherosclerotic Plaque Lesions In Situ

一种原位去除动脉粥样硬化斑块病变的新型血管内方法

基本信息

批准号：
10084300
负责人：
Melina Rae Kibbe
金额：
$ 71.17万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-01-01 至 2021-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10084300
关键词：
Affect Aneurysm Angiography Animal Model Area Arterial Fatty Streak Arteries Atherosclerosis Balloon Angioplasty Balloon Occlusion Blood Blood Vessels Calcium Cardiovascular Diseases Carotid Arteries Catheters Cause of Death Cells Clinical Coagulation Process Collagen Complement Activation Custom Data Development Digestion Dilatation - action Dissection Distal Elastases Embolism Endothelium FDA approved Family suidae Fibrin Goals Health Human Hyperplasia Immunohistochemistry In Situ In Situ Lesion Individual Inflammation Inflammatory Intervention Knowledge Lead Life Lipids Longitudinal Studies Mechanics Metals Methods Mission Outcome Measure Phase I Clinical Trials Platelet aggregation Procedures Proteoglycan Research Personnel Safety Secondary to Smooth Muscle Myocytes Sonication Stents Superficial Femoral Artery Techniques Technology Testing Thick Thrombosis Time Trauma Tumor Debulking Ultrasonography United States United States National Institutes of Health Vasomotor base clinically relevant conventional therapy disability efficacy study first-in-human heat injury iliac artery improved outcome in vivo Model innovation medical specialties multidisciplinary new technology non-compliance novel optimal treatments porcine model pre-clinical restenosis safety study sex systemic inflammatory response targeted agent time use

项目摘要

SUMMARY Cardiovascular disease secondary to atherosclerosis is the leading cause of death in the United States. Current percutaneous vascular interventions that treat severe atherosclerosis require inflation of a balloon with or without deployment of a rigid, non-compliant metal stent. Yet, this technique fails to remove the atherosclerotic plaque burden and causes mechanical trauma to the arterial wall, resulting in significant restenosis rates. FDA-approved plaque debulking technologies do exist and are used in the clinical arena. However, to debulk the plaque, each of these therapies induces some form of mechanical or thermal injury to the vessel wall, which ultimately stimulates the development of neointimal hyperplasia and results in significant arterial restenosis. Therefore, the goal of this study is to develop a novel endovascular technology to reduce atherosclerotic plaque burden without inducing thermal or mechanical trauma to the arterial wall. Our paradigm-shifting technology is based on a safe method of digesting atherosclerotic plaque in situ through the use of a double occlusion balloon catheter, sonication wire, and a highly customized solution tailored to safely digest atherosclerotic plaque. Given that most atherosclerotic plaques are composed of collagen, fibrin, lipids, proteoglycans, inflammatory cells, smooth muscle cells, and calcium, we hypothesize that a digestion solution containing agents that target these plaque components will dissolve and digest the plaque in situ within a clinically relevant time frame. Avoidance of the use of elastases in our solution limits digestion of the plaque to the elastic lamina. With our multidisciplinary team of investigators, we have already demonstrated the feasibility and initial safety of our approach through preliminary data. We have demonstrated effective digestion of excised human carotid artery atherosclerotic plaques as well as the plaque inside intact human superficial femoral arteries. We have evaluated our approach in a non-atherosclerotic porcine model in vivo and showed that our therapy did not injure the arterial wall, was limited to the internal elastic lamina, and did not result in dissections or aneurysm formation, suggesting that our therapy is safe. Lastly, we evaluated our approach in an atherosclerotic porcine model and demonstrated initial efficacy at reducing plaque without inducing thrombosis or aneurysmal degeneration. Given the feasibility and promise of these preliminary data, we believe further scientific exploration and development of this novel technology is warranted and will lead to an innovative clinical therapy for the treatment of atherosclerosis in humans. Thus, the overall objective of this proposal is to robustly evaluate the safety, efficacy, durability, and repeatability of this therapy in a preclinical porcine animal model of atherosclerosis. Successful completion of these studies will directly lead to an FDA application for a first-in-human Phase 1 clinical trial, and is thus highly aligned with the mission of the National Institutes of Health to “enhance health, lengthen life, and reduce illness and disability” through the application of new knowledge.

总结