Image-guided Bariatric Arterial Embolization (BAE) for the Treatment of Obesity

图像引导肥胖动脉栓塞术 (BAE) 治疗肥胖症

• 批准号: 10593586
• 负责人: DARA L KRAITCHMAN
• 金额: $ 69.1万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-01 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10593586
• 关键词: 90Y; Address; Affect; American; Animal Model; Animals; Arterial Embolization; Attenuated; Bariatrics; Biliary; Blood Vessels; Body Weight decreased; Body mass index; Brain; Canis familiaris; Catheters; Cells; Client; Clinical; Clinical Trials; Complex; Cryosurgery; Data; Desire for food; Diabetes Mellitus; Diameter; Disease; Embolism; Encapsulated; Endocrine; Equipment; Esophagogastric Junction; Family suidae; Feeling; Funding; Fundus; Gastric ulcer; Gastrins; Gastritis; Goals; Grant; Health; Heart Diseases; Hormonal; Hormones; Human; Hunger; Hyperthermia; Image; Imaging Device; Imaging Techniques; Incidence; Injury; Intervention; Intestines; Ischemia; Label; Liver; Location; Magnetism; Malignant Neoplasms; Medical Care Costs; Microfluidic Microchips; Microfluidics; Microspheres; Modeling; Morbid Obesity; Obesity; Operative Surgical Procedures; Organ; Overweight; Pancreas; Patients; Perforation; Persons; Phase I Clinical Trials; Prevalence; Procedures; Production; Progress Reports; Radioactive; Radioembolization; Radiolabeled; Reflux; Risk; Safety; Satiation; Serious Adverse Event; Signal Transduction; Spinal Diseases; Spleen; Stomach; Structure; Techniques; Testing; Therapeutic Embolization; Translating; Translations; Ulcer; United States; Vagus nerve structure; Vascular Diseases; Vascular blood supply; Weight; Weight Gain; appetite loss; bariatric surgery; cancer therapy; canine model; clinically relevant; cone-beam computed tomography; cost; gastric artery; gastric fundus; ghrelin; glucagon-like peptide 1; heat injury; hyperthermia treatment; image guided; image guided therapy; improved; increased appetite; iron oxide nanoparticle; joint stress; meter; minimally invasive; negative affect; novel; novel strategies; obese patients; obesity treatment; reconstruction; soft tissue; success; targeted delivery; translation to humans; tumor

Over 40% of Americans are obese, with the prevalence of obesity continuing to rise. Obesity negatively affects general health and has been attributed to an increasing incidence of diabetes, heart disease, vascular disease, joint stress, lumbar spine disorders, liver and biliary disease, and various cancers. In the prior granting period, we developed a minimally invasive, image-guided, percutaneous intervention called bariatric arterial embolism (BAE), which was tested in growing swine and translated to a Phase I clinical trial in patients, and was shown to decrease weight gain in growing pigs based on embolic size and target location and safely cause weight loss in people. While surgical approaches have shown better reductions in weight than BAE, they are highly invasive (requiring reconstruction of bowel), have variable success rates, and can have significant complications. Thus, in this renewal application, we seek to refine and develop alternative strategies for minimally invasive BAE and weight reduction. Using a novel microfluidic device to create high-throughput radiopaque embolics and an anti-reflux catheter, we performed BAE in growing swine and demonstrated the effects of BAE on gastric hormones, i.e., ghrelin, gastrin, GLP-1, etc. with smaller embolics being more effective at reducing weight gain. However, smaller embolics are also associated with increased the risk of severe adverse events including gastric perforation. Ghrelin, the primary hunger hormone, which is produced primarily in the gastric fundus, remains a major target for weight reduction. As BAE would be performed in otherwise healthy patients, the risk of non- target embolization (NTE) to organs that share the same vascular supply as the stomach, such as the liver, spleen, pancreas, remains a concern as well. Thus, critical issues such as improved targeting, safety, and long- term efficacy need to be further addressed in order to translate this procedure from animals into patients as a durable treatment for obesity. In this proposal, we seek to improve the safety of BAE using radiolabeled embolics as well as test two new concepts for minimally invasive, image-guided weight loss. We will test these techniques in obese dogs rather than growing pigs as a more realistic model of obesity in people. Our Specific Aims include: 1) Evaluate the safety and efficacy of Yttrium-90 labeled embolics for BAE; 2) Evaluate microencapsulated, iron-oxide nanoparticle (MIONPs) combined with magnetic hyperthermia (MHT) for weight loss; and 3) Develop MR-guided vagal cryoablation as a weight-loss strategy to determine long-term minimally invasive techniques for treating obesity.

超过40%的美国人肥胖，肥胖的患病率继续上升。肥胖消极 影响一般健康，并已归因于糖尿病、心脏病、血管性疾病、 疾病、关节压力、腰椎疾病、肝脏和胆道疾病以及各种癌症。在先前授予 在此期间，我们开发了一种微创，图像引导，经皮介入治疗，称为肥胖动脉 栓塞（BAE），这是在生长的猪进行测试，并转化为患者的I期临床试验， 根据栓塞尺寸和靶位置，显示可降低生长猪的体重增加， 人的体重减轻。虽然手术方法显示出比BAE更好的减肥效果，但它们 高度侵入性（需要肠重建），有不同的成功率，并可能具有显著的 并发症因此，在此更新申请中，我们寻求优化和开发替代策略， 侵入性BAE和减肥 使用新型微流体装置来产生高通量不透射线栓塞剂和抗反流剂 导管，我们在生长猪中进行了BAE，并证明了BAE对胃激素的影响，即， 胃饥饿素、胃泌素、GLP-1等，其中较小的栓塞剂在减少体重增加方面更有效。然而，在这方面， 较小的栓塞也与严重不良事件的风险增加有关， 穿孔胃饥饿素是主要的饥饿激素，主要在胃底产生， 减肥的主要目标。由于BAE将在其他方面健康的患者中进行， 靶向栓塞（NTE）到与胃共享相同血管供应的器官，如肝脏， 脾脏胰腺也是个问题因此，关键问题，如改进的靶向，安全性和长期- 为了将该方法从动物转化为患者， 肥胖症的持久治疗。 在这个建议中，我们试图提高使用放射性标记栓塞剂的BAE的安全性，以及试验二 微创、影像引导减肥的新概念。我们将在肥胖狗身上测试这些技术 而不是把养猪作为人类肥胖的更现实的模型。我们的具体目标包括：1）评估 钇-90标记栓塞剂治疗BAE的安全性和有效性; 2）评价微囊化氧化铁 纳米粒子（MIONP）结合磁热疗（MHT）用于减肥;以及3）开发MR引导的 迷走神经冷冻消融术作为一种减肥策略，以确定长期微创技术治疗 肥胖