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

基本信息

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
项目类别：
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

项目摘要

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，且肥胖患病率持续上升。肥胖带来负面影响影响整体健康，导致糖尿病、心脏病、血管疾病的发病率增加疾病、关节压力、腰椎疾病、肝脏和胆道疾病以及各种癌症。在之前的授予中在此期间，我们开发了一种微创、图像引导、经皮介入治疗，称为肥胖动脉治疗栓塞（BAE），在生长猪中进行了测试，并转化为针对患者的 I 期临床试验，根据栓塞大小和目标位置，可以减少生长猪的体重增加，并安全地引起人们体重减轻。虽然手术方法比 BAE 更能减轻体重，但它们高度侵入性（需要肠道重建），成功率各不相同，并且可能有显着的影响并发症。因此，在这个更新应用程序中，我们寻求完善和开发最小化的替代策略侵入性 BAE 和减肥。使用新型微流体装置创建高通量不透射线栓塞和抗反流我们在生长猪中进行了 BAE，并证明了 BAE 对胃激素的影响，即生长素释放肽、胃泌素、GLP-1 等，栓塞较小，可更有效地减少体重增加。然而，较小的栓塞还与严重不良事件（包括胃病）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，仍然是一种主要目标是减重。由于 BAE 将在其他方面健康的患者中进行，因此存在非对与胃具有相同血管供应的器官进行靶向栓塞（NTE），例如肝脏，脾脏、胰腺也仍然是一个问题。因此，诸如改进目标、安全性和长期使用等关键问题需要进一步解决长期疗效问题，以便将这一过程从动物身上转化为患者身上肥胖症的持久治疗。在本提案中，我们寻求使用放射性标记栓塞来提高 BAE 的安全性，并测试两个微创、图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将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 标记栓塞用于 BAE 的安全性和有效性； 2) 评估微胶囊化的氧化铁纳米粒子（MIONP）与磁热疗（MHT）相结合用于减肥； 3）开发MR引导迷走神经冷冻消融作为一种减肥策略，以确定长期微创治疗技术肥胖。