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

超过40%的美国人患有肥胖症，肥胖率还在继续上升。负性肥胖 影响一般健康，并被归因于糖尿病、心脏病、血管疾病发病率的增加 疾病、关节应激、腰椎疾病、肝脏和胆道疾病，以及各种癌症。在之前的批准中 期间，我们开发了一种名为减肥动脉的微创、图像引导、经皮介入治疗。 栓塞症(BAE)，它在生长猪身上进行了测试，并转化为患者的I期临床试验，并 根据栓子大小和靶点位置以及安全原因，显示可减少生长猪的体重增加 人的体重减轻。虽然外科手术方法显示出比BAE更好的减肥效果，但它们 高度侵入性(需要重建肠道)，成功率不同，可以有显著的 并发症。因此，在这次续签申请中，我们寻求提炼和开发替代战略，以最低限度地 侵入性BAE和减肥。 使用新型微流控装置制造高通量的不透射线栓塞剂和抗反流 我们在生长猪身上进行了BAE，并证明了BAE对胃激素的影响，即， Ghrelin、胃泌素、GLP-1等，较小的栓子在减少体重增加方面更有效。然而， 较小的栓子也与包括胃部在内的严重不良事件的风险增加有关 穿孔。Ghrelin是主要的饥饿激素，主要在胃底产生，仍然是一种 减肥的主要目标。由于BAE将在其他健康的患者身上进行，因此非 靶向栓塞术(NTE)针对与胃共享相同血管供应的器官，如肝脏、 脾、胰腺也是一个令人担忧的问题。因此，关键问题，如改进的目标、安全性和长期- 需要进一步解决长期疗效问题，以便将这一过程从动物转化为患者 肥胖症的持久治疗。 在这项建议中，我们寻求使用放射性标记栓塞剂和第二次试验来提高BAE的安全性。 微创、图像引导减肥的新概念。我们将在肥胖的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 Y-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(MIONPs)联合磁热疗法(MHT)减肥；3)研制MR引导 迷走神经冷冻消融作为一种减肥策略来确定长期微创治疗技术 肥胖。

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.