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: 9061405
• 负责人: DARA L KRAITCHMAN
• 金额: $ 34.43万
• 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 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9061405
• 关键词: Address; Adverse effects; Affect; American; Anatomy; Animal Model; Animals; Appetite Stimulants; Architecture; Arterial Embolization; Arteries; Bariatrics; Biliary; Blood Vessels; Body Weight decreased; Body fat; Body mass index; Catheters; Cells; Clinic; Clinical; Data; Desire for food; Devices; Diabetes Mellitus; Diagnostic radiologic examination; Disease; Eating; Effectiveness; Endocrine; Endocrine Glands; Family suidae; Feeling; Food; Fundus; Gastric mucosa; Goals; Health; Healthcare; Heart Diseases; Hormones; Human; Hunger; Image; Imaging Techniques; Incidence; Injection of therapeutic agent; Injury; Intervention; Intestines; Left; Leptin; Life; Liver; Maintenance; Malignant Neoplasms; Maps; Methods; Modeling; Morbid Obesity; Nature; Obesity; Operative Surgical Procedures; Overweight; Pancreas; Patients; Penetration; Perioperative complication; Pharmaceutical Preparations; Phase I Clinical Trials; Prevalence; Procedures; Production; Reflux; Resolution; Risk; Risk Factors; Roentgen Rays; Role; Safety; Signal Transduction; Spinal Diseases; Spleen; Stomach; Structure; Techniques; Technology; Testing; Therapeutic Agents; Therapeutic Embolization; Time; Translating; Translations; Ulcer; United States; Vascular Diseases; Weight; Weight Gain; acute toxicity; cancer therapy; cone-beam computed tomography; cost; energy balance; gastric artery; gastric fundus; ghrelin; glucagon-like peptide; image guided; image guided intervention; image guided therapy; imaging system; improved; instrumentation; joint stress; minimally invasive; novel; obesity treatment; palliative; reconstruction; success; targeted delivery; tyrosyltyrosine

DESCRIPTION (provided by applicant): Approximately 127 million (65%) Americans are overweight, obese, or morbidly obese, and the number of obese Americans is rising. 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. Currently, there are no image-guided or percutaneous interventions or alternatives to the current invasive surgical techniques for the morbidly obese. Moreover, these surgical approaches have variable success rates, are highly invasive (requiring reconstruction of bowel), and can have significant complications. Thus, a critical need exists for minimally invasive bariatric procedures to reduce the perioperative complication rate and cost of bariatric therapy. A potent endogenous hunger stimulant, ghrelin, which is principally produced in the gastric fundus, has been a target for weight loss. No clinically viable, non-surgical approaches to modulate ghrelin production have been developed to-date. However, our group has manipulated ghrelin levels and altered weight gain via embolization of the arterial supply to the fundus of the stomach in pigs. Bariatric gastric Artery Embolization (BAE) is a complicated procedure as multiple vessels supply the stomach, and branches of these same vessels supply multiple other key structures, such as the spleen, pancreas, and liver. Thus, the risk of non-target embolization of these key structures as well as injury or ulceration to the gastric mucosa is a concern. Unlike embolic therapy for cancer which is primarily palliative, if successful BAE could allow patients to lose weight, lower risk factors for other diseases, and live long productiv lives. Thus, critical issues such as improved targeting, safety, and long term efficacy need to be further addressed in order to translate this procedure from the swine model into patients. In this proposal, we will improve BAE using advances in technology including specialized injection devices, X-ray visible embolic beads, and state-of-the-art X-ray imaging systems in order to produce a more complete fundal embolization with fewer adverse effects from non-target embolization and mucosal damage. Through this we hope to achieve prolonged ghrelin suppression and sustained weight loss. Our Specific Aims include: 1) Improved targeting of the gastric fundus using X-ray visible embolic beads of varying sizes, cone beam CT, and an anti-reflux embolic catheter; 2) Improved safety of BAE by assessing the effect of gastroprotective medications; and 3) determining the long term safety and efficacy of optimized BAE to both suppress ghrelin and alter weight.

描述（由申请人提供）：大约 1.27 亿 (65%) 美国人超重、肥胖或病态肥胖，并且肥胖美国人的数量正在增加。肥胖对整体健康产生负面影响，并导致糖尿病、心脏病、血管疾病、关节压力、腰椎疾病、肝脏和胆道疾病以及各种癌症的发病率增加。目前，对于病态肥胖者，还没有图像引导或经皮干预措施或当前侵入性手术技术的替代方法。此外，这些手术方法的成功率各不相同，具有高度侵入性（需要肠道重建），并且可能会产生严重的并发症。因此，迫切需要微创减肥手术来降低围手术期并发症发生率和减肥治疗成本。 生长素释放肽是一种有效的内源性饥饿刺激剂，主要在胃底产生，一直是减肥的目标。迄今为止，尚未开发出临床上可行的非手术方法来调节生长素释放肽的产生。然而，我们的研究小组通过栓塞猪胃底的动脉供应来控制生长素释放肽水平并改变体重增加。减肥胃动脉栓塞 (BAE) 是一个复杂的手术，因为有多个血管向胃供血，并且这些血管的分支向多个其他关键结构供血，例如脾脏、胰腺和肝脏。因此，这些关键结构的非目标栓塞以及胃粘膜损伤或溃疡的风险值得关注。与主要起到姑息作用的癌症栓塞疗法不同，如果成功的 BAE 可以让患者减轻体重，降低其他疾病的危险因素，并延长寿命。因此，需要进一步解决诸如改进靶向性、安全性和长期疗效等关键问题，以便将该程序从猪模型转化为患者。 在这个 根据提案，我们将利用先进的技术来改进 BAE，包括专用注射设备、X 射线可见栓塞珠和最先进的 X 射线成像系统，以产生更完整的宫底栓塞，减少非非药物的不良影响。 -目标栓塞和粘膜损伤。通过这一点，我们希望实现长期的胃饥饿素抑制和持续的体重减轻。我们的具体目标包括： 1) 使用不同尺寸的 X 射线可见栓塞珠、锥形束 CT 和抗反流栓塞导管，改善胃底的靶向性； 2) 通过评估胃保护药物的效果，提高 BAE 的安全性； 3) 确定优化的 BAE 抑制生长素释放肽和改变体重的长期安全性和有效性。