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: 8651916
• 负责人: DARA L KRAITCHMAN
• 金额: $ 33.39万
• 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 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8651916
• 关键词: Acute; Address; Adverse effects; Affect; American; Anatomy; Animal Model; Animals; 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; System; Techniques; Technology; Testing; Therapeutic Agents; Therapeutic Embolization; Time; Toxic effect; Translating; Translations; Ulcer; United States; Vascular Diseases; Weight; Weight Gain; cancer therapy; cone-beam computed tomography; cost; energy balance; gastric artery; gastric fundus; ghrelin; glucagon-like peptide; image guided intervention; image guided therapy; improved; instrumentation; joint stress; minimally invasive; novel; obesity treatment; palliative; public health relevance; 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，而且肥胖美国人的数量正在上升。肥胖会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不断上升。目前，没有图像引导或经皮干预或替代目前的侵入性手术技术治疗病态肥胖。此外，这些手术方法成功率不同，具有高度侵入性（需要重建肠道），并且可能有明显的并发症。因此，迫切需要微创减肥手术，以减少围手术期并发症的发生率和减肥治疗的成本。胃饥饿素是一种强有力的内源性饥饿刺激物，主要在胃底产生，一直是减肥的目标。迄今为止，还没有临床可行的非手术方法来调节胃饥饿素的产生。然而，我们的研究小组通过栓塞猪胃底动脉供应来控制胃促生长素水平并改变体重增加。胃动脉栓塞术（BAE）是一项复杂的手术，因为胃有多条血管供应，这些血管的分支供应其他多个关键结构，如脾脏、胰腺和肝脏。因此，这些关键结构的非靶栓塞以及胃黏膜损伤或溃疡的风险是一个值得关注的问题。与栓塞治疗癌症不同，栓塞治疗主要是姑息性的，如果成功，BAE可以让患者减肥，降低其他疾病的风险因素，并延长寿命。因此，需要进一步解决诸如改进靶向性、安全性和长期有效性等关键问题，以便将这种方法从猪模型转化为患者。在这个