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上升。肥胖对总体健康产生负面影响，并已被归因于糖尿病、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，没有图像引导或经皮介入或替代当前侵入性手术技术。此外，这些手术方法具有可变的成功率，高度侵入性（需要肠重建），并且可能具有显著的并发症。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的成本。 胃饥饿素是一种有效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，我们的研究小组已经通过栓塞猪胃底的动脉供应来操纵胃饥饿素水平和改变体重增加。肥胖症胃动脉栓塞术（BAE）是一种复杂的手术，因为多根血管供应胃，这些相同血管的分支供应多个其他关键结构，如脾脏、胰腺和肝脏。因此，这些关键结构的非靶向栓塞以及胃粘膜损伤或溃疡的风险是一个问题。与主要是姑息性的癌症栓塞治疗不同，如果成功的BAE可以让患者减轻体重，降低其他疾病的风险因素，并延长生产寿命。因此，需要进一步解决关键问题，如改进的靶向、安全性和长期有效性，以便将该方法从猪模型转化为患者。 在这 根据该提案，我们将使用先进的技术改进BAE，包括专门的注射装置、X射线可见栓塞珠和最先进的X射线成像系统，以产生更完整的眼底栓塞，减少非靶栓塞和粘膜损伤的不良反应。通过这种方法，我们希望实现长期的ghrelin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靶向; 2）通过评估胃保护药物的作用改善BAE的安全性; 3）确定优化BAE抑制生长激素释放肽和改变体重的长期安全性和有效性。