Intestinal Lengthening via Distraction Enterogenesis for the Treatment of Short Bowel Syndrome

通过牵引肠发生延长肠以治疗短肠综合征

• 批准号: 10255884
• 负责人: Andre Bessette
• 金额: $ 42.32万
• 依托单位: ECLIPSE ENTEROGENESIS, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-12 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10255884
• 关键词: Adult; Age; Animal Model; Area; Caring; Cells; Child; Childhood; Chronic; Clinical Trials; Clip; Coiled Springs; Coin; Crohn' s disease; Data; Device Designs; Devices; Disease; Distal; Emerging Technologies; Enrollment; Ensure; Enteral; Excision; Family suidae; Feedback; Goals; Growth; Histologic; Human; Infection; Intestinal Atresia; Intestinal Obstruction; Intestinal Volvulus; Intestines; Ischemic Bowel Disease; Lead; Length; Life; Literature; Liver Failure; Location; Malabsorption Syndromes; Malignant Neoplasms; Measurement; Mechanics; Metals; Midgut; Monitor; Mus; Necrotizing Enterocolitis; Nutrient; Obstruction; Operative Surgical Procedures; Parenteral Nutrition; Patients; Perforation; Pharmaceutical Preparations; Phase; Population; Process; Publishing; Rattus; Reporting; Rodent Model; Safety; Sepsis; Short Bowel Syndrome; Small Intestines; Stomas; Stream; Surface; System; Techniques; Testing; Time; Tissues; Trauma; Weaning; animal data; base; cost; curative treatments; design; distraction; first-in-human; human study; in vivo; intestine surgery; mechanical device; meetings; mortality; new growth; nitinol; novel; nutrient absorption; operation; patient population; pediatric patients; porcine model; pre-clinical research; preclinical safety; preclinical study; regenerative tissue; restorative treatment; side effect

PROJECT SUMMARY Short Bowel Syndrome (SBS) is a rare, chronic, and devastating malabsorption condition where patients are unable to absorb enough nutrients naturally to sustain life. This condition is due to the loss of the majority of their small intestine from a massive surgical resection necessitated by certain diseases that destroy the small intestine. In the pediatric patient population, the most common diseases that lead to SBS are necrotizing enterocolitis, midgut volvulus, and intestinal atresia. In the adult population, diseases include Crohn’s, cancer, intestinal ischemia, and trauma. These conditions all result in the need for a massive resection of the small intestine leaving the patient without enough functional small intestine to absorb nutrients naturally. Current chronic therapies for SBS include, parenteral nutrition, expensive daily medication and intestinal surgery, which come at a staggering average 5-year cost of $1.6M per patient. It is estimated that the first year of treatment for a pediatric SBS patient is in excess of $500,000. Complications from daily parenteral nutrition include liver failure and central line infections (sepsis). Mortality rates as high as 30% by age 5 have been reported and none of the currently available treatments for SBS restore natural absorption of nutrients. Over the last decade, intestinal lengthening via distraction enterogenesis has emerged as a potential restorative treatment option for patients with short bowel syndrome. Preclinical research has shown that mechanical distraction devices can stimulate the growth of healthy small intestine tissue in multiple animal models. Literature has shown that for every additional 1% of expected small bowel a child possesses, the odds of weaning from parenteral support increases by 3% (Belza et al, 2019). The goal of this project is to move this emerging technology from the lab to the bedside by completing an FDA requested pre-clinical study, receiving IDE approval, and conducting a First-In-Human clinical trial. The Phase I portion of the project will produce the pre-clinical safety data on the final design of the Eclipse XL1 distraction enterogenesis device required for FDA IDE submission. Based on feedback from the FDA, Phase II will produce the First In Human clinical trial data in a stepwise fashion to ensure safety and probable benefit. If successful, this novel treatment will revolutionize the care of SBS patients and potentially return them to enteral autonomy.

项目摘要 短肠综合征（SBS）是一种罕见的，慢性的和破坏性的吸收不良的条件， 病人无法自然吸收足够的营养来维持生命。这种情况是由于 他们的大部分小肠因大规模手术切除而丢失， 某些破坏小肠的疾病。 在儿科患者人群中，导致SBS的最常见疾病是坏死性疾病 小肠结肠炎、中肠扭转和肠闭锁。在成年人中，疾病包括 克罗恩病、癌症、肠道缺血和创伤。这些条件都导致需要 小肠的大面积切除使患者没有足够的功能性小肠， 肠道自然吸收营养。 目前SBS的慢性疗法包括肠外营养、昂贵的每日药物治疗和 肠道手术，这是一个惊人的平均5年成本为160万美元的病人。是 据估计，儿童SBS患者第一年的治疗费用超过50万美元。 每日肠外营养的并发症包括肝功能衰竭和中心静脉感染 （败血症）。据报道，5岁以下儿童的死亡率高达30%，目前没有一个儿童死亡。 SBS的可用治疗恢复营养素的自然吸收。 在过去的十年里，通过牵张肠形成的肠延长已经成为一种新的治疗方法。 短肠综合征患者的潜在恢复性治疗选择。临床前 研究表明，机械牵引装置可以刺激健康的生长， 在多种动物模型中的小肠组织。文献表明，每增加一个 1%的预期小肠的孩子拥有，从肠外支持断奶的几率 增加3%（Belza et al，2019）。这个项目的目标是将这个新兴的 通过完成FDA要求的临床前研究， 获得IDE批准，并进行首次人体临床试验。 该项目的I期部分将产生最终设计的临床前安全性数据， FDA IDE提交所需的Eclipse XL1牵张肠生成装置。基于 根据FDA的反馈，第二阶段将逐步产生首次人体临床试验数据。 时尚，以确保安全和可能的利益。如果成功，这种新的治疗方法将 彻底改变SBS患者的护理，并可能使他们恢复肠内自主性。