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: 10705620
• 负责人: Andre Bessette
• 金额: $ 81.36万
• 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: 2021-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10705620
• 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; 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; Probability; Process; Publishing; Rattus; Reporting; Rodent Model; Safety; Sepsis; Short Bowel Syndrome; Small Intestines; Stomas; Stream; Surface; System; Techniques; Testing; Time; Tissues; Trauma; Weaning; absorption; animal data; cost; curative treatments; design; distraction; first-in-human; human study; in vivo; intestine surgery; manufacture; 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; transmission process

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.

项目概要 短肠综合症 (SBS) 是一种罕见的、慢性的、破坏性的吸收不良疾病， 患者无法自然吸收足够的营养来维持生命。这种情况是由于 由于大规模手术切除而失去了大部分小肠 某些破坏小肠的疾病。 在儿科患者群体中，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。在成年人口中，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 小肠的大量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、昂贵的日常药物和 肠道手术，每名患者 5 年的平均费用高达 160 万美元，令人震惊。这是 据估计，儿童 SBS 患者第一年的治疗费用超过 500,000 美元。 每日肠外营养的并发症包括肝衰竭和中心静脉导管感染 （败血症）。据报道，5 岁死亡率高达 30%，目前还没有 SBS 的可用治疗方法可恢复营养物质的自然吸收。 在过去的十年中，通过牵引肠发生来延长肠道已成为一种 短肠综合征患者潜在的恢复性治疗选择。临床前 研究表明，机械牵引装置可以刺激健康的成长 多种动物模型中的小肠组织。文献表明，每增加一个 儿童拥有预期小肠的 1%，即脱离肠外支持的几率 增加了 3%（Belza 等人，2019）。该项目的目标是推动这一新兴的 通过完成 FDA 要求的临床前研究，从实验室到临床的技术， 获得 IDE 批准，并进行首次人体临床试验。 该项目的第一阶段部分将产生最终设计的临床前安全数据 FDA IDE 提交所需的 Eclipse XL1 牵引肠发生装置。基于 根据FDA反馈，二期将逐步产生首次人体临床试验数据 确保安全和可能利益的时尚。如果成功的话，这种新颖的治疗方法将 彻底改变 SBS 患者的护理，并有可能使他们恢复肠内自主权。

项目成果

Long-term safety of intraluminal spring-mediated bowel lengthening.

腔内弹簧介导的肠延长的长期安全性。

• DOI: 10.1016/j.jpedsurg.2022.09.034
• 发表时间: 2023
• 期刊: Journal of pediatric surgery
• 影响因子: 2.4
• 作者: Rafeeqi,Talha;Sullins,VeronicaF;Thomas,Anne-Laure;Wagner,JustinP;Wood,LaurenSY;Salimi-Jazi,Fereshteh;Bessette,Andre;Dunn,JamesCY
• 通讯作者: Dunn,JamesCY