Clinical Feasibility Study of a Novel Flexible, Non-occlusive GERD Treatment Device

新型灵活、非闭塞性胃食管反流病治疗装置的临床可行性研究

• 批准号: 10256212
• 负责人: Claude NMN Tihon
• 金额: $ 59.65万
• 依托单位: CT RESOURCES, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10256212
• 关键词: Adopted; Adverse event; Affect; Amendment; American; Anatomy; Area; Back; Barrett Esophagus; Chronic Disease; Clinical; Clinical Protocols; Clinical Research; Clinical Trials; Corrosion; Data; Deglutition; Deglutition Disorders; Dependence; Device Safety; Devices; Diagnosis; Disease; Disease Progression; Drug Prescriptions; Drug usage; Enrollment; Esophageal Adenocarcinoma; Esophageal Stenosis; Esophagitis; Esophagus; Family suidae; Fatigue; Feasibility Studies; Fibrosis; Food; Fundoplication; Gastroenterologist; Gastroesophageal reflux disease; Goals; Gold; Grant; Health Care Costs; Hour; Human; Implant; Inferior esophageal sphincter structure; Investigation; Lead; Life; Magnetic Resonance Imaging; Malignant Neoplasms; Marketing; Nickel; Open Bite; Operative Surgical Procedures; Outcome; Patients; Performance; Pharmaceutical Preparations; Phase; Physiological; Physiology; Preparation; Procedures; Process; Proton Pump Inhibitors; Quality Control; Quality of life; Recommendation; Reflux; Refractory; Report (document); Reporting; Research Personnel; Resistance; Resources; Risk; Safety; Shoes; Side; Site; Small Business Innovation Research Grant; Stomach; Stomach Content; Surface; Surgeon; Surgical sutures; Symptoms; Techniques; Testing; Time; Time Study; United States; United States Food and Drug Administration; Validation; Work; arm; biomaterial compatibility; commercial application; commercialization; design; experience; feasibility trial; first-in-human; flexibility; good laboratory practice; health related quality of life; implantable device; improved; innovation; meetings; metallicity; nitinol; novel; open label; pandemic disease; patient safety; preclinical safety; pressure; prospective; reduce symptoms; safety testing; sample fixation; side effect; skills

PROJECT SUMMARY/ABSTRACT The ultimate goal of this project is to develop the flexible, non-occlusive Ω-Cuff as a simple and safe device to treat gastroesophageal reflux disease (GERD). GERD is the inability of the lower esophageal sphincter (LES) to keep the acidic stomach content from coming back up excessively into the esophagus that can cause major discomfort, disrupting daily lives and can lead to esophagitis, Barrett's esophagus, strictures, and cancer. 40 million U.S. GERD patients manage their symptoms by life-long prescription medications such as Proton Pump Inhibitors (PPIs) of whom 16 million will need other options due to either ineffectiveness or side effects. GERD is the most expensive of all the GI diseases, with an annual U.S. healthcare cost >$12 billion and growing. Due to its risks and significant physiological perturbations, the gold standard fundoplication surgery treats <30 thousand patients. Ω-Cuff improves upon a less morbid partial fundoplication surgery by having a simpler, easier, safer and more durable treatment. A straightforward laparoscopic procedure places the Ω-Cuff directly onto the esophagus without altering anatomy or physiology. Ω-Cuff works symbiotically with the esophagus to mitigate dysphagia common to other surgical treatments, to reduce medication dependence and healthcare costs. We successfully completed the required preclinical safety tests. Ω-Cuffs were manufactured and implanted over the LES area in a 1-year, 24-pigs Good Laboratory Practice (GLP) study without adverse events. The device could be safely explanted. Ω-Cuff passed the panel of ISO 10993 biocompatibility, corrosion, nickel leaching, and fatigue cycling durability tests. It was also found to be MRI compatible at both the 1.5 and 3.0 Tesla levels, allowing patients to safely go through standard MRI diagnoses, if needed. An Investigational Device Exemption (IDE) has been granted by the Food and Drug Administration (FDA) for a clinical feasibility study. This proposal has the following aims. Specific Aim 1: Manufacture Ω-Cuff in 5 sizes for the clinical study. Per FDA mandate, we will manufacture 5 sizes (20 each) for the clinical study. Specific Aim 2: Conduct human clinical early feasibility study with 8 patients. The study is an observational, prospective, non- randomized, open label, feasibility study of patients receiving the Ω-Cuff device, to evaluate the safety of Ω- Cuff and its ability to reduce the GERD symptoms in augmenting the function of the LES. Specific Aim 3: Prepare report and document for an IDE amendment to expand into a pivotal study. The intent of this clinical feasibility study is to establish a basis for expanding into a pivotal study to complete the clinical validation process. Commercialization will commence after completion of the pivotal clinical study and receiving approval from the FDA to market Ω-Cuff in Phase III.

项目总结/摘要 本项目的最终目标是开发一种简单安全的柔性非闭塞性袖带， 治疗胃食管反流病（GERD）。GERD是下食管括约肌（LES）无力 以防止酸性胃内容物过多地返回食道， 这可能会导致不适，扰乱日常生活，并可能导致食管炎，巴雷特食管，狭窄和癌症。 4000万美国GERD患者通过终身处方药（如Proton）来控制症状 泵抑制剂（PPI），其中1600万人由于无效或副作用而需要其他选择。 GERD是所有胃肠道疾病中最昂贵的，美国每年的医疗费用超过120亿美元， 增长.由于其风险和重大的生理扰动，金标准胃底折叠手术 治疗<3万名患者。双袖带改善了病态较少的部分胃底折叠手术， 更简单、更容易、更安全和更持久的治疗。一个简单的腹腔镜手术将袖套 直接作用于食管而不改变解剖学或生理学。袖带-袖带与 食管，以减轻其他手术治疗常见的吞咽困难，减少药物依赖， 医疗费用。 我们成功完成了所需的临床前安全性测试。制造并植入指套 在为期1年、24头猪的药物非临床研究质量管理规范（GLP）研究中，在LES区域内无不良事件。的 设备可以安全地安装。指套通过了ISO 10993生物相容性、腐蚀性、镍的测试 浸出和疲劳循环耐久性测试。还发现它在1.5和3.0下都是MRI兼容的 特斯拉水平，允许患者安全地通过标准MRI诊断，如果需要的话。试验用 美国食品药品监督管理局（FDA）已批准器械豁免（IDE），以确定其临床可行性 study.这项建议的目的如下。具体目标1：制造5种尺寸的临床用肩袖 study.根据FDA要求，我们将为临床研究生产5种尺寸（每种20件）。具体目标2：行为 8例患者的人类临床早期可行性研究。该研究是一项观察性、前瞻性、非 对接受指套器械的患者进行随机、开放标签、可行性研究，以评价指套器械的安全性， 袖带及其在增强LES功能中减少GERD症状的能力。具体目标3： 为IDE修正案准备报告和文件，以扩展为关键研究。本次临床试验的目的 可行性研究是为扩展为关键性研究以完成临床验证奠定基础 过程将在关键临床研究完成并获得批准后开始商业化 从食品药品监督管理局到市场的第三阶段。