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

项目摘要/摘要 该项目的最终目标是开发灵活的、非闭塞的Ω-Cuff作为一种简单而安全的装置 治疗胃食管反流病(GERD)。GERD是指下食道括约肌(LES)无力 为了防止酸性胃内容物过度回流到食道，这可能会导致严重的 不适，扰乱日常生活，可导致食管炎、巴雷特食道、狭窄和癌症。 4000万美国Gerd患者通过Proton等终身处方药控制症状 泵抑制剂(PPI)，其中1600万人将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，每年在美国的医疗费用为120亿美元。 不断增长。由于其风险和显著的生理干扰，黄金标准的眼底折叠术 治疗3万名患者。Ω-Cuff在不太严重的部分胃底折叠术的基础上进行了改进 更简单、更容易、更安全、更持久的治疗。一种简单的腹腔镜手术放置Ω袖口 在不改变解剖或生理的情况下直接进入食道。Ω-Cuff与 食道，以减轻吞咽困难常见的其他外科治疗，以减少药物依赖和 医疗保健成本。 我们成功地完成了所需的临床前安全性测试。制作并植入Ω袖带。 在LES地区进行了一项为期1年的24头猪的良好实验室操作规范(GLP)研究，没有不良事件。这个 该装置可以安全地移植。Ω-Cuff通过了ISO 10993生物相容性、耐腐蚀性、镍 淋洗和疲劳循环耐久性测试。它还被发现在1.5和3.0版本中都与MRI兼容 特斯拉水平，允许患者在需要时安全地进行标准MRI诊断。一份调查报告 设备豁免(IDE)已被食品和药物管理局(FDA)批准用于临床可行性 学习。这项建议有以下目标。具体目标1：为临床制作5种尺寸的Ω袖口 学习。根据FDA的要求，我们将为临床研究生产5种尺寸(每种20种)。具体目标2：行为 人类临床早期可行性研究8例。这项研究是观察性的、前瞻性的、非 对接受Ω-Cuff装置的患者进行随机、开放标签的可行性研究，以评估Ω-Cuff装置的安全性 袖套及其在增强LES功能中减轻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。这项临床试验的目的是 可行性研究是为扩展为完成临床验证的关键研究奠定基础 进程。在完成关键的临床研究并获得批准后，将开始商业化 从美国食品和药物管理局到第三阶段上市Ω-Cuff。

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.