A randomized control trial of G-POEM for gastroparesis to assess feasibility, safety, efficacy and physiological mechanisms

G-POEM 治疗胃轻瘫的随机对照试验，旨在评估可行性、安全性、有效性和生理机制

• 批准号: 10416023
• 负责人: MICHAEL L. CAMILLERI
• 金额: $ 59.4万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-15 至 2022-10-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10416023
• 关键词: Abdominal Pain; Adverse effects; Advocate; Age; Agonist; Antral; Area; Attention; Body mass index; Botulinum Toxins; Caliber; Chronic; Cicatrix; Clinic; Clinical; Clinical Research; Data; Demographic Factors; Denervation; Devices; Diabetes Mellitus; Diagnosis; Diet therapy; Disease; Dopamine; Electric Stimulation; Enteral; Etiology; Factor Analysis; Fibrinogen; Functional disorder; Future; Gastric Emptying; Gastrointestinal Motility; Gastroparesis; Giant Cells; Interstitial Cell of Cajal; Malnutrition; Measures; Mechanics; Metoclopramide; Motor; Nausea and Vomiting; Neurologic; Neuropathy; Nutritional Support; Obstruction; Operative Surgical Procedures; Opioid Analgesics; Oral; Outcome; Pathogenesis; Pathology; Patient Selection; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Physiological; Physiology; Placebos; Procedures; Psychological Factors; Pyloric sphincter structure; Pylorus; Questionnaires; Randomized; Randomized Controlled Trials; Refractory; Registries; Reporting; Resistance; Running; Safety; Severities; Solid; Stents; Stomach; Symptoms; Syndrome; Testing; Uncertainty; Uncontrolled Study; Universities; antagonist; base; cell motility; cost; demographics; diabetic; early satiety; effective therapy; efficacious treatment; excitatory neuron; experience; gastric retention; gastrointestinal symptom; improved; in vivo; inhibitory neuron; macrophage; motility disorder; novel; outcome prediction; panacea; predict responsiveness; premature; pressure; prospective; reduce symptoms; sham surgery; symptomatic improvement; tool; treatment effect; treatment optimization

ABSTRACT Gastroparesis is defined as a gastrointestinal motility disorder with objectively delayed gastric emptying of solids in the absence of mechanical obstruction, associated with upper gastrointestinal symptoms including early satiety, postprandial fullness, nausea, vomiting, bloating, and upper abdominal pain. The pathophysiology of gastroparesis includes postprandial antral hypomotility and pylorospasm, which may reflect extrinsic (vagal) denervation, enteric (intrinsic) neuropathy involving excitatory or inhibitory neurons or electrical syncytium (such as interstitial cells of Cajal) which may result from imbalance of CD206-positive macrophages that protect these intrinsic mechanisms. The introduction of G-POEM involving endoscopic pyloromyotomy has focused attention on pyloric dysfunction as a potentially important factor in the pathogenesis of this syndrome. However, many unknowns remain. First, the reported trials are uncontrolled with results that are short-term and inconsistent so the true efficacy of this procedure is not clear. Second, given that it is unlikely that G-POEM is a panacea for all patients, it is important to determine which of several possible factors influence outcome e.g. etiology (specifically diabetic versus idiopathic gastroparesis); demographic factors (age, BMI, psychological factors, duration of illness), baseline severity of gastric retention; gastric dysrhythmia, pyloric distensibility or scarring (as measured by EndoFLIP), postprandial antral motility and “isolated” pylorospasm (tonic elevation of baseline pressure independent of antral contractions). Our general hypothesis is that G-POEM is efficacious in relieving some or all symptoms of gastroparesis and that efficacy differs according to diagnosis, baseline retardation of gastric emptying, antropyloroduodenal motility and pyloric sphincter diameter and compliance. We will examine this hypothesis in a controlled short- term study that will inform future, more definitive trials on G-POEM on the optimal patient selection and outcome criteria. The aims of this pilot and feasibility, hypothesis-generating study are: Aim 1: To evaluate the 12-month treatment effect of peroral endoscopic pyloromyotomy (G-POEM) vs. sham surgery in patients with drug-refractory gastroparesis, as measured by validated questionnaires and to perform a pilot analysis of factors predictive of the outcome including demographics, etiology, vagal dysfunction, in vivo gastric physiology, (emptying of solids, postprandial antral motility, gastric dysrhythmia and pyloric motor functions). Aim 2. To compare the long-term (1 year or more) outcomes in patients randomized to G-POEM with matched patients prospectively followed in the national Gastroparesis registry run by the Gastroparesis Clinical Research Consortium (GpCRC). .

抽象的 胃轻瘫被定义为胃肠动力障碍，客观上胃排空延迟 在没有机械性梗阻的情况下摄入固体，与上消化道症状相关，包括 早饱、餐后饱胀、恶心、呕吐、腹胀、上腹痛。这 胃轻瘫的病理生理学包括餐后胃窦运动低下和幽门痉挛，这可能反映 外源性（迷走神经）去神经支配、涉及兴奋性或抑制性神经元的肠（内源性）神经病变或 电合胞体（例如卡哈尔间质细胞）可能是由于 CD206 阳性不平衡造成的 巨噬细胞保护这些内在机制。引入内窥镜G-POEM 幽门肌切开术将注意力集中在幽门功能障碍上，认为这是导致幽门螺杆菌感染的一个潜在重要因素。 该综合征的发病机制。然而，仍然存在许多未知数。首先，报告的试验是非对照的 结果是短期且不一致的，因此该程序的真正功效尚不清楚。第二， 鉴于 G-POEM 不太可能是适用于所有患者的灵丹妙药，因此确定以下几种方法中的哪一种非常重要 可能的因素影响结果，例如病因（特别是糖尿病与特发性胃轻瘫）； 人口因素（年龄、BMI、心理因素、病程）、胃潴留的基线严重程度； 胃节律失常、幽门扩张或疤痕（通过 EndoFLIP 测量）、餐后胃窦运动 和“孤立性”幽门痉挛（基线压力的强直性升高，与胃窦收缩无关）。 我们的一般假设是 G-POEM 可有效缓解胃轻瘫的部分或全部症状， 疗效因诊断、胃排空基线延迟、前十二指肠病变而异 蠕动性和幽门括约肌直径和顺应性。我们将在受控的短期内检验这个假设 学期研究将为未来更明确的 G-POEM 试验提供信息，以了解最佳患者选择和 结果标准。这项试点和可行性、假设生成研究的目的是： 目标 1：评估经口内镜下幽门肌切开术 (G-POEM) 与假手术的 12 个月治疗效果 通过经过验证的问卷测量，对药物难治性胃轻瘫患者进行手术，并进行 对预测结果的因素进行初步分析，包括人口统计学、病因学、迷走神经功能障碍、体内 胃生理学（固体排空、餐后胃窦运动、胃节律失常和幽门运动 功能）。 目标 2. 比较随机接受 G-POEM 的患者与匹配的患者的长期（1 年或更长）结果 由胃轻瘫临床中心管理的国家胃轻瘫登记处前瞻性随访的患者 研究联盟（GpCRC）。 。