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: 10211000
• 负责人: MICHAEL L. CAMILLERI
• 金额: $ 60.64万
• 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 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10211000
• 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; base; cell motility; control trial; 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). .

摘要 胃轻瘫是指胃动力障碍，客观上胃排空延迟， 在没有机械性梗阻的情况下，与上消化道症状相关的固体，包括 早饱、餐后饱胀、恶心、呕吐、腹胀和上腹部疼痛。的 胃轻瘫的病理生理学包括餐后胃窦低动力和幽门痉挛，这可能反映了 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，或 电合胞体（如Cajal间质细胞），这可能是由于CD 206阳性细胞的不平衡造成的。 巨噬细胞保护这些内在机制。内镜下G-POEM的介绍 幽门环肌切开术已将注意力集中在幽门功能障碍上，认为这是幽门狭窄的潜在重要因素。 此综合征的发病机制。然而，仍有许多未知数。首先，报告的试验是不受控制的 其结果是短期的和不一致的，因此该程序的真正功效尚不清楚。第二、 考虑到G-POEM不可能是所有患者的灵丹妙药，确定几种方法中的哪一种是重要的， 影响结局的可能因素，例如病因（特别是糖尿病与特发性胃轻瘫）; 人口统计学因素（年龄、BMI、心理因素、病程）、基线胃潴留严重程度; 胃节律障碍、幽门扩张性或瘢痕形成（通过EndoFLIP测量）、餐后胃窦运动 和“孤立性”幽门痉挛（不依赖于胃窦收缩的基线压力的强直性升高）。 我们的一般假设是，G-POEM在缓解胃轻瘫的部分或全部症状方面是有效的， 根据诊断、基线胃排空延迟、胃窦十二指肠 幽门括约肌直径和顺应性。我们将在一个受控的短- 长期研究，将为未来更明确的G-POEM试验提供最佳患者选择信息， 结果标准。这项试验性和可行性假设生成研究的目的是： 目的1：评价经口内镜幽门环肌切开术（G-POEM）与假手术的12个月治疗效果 药物难治性胃轻瘫患者的手术，通过有效的问卷调查进行测量， 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、胃节律障碍和幽门运动 职能）。 目标2.比较随机分配至G-POEM组的患者的长期（1年或以上）结局， 在由胃轻瘫临床研究中心运行的国家胃轻瘫登记处前瞻性随访的患者 研究联盟（GpCRC）。 .