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 胃轻瘫被定义为胃肠动力障碍，其客观上表现为胃排空障碍。 无机械阻塞的固体物质，与上消化道症状有关，包括 早饱、餐后饱、恶心、呕吐、腹胀和上腹部疼痛。这个 胃轻瘫的病理生理包括餐后胃窦动力减退和幽门痉挛，这可能反映了 外源性(迷走神经)失神经、肠(内源性)神经病，涉及兴奋性或抑制性神经元或 CD206阳性表达失衡所致的电合体(如Cajal间质细胞) 保护这些内在机制的巨噬细胞。涉及内窥镜的G-PEND介绍 幽门肌切开术将注意力集中在幽门功能障碍上，认为这是 这种综合征的发病机制。然而，仍有许多未知数。首先，报道的试验不受控制 由于结果是短期的和不一致的，所以这一程序的真正效果尚不清楚。第二, 鉴于G-POSE不太可能是所有患者的灵丹妙药，确定以下哪种是重要的 可能影响预后的因素，例如病因(特别是糖尿病与特发性胃轻瘫)； 人口统计因素(年龄、体重指数、心理因素、病程)、胃滞留的基线严重程度； 胃电节律紊乱、幽门扩张或疤痕形成(根据EndoFLIP测量)、餐后胃窦动力 和“孤立性”幽门痉挛(不依赖胃窦收缩的紧张性基线压力升高)。 我们的一般假设是，G-PENG在缓解部分或全部胃瘫症状方面有效，并 疗效因诊断、基线胃排空障碍、十二指肠安慰剂而异。 幽门括约肌直径和顺应性。我们将在受控短文中检验这一假说- 术语研究，将为未来关于G-PENG的最佳患者选择和更明确的试验提供信息 结果标准。这项试验性和可行性研究的目的是： 目的1：比较经口腔内窥镜幽门肌切开术(G-POEM)与假手术12个月的疗效。 药物难治性胃轻瘫患者的手术治疗 对包括人口学、病因学、迷走神经功能障碍在内的预后因素进行体内预测的初步分析 胃生理(固体排空、餐后胃窦运动、胃电节律失常和幽门运动) 函数)。 目的2.比较随机接受G-POSE和配对的患者的长期(一年或更长)结果 在由胃瘫临床中心运营的全国胃瘫登记系统中，前瞻性地对患者进行跟踪调查 研究联盟(GpCRC)。 。