The Effect of Corticotrophin-releasing Hormone (CRH) on Esophageal Motility in Healthy Volunteers
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Changes in esophageal contractile properties after Intravenous CRH administration in Healthy Volunteers
研究概览
简要总结
Stress is well known to affect visceral sensitivity and gastrointestinal function in general. A majority of patients with gastroesophageal reflux disease (GERD) report stress as an important factor triggering symptom exacerbation. A real-life stressor could exacerbate heartburn symptoms in GERD patients by enhancing perceptual response to esophageal acid exposure. In Irritable Bowel Syndrome (IBS) patients, visceral hypersensitivity is a major pathophysiological mechanism and stress is shown to trigger or exacerbate symptoms.
A possible mechanism of stress-induced visceral sensitivity could be the barrier dysfunction. Indeed, in a study performed by our group, in human, an acute psychological stressor induces hyperpermeability in a mast cell dependent fashion and exogenous peripheral corticotrophin-releasing hormone (CRH) recapitulated its effects on barrier function. This increase in intestinal permeability is a phenomenon which appears as a prerequisite for visceral hypersensitivity. Furthermore, few studies indicate that human intestinal motility is probably modulated by CRH. It has been shown that the brain-gut axis in IBS patients has an exaggerated response to CRH.To our knowledge, the acute effect of exogenous CRH on esophageal motility has not been studied before.
详细描述
- INTRODUCTION Gastro-esophageal reflux disease (GERD), defined as the presence of symptoms or lesions that can be attributed to the reflux of gastric contents into the esophagus, is an increasingly prevalent condition in Western societies. The most typical symptoms are heartburn and regurgitation, but GERD can manifest itself through a variety of esophageal and extra-esophageal symptoms (e.g. chronic cough).
In humans, pain is a multimodal experience composted of sensory, physiological and psychological aspects. In order to mimic the clinical situation, experimental models should be based on testing regimens in which different receptors and central nervous system mechanisms are activated.
Advances in esophageal sensory stimulation have established that both typical and atypical symptoms may not only arise from acid reflux, but also from reflux events with less acidic pH (pH 4-7). In GERD patients with symptoms that persist in spite of acid suppressive therapy, ongoing weakly-acidic and non-acid reflux is now well established as the main underlying factor.
The basis for symptom generation during weakly-acidic reflux events remains to be determined, but acid sensitivity in the pH range 4-7, mechanical distention (enhanced by air in the refluxate), sensitivity to other chemical factors (e.g. bile) and esophageal hypersensitivity to physiological levels of reflux have all been proposed.
The investigators speculate that visceral hypersensitivity plays an important role in symptom perception. This is suggested by the reflux parameters that are usual within the physiological number during proton pump inhibitor (PPI) therapy. Also, our group previously demonstrated that refractory GERD patients have increased visceral hypersensitivity for thermal, chemical and mechanical esophageal stimulation compared to healthy volunteers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •No history of gastrointestinal symptoms or complaints.
排除标准
- •History of allergic reaction to CRH, atopy (eczema, asthma, food allergies, allergic rhinoconjunctivitis) or multiple allergies to several drugs
- •Pregnancy or lactation
- •Concomitant administration of monoamine oxidase inhibitors (MAOI), verapamil or diltiazem or medication affecting esophageal motility
- •Significant co-morbidities (neuromuscular, psychiatric, cardiovascular, pulmonary, endocrine, autoimmune, renal and hepatic)
- •Prior history of esophageal, Ear Nose and Throat, or gastric surgery or endoscopic anti-reflux procedure
- •History of gastrointestinal disease and first degree relatives with Crohn's disease or celiac disease.
- •During the last two weeks before the study the volunteers should be free from medication, except for oral contraceptives
研究组 & 干预措施
CRH condition
All HV first underwent a baseline manometry measurement. After 30 minutes, an intravenous CRH injection was done. The same measurement was repeated but now with CRH administered.
干预措施: CRH (Drug)
结局指标
主要结局
Changes in esophageal contractile properties after Intravenous CRH administration in Healthy Volunteers
时间窗: approximately 2 hours study period, effect of CRH will be evaluated 30 minutes after the administration
The investigators will evaluate if the administration of intravenous CRH alters esophageal contractile properties. Esophageal contractile properties are measured by high resolution manometry (HRM). HRM measurements in the esophagus will be performed before and after CRH administration. The investigators will compare 3 HRM parameters (distal contractile integral (mmHg.s.cm), intrabolus pressure (mmHg), LES relaxation (mmHg)) before and after the administration of CRH and assess the number of HV in which these 3 parameters are altered after CRH administration to be able to report changes in contractile properties of the esophagus.
次要结局
未报告次要终点
研究者
Prof Dr Jan Tack
Prof. Dr., MD, PhD
Universitaire Ziekenhuizen KU Leuven