The Effect of Acute Tryptophan Depletion (ATD) on Esophageal Sensitivity in Healthy Volunteers: a Randomized, Single-blind, Placebo-controlled Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 2
- 主要终点
- Measurement of changes in esophageal sensitivity after acute tryptophan depletion assessed by multimodal esophageal stimulation protocol
研究概览
简要总结
Esophageal hypersensitivity is considered an important pathophysiological mechanism in patients suffering form non-erosive gastro-esophageal reflux disease. Serotonin (5-HT) is predominantly found in the central nervous system and in the gastro-intestinal (GI) tract. 5-HT plays a major role in the regulation of GI secretion, motility and sensitivity, and has been associated with emotion regulation. Acute tryptophan depletion (ATD) temporarily reduces the availability of tryptophan (TRP), thereby decreasing central and peripheral 5-HT synthesis. From previous studies, ATD is known to affect GI physiology and enhance visceral pain perception in the colon. The aim of the study was to investigate the effect of ATD on esophageal sensitivity in healthy volunteers (HV).
Esophageal multimodal sensitivity was assessed after intragastric infusion of an amino-acid mixture (AA-mix) containing 15 AAs with TRP (control condition) or without TRP (ATD condition). After an incubation period of 5 hours, a probe with a polyurethane bag was positioned in the distal esophagus. Thermal (recirculating a heated saline solution through the bag), mechanical (increasing bag volume), electrical (2 stimulation electrodes) and chemical sensitivity (modified Bernstein) were tested and at 3 time points blood samples were collected for biochemical analysis. General mood was assessed by the Positive and Negative Affect Schedule (PANAS) and the State-Trait Anxiety Inventory (STAI) questionnaires.
详细描述
- INTRODUCTION Gastro-esophageal reflux disease (GERD), defined as the presence of symptoms or lesions that can be attributed to reflux of gastric contents into the esophagus, is an increasingly prevalent condition in Western societies. Typical reflux symptoms are heartburn and regurgitation, but GERD can manifest itself through a variety of esophageal and extra-esophageal (atypical) symptoms (e.g. chronic cough).
In humans, pain is a multimodal experience composed of sensory, physiological and psychological aspects. In order to mimic the clinical situation, experimental models should be based on multimodal 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 persisting symptoms in spite of proton pump inhibitor (PPI) treatment (refractory GERD), ongoing weakly acidic reflux is well established as the main underlying factor.
The basis for symptom generation during weakly-acidic reflux events remains to be elucidated, 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 esophageal symptom perception. This is suggested by the reflux parameters that are usual within the physiological number during PPI therapy. Also, previous studies demonstrated that refractory GERD patients on PPI therapy have increased visceral hypersensitivity for thermal, chemical and mechanical esophageal stimulation compared to healthy subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
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
- •Age between 18 and 60 years old
排除标准
- •history of psychiatric disease or a positive first degree psychiatric family history,
- •pregnancy or lactation,
- •concomitant administration of any centrally activating medication
- •medication affecting esophageal motility,
- •significant co-morbidities (neuromuscular, 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
- •During the last two weeks before the study, the volunteers should be free from medication, except for oral contraceptives.
结局指标
主要结局
Measurement of changes in esophageal sensitivity after acute tryptophan depletion assessed by multimodal esophageal stimulation protocol
时间窗: 2 sessions per HV with at least one week interval, duration of each session: approximately 7 hours. Temperature stimulation: 30 minutes
Investigation of the effect of acute tryptophan depletion on esophageal sensitivity to multimodal stimulation in a group of healthy volunteers. This will be assessed by comparing the Temperature values (°C) of the stimulation tests between the placebo and acute tryptophan depletion condition to see if tryptophan depletion affects the sensitivity to increasing temperature.
Measurement of changes in esophageal sensitivity after acute tryptophan depletion
时间窗: 2 sessions per HV with at least one week interval, duration of each session: approximately 7 hours. Chemical stimulation: 30 minutes
Investigation of the effect of acute tryptophan depletion on esophageal sensitivity to multimodal stimulation in a group of healthy volunteers. This will be assessed by comparing the volume of infused acid (ml) of the stimulation tests between the placebo and acute tryptophan depletion condition to see if tryptophan depletion affects the sensitivity to acid infusion.
次要结局
未报告次要终点