Eosinophil Associated Proteins and Microbiome Profiling in Adults With Eosinophilic Oesophagitis at a Single UK Tertiary Centre
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- How does the density of calcitonin gene related peptide (CGRP) in the oesophageal mucosal biopsy change after treatment for EoE?
研究概览
简要总结
Eosinophilic oesophagitis (EoE) is an inflammatory condition of the oesophagus (food pipe) that can lead to difficulty swallowing and to food to getting stuck and has become increasingly common over the past 40 years.
EoE is triggered by a protein in the diet but alterations to the types of bacteria (microbiome) in the oesophagus may also be involved. EoE is diagnosed with gastroscopy (a thin camera test via the mouth) where 6 tiny samples (biopsies) are taken. Treatment is either with removing food groups from the diet or medications including steroids (budesonide) or a proton pump inhibitor (PPI, omeprazole). The aim is to improve symptoms and to stop scar tissue forming that can cause food to get stuck.
Patients with EoE will need to undergo many gastroscopies over their life, which even with sedation can be a daunting experience. There has been research into less invasive tests and two previous studies have shown that a thin swallowed string may be able to detect substances (biomarkers) that indicate how severe the EoE is. These studies were small and it is not known how the biomarkers change with different treatments or how well they relate to symptoms and findings with endoscopy.
In this study the investigators will ask adults with EoE to swallow a thin string made of rayon for 30 minutes, with one end taped to the cheek, which the investigators will analyse for biomarkers and bacteria, on the same day as their routine gastroscopy and also perform a symptom survey. The investigators will also take an extra 2 biopsies to analyse the nerves which may explain why some patients have more symptoms than others. The investigators will repeat the string test on their next endoscopy, to assess what the changes have been in response to their treatments. These findings may improve understanding on how to monitor EoE in less invasive ways in future.
详细描述
Eosinophilic oesophagitis (EoE) is a chronic progressive inflammatory condition of the oesophagus first described in 1978 but not recognised as distinct diagnosis until 1993, affecting both children and adults. It is characterised by eosinophilic infiltration of the oesophageal epithelium and can lead to difficulty swallowing, oesophageal strictures, food bolus obstruction, and symptoms mimicking gastro-oesophageal reflux disease (GORD). 23% adults with dysphagia and 50% with food bolus obstruction are diagnosed with EoE, meaning it is a common condition encountered by Gastroenterologists. Recent systematic reviews have estimated that EoE has a pooled prevalence of 28-34 per 100,000 population, but the incidence has risen remarkably over the past four decades.
EoE can occur at any age, with a rising incidence in children and adults aged 30-50 years and studies have shown that it can significantly impact on health related quality of life by impairing social and psychological functioning. It is more common in males and in those with allergic conditions such as asthma, eczema and rhinitis, suggesting a food or aeroallergen trigger. Diagnosis is obtained by gastroscopy with a minimum of six oesophageal biopsies recommended by international guidelines, due to its potentially patchy distribution. Hallmark endoscopic appearances of the oesophagus have been described and include oesophageal rings, longitudinal furrows, oedema, exudate, and narrowing. Oesophageal biopsies must show > 15 eosinophils (eos) per high powered field (HPF) infiltrating the oesophageal mucosa, as to not be mistaken with other conditions such as GORD which may also exhibit eosinophilic infiltration but at lower numbers. Other histological features include eosinophil micro-abscesses, basal zone hyperplasia, dilated intercellular spaces, eosinophil surface layering, papillary elongation and lamina propria fibrosis.
Once a diagnosis has been made, treatment of EoE is with food elimination diets, proton pump inhibitors (PPI), or topical glucocorticoids, such as budesonide orodispersible tablet (BOT). In a small subgroup of patients, immunomodulatory drugs such as azathioprine or 6-mercaptopurine might be required, and research is ongoing into monoclonal antibody therapy. The aim of treatment, as described in recent European and American Gastroenterological Association (AGA) and Joint Task Force on Allergy Immunology Practice Parameters (JTF) guidelines, is to alleviate symptoms, prevent stricture formation and achieve histological remission with < 15 eos/HPF infiltration.
Previous studies have shown that PPI may induce remission in 42% patients. Budesonide orodispersible table (BOT) may induce remission in 85% patients, but can be associated with the side effect of candidiasis in up to 10% patients. An empiric 6-food (dairy, wheat, soy, eggs, nuts, and seafood/shellfish) elimination diet induces histological remission in around 75% of patients, whereas a 4-food elimination diet (dairy, wheat, soy, and egg) induced histological remission in around 50% patients, and a 2-food elimination diet (dairy and wheat) may be effective for 40% patients. Elemental diet (amino acids) induces histological remission in 90% of patients but is impractical and only recommended for consideration after failure of medical therapy or elimination diets. Prolonged avoidance of dietary triggers may lead to drug-free sustained clinical and histological remission. Once a stricture has developed then endoscopic balloon dilatation may be required and can improve dysphagia in up to 75% of adults with oesophageal strictures, and is relatively safe with a perforation rate of only 1%, but has no effect on the underlying inflammatory process.
Systematic review with meta-analysis found no statistical difference between PPI and BOT, however there are few head to head studies comparing the treatments and long term evidence for BOT is still lacking; indicating the need for further prospective studies. European guidelines therefore currently do not favour one treatment over another and state that the choice of therapy should be individually discussed with the patient and may be interchangeable over time. Treatment effectiveness should be assessed with repeat gastroscopy with oesophageal biopsies after 6-12 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 90 Years(Adult, Older Adult)
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patient under the care of St George's University Hospital NHS Foundation Trust, London
- •Diagnosis of EoE as defined by endoscopy with mucosal biopsy showing >15 eos/HPF
- •Male or Female
- •Age 18 to 90
排除标准
- •Patients < 18 years old or >90 years old
- •Patients with significant medical co-morbidities
- •Patients unable to provide consent for study participation
- •Patients who have had complications from their endoscopy or EoE treatment
- •Patients who have previously undergone oesophageal surgery
结局指标
主要结局
How does the density of calcitonin gene related peptide (CGRP) in the oesophageal mucosal biopsy change after treatment for EoE?
时间窗: 12 weeks
Assessment of change in density of CGRP in mucosa after treatment for EoE
Do eosinophil associated protein (EAP) biomarkers detected with string testing correlate with peak eosinophil count (eos/HPF) on endoscopic mucosal biopsy in adults with eosinophilic oesophagitis (EoE)?
时间窗: 12 weeks
Measurement of string biomarker levels in comparison to mucosal eosinophil counts
How does the oesophageal microbiome, sampled with string testing, change after treatment for EoE?
时间窗: 12 weeks
Measurement of bacterial abundance (sequences per sample) on string testing
次要结局
- How do EAP detected with string testing change in response to treatments for EoE?(12 weeks)
- How does the oesophageal microbiome, sampled with string testing differ in EoE treatments?(12 weeeks)
