Ignite Creation Date:
2024-05-06 @ 7:50 PM
Last Modification Date:
2024-10-26 @ 3:15 PM
Study NCT ID:
NCT06159218
Status:
RECRUITING
Last Update Posted:
2023-12-06
First Post:
2022-11-24
Brief Title:
Eosinophilic Oesophagitis Assessment With String Testing
Sponsor:
St Georges University of London
Organization:
St Georges University of London
Study Overview
Official Title:
Eosinophil Associated Proteins and Microbiome Profiling in Adults With Eosinophilic Oesophagitis at a Single UK Tertiary Centre
Status:
RECRUITING
Status Verified Date:
2023-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
EoEAST
Brief Summary:
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
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
Detailed Description:
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 100000 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 eosHPF 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 seafoodshellfish 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
Gastroscopy involves placing a thin flexible camera into a patients mouth and advancing it to the oesophagus stomach and duodenum The procedure takes approximately 5 minutes during which biopsy forceps are placed through a 28mm channel on the standard gastroscope to obtain oesophageal mucosal biopsies for histological analysis Although topical anaesthetic may be applied to the back of the throat and intravenous sedation given for many patients gastroscopy remains an unpleasant and daunting experience Transnasal endoscopy TNE has more recently been developed and potentially offers patients a more comfortable procedure due to the reduced diameter of the gastroscope but due to the need for lifelong surveillance there has been a move for even less invasive and less costly methods
The GI string test EnteroTestTM was first developed in 1970 for sampling microorganisms from the small intestine The original test involved swallowing a small weighted gelatin capsule to which a string was attached and the other end taped to the patients cheek The capsule reaches the duodenum where it detaches and is excreted naturally and the string left in situ overnight The string is then pulled out via the mouth and can be analysed Over the years it has been used to analyse biliary composition culture intestinal tuberculosis and profile the distinct microbiome in the oesophagus using 16S rRNA gene sequencing as accurately as with mucosal biopsy
The potential for oesophageal string testing EST to monitor EoE activity has been suggested by a previous study using an overnight swallowed string test in 41 children correlated with EoE activity on biopsy which could distinguish between active EoE treated EoE GORD and normal oesophagus using measured ESGP eosinophil secondary granule proteins - including major basic protein 1 MBP1 esosinophil peroxidase EPX eosinophil derived neurotoxin EDN and eosinophil cationic protein ECP Also measured was the Chacot-Leyden crystal proteingalectin-10 CLCGal-10 which is a primary cytosolic protein but is also present in the eosinophils primary coreless granule Each granule-associated protein carries different biochemical and functional properties relevant to proposed pathogenic mechanisms for oesophageal dysfunction and remodelling in EoE These biomarkers were found to be elevated uniquely in active EoE compared to treated EoE GORD and normal controls
Another previous study performed a one hour string test on 134 people with EoE or healthy control comparing levels of eosinophil associated protein EAP including eotaxin-2 Eot2 eotaxin-3 Eot3 and MBP on EST to mucosal biopsy Ackerman showed that these EST-captured eosinophil-associated biomarkers were proportionate on EST and mucosal biopsy levels and also correlated with EoE activity as defined by mucosal eosinophil counts These proteins on EST therefore had excellent sensitivity and specificity for identifying active EoE They also surveyed patients and 92 adults preferred the EST over gastroscopy to monitor their EoE
Whilst these studies have shown the potential of intraluminal oesophageal biomarkers to reflect EoE activity additional research is required to further characterise their relation to disease activity correlation with symptoms and response to different treatments which has not yet been described in the literature This knowledge may improve our understanding of the pathogenesis of EoE and lead to new therapeutic targets in future as well as reduce the need for surveillance endoscopy in EoE which would be safer and more convenient for patients and offer cost savings for healthcare resources
The role of the microbiome is increasingly been appreciated in the development of immune mediated disease such as EoE yet to date there are only a handful of studies on the oesophageal microbiome finding distinct changes in EoE compared to GORD adenocarcinoma and healthy patients Further research in this area would be interesting to establish if the microbiome is different in active EoE vs remission and how this may affect disease severity and symptoms which again may lead to new therapeutic targets in future
In addition it is not known whether people with EoE have altered sensitivity in their oesophagus as part of the remodelling from the chronic inflammatory process If sensation is increased this could lead to increased symptoms and if it is reduced then this coud lead to undiagnosed conditions including strictures and GORD The calcitonin gene related peptide has recently been shown to be a marker of oesophageal sensory nerves and has been shown to be closer to the oesophageal lumen in oesophageal hypersensitivity however its relation to EoE has not yet been examined
In this study the investigators will sample oesophageal biomarkers and the microbiome from adults with EoE using a 30 minute string test which will be performed on the same day as their routine gastroscopy an addition to validated symptom questionnaires The investigators will repeat the string test after treatment courses with PPI budesonide or dietary elimination alongside their routine gastroscopy During their gastroscopy the investigators will also take biopsies to check for the density and positioning of CGRP to see if this is different in active and inactive EoE The aim is to correlate biomarkers CGRP and microbiome with endoscopic EoE activity and symptoms to assess for changes in response to different treatments and again may provide further insight into disease pathogenesis and lead to new therapeutic targets in future
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 eosHPF 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 seafoodshellfish 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
Gastroscopy involves placing a thin flexible camera into a patients mouth and advancing it to the oesophagus stomach and duodenum The procedure takes approximately 5 minutes during which biopsy forceps are placed through a 28mm channel on the standard gastroscope to obtain oesophageal mucosal biopsies for histological analysis Although topical anaesthetic may be applied to the back of the throat and intravenous sedation given for many patients gastroscopy remains an unpleasant and daunting experience Transnasal endoscopy TNE has more recently been developed and potentially offers patients a more comfortable procedure due to the reduced diameter of the gastroscope but due to the need for lifelong surveillance there has been a move for even less invasive and less costly methods
The GI string test EnteroTestTM was first developed in 1970 for sampling microorganisms from the small intestine The original test involved swallowing a small weighted gelatin capsule to which a string was attached and the other end taped to the patients cheek The capsule reaches the duodenum where it detaches and is excreted naturally and the string left in situ overnight The string is then pulled out via the mouth and can be analysed Over the years it has been used to analyse biliary composition culture intestinal tuberculosis and profile the distinct microbiome in the oesophagus using 16S rRNA gene sequencing as accurately as with mucosal biopsy
The potential for oesophageal string testing EST to monitor EoE activity has been suggested by a previous study using an overnight swallowed string test in 41 children correlated with EoE activity on biopsy which could distinguish between active EoE treated EoE GORD and normal oesophagus using measured ESGP eosinophil secondary granule proteins - including major basic protein 1 MBP1 esosinophil peroxidase EPX eosinophil derived neurotoxin EDN and eosinophil cationic protein ECP Also measured was the Chacot-Leyden crystal proteingalectin-10 CLCGal-10 which is a primary cytosolic protein but is also present in the eosinophils primary coreless granule Each granule-associated protein carries different biochemical and functional properties relevant to proposed pathogenic mechanisms for oesophageal dysfunction and remodelling in EoE These biomarkers were found to be elevated uniquely in active EoE compared to treated EoE GORD and normal controls
Another previous study performed a one hour string test on 134 people with EoE or healthy control comparing levels of eosinophil associated protein EAP including eotaxin-2 Eot2 eotaxin-3 Eot3 and MBP on EST to mucosal biopsy Ackerman showed that these EST-captured eosinophil-associated biomarkers were proportionate on EST and mucosal biopsy levels and also correlated with EoE activity as defined by mucosal eosinophil counts These proteins on EST therefore had excellent sensitivity and specificity for identifying active EoE They also surveyed patients and 92 adults preferred the EST over gastroscopy to monitor their EoE
Whilst these studies have shown the potential of intraluminal oesophageal biomarkers to reflect EoE activity additional research is required to further characterise their relation to disease activity correlation with symptoms and response to different treatments which has not yet been described in the literature This knowledge may improve our understanding of the pathogenesis of EoE and lead to new therapeutic targets in future as well as reduce the need for surveillance endoscopy in EoE which would be safer and more convenient for patients and offer cost savings for healthcare resources
The role of the microbiome is increasingly been appreciated in the development of immune mediated disease such as EoE yet to date there are only a handful of studies on the oesophageal microbiome finding distinct changes in EoE compared to GORD adenocarcinoma and healthy patients Further research in this area would be interesting to establish if the microbiome is different in active EoE vs remission and how this may affect disease severity and symptoms which again may lead to new therapeutic targets in future
In addition it is not known whether people with EoE have altered sensitivity in their oesophagus as part of the remodelling from the chronic inflammatory process If sensation is increased this could lead to increased symptoms and if it is reduced then this coud lead to undiagnosed conditions including strictures and GORD The calcitonin gene related peptide has recently been shown to be a marker of oesophageal sensory nerves and has been shown to be closer to the oesophageal lumen in oesophageal hypersensitivity however its relation to EoE has not yet been examined
In this study the investigators will sample oesophageal biomarkers and the microbiome from adults with EoE using a 30 minute string test which will be performed on the same day as their routine gastroscopy an addition to validated symptom questionnaires The investigators will repeat the string test after treatment courses with PPI budesonide or dietary elimination alongside their routine gastroscopy During their gastroscopy the investigators will also take biopsies to check for the density and positioning of CGRP to see if this is different in active and inactive EoE The aim is to correlate biomarkers CGRP and microbiome with endoscopic EoE activity and symptoms to assess for changes in response to different treatments and again may provide further insight into disease pathogenesis and lead to new therapeutic targets in future
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| IRAS | OTHER | 303427 | None |