To show that in eosinophilic oesophagitis gastro-oesophageal reflux-induced epithelial barrier dysfunction facilitates passage of food-antigens through the epithelial barrier and subsequent increased exposure of antigens by dendritic cells activates…
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Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
- Allergic conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Oesophageal intercellular spaces are dilated in EoE patients compared to
healthy subjects.
- Mucosal permeability to small molecules is increased in EoE patients compared
to healthy subjects.
- Tissue impedance measurement is affected in EoE patients compared to healthy
subjects.
- Dilated intercellular spaces correlate with affected tissue impedance and
increased mucosal permeability to small molecules in EoE patients.
- Affected tissue impedance correlates with increased mucosal permeability to
small molecules in EoE patients.
- Numbers of oesophageal intraepithelial eosinophils are increased in EoE
patients compared to healthy subjects.
- Numbers of oesophageal intraepithelial mast cells are increased in EoE
patients compared to healthy subjects.
Secondary outcome
- Tissue impedance, dilation of intercellular spaces, increased mucosal
permeability to small molecules, and numbers of oesophageal intraepithelial
mast cells and eosinophils are reversible by 8 weeks administration of 40 mg
esomeprazole twice daily.
- The composition of inflammatory cells present in the esophageal biopsies
- The number of reflux episodes
Background summary
Eosinophilic oesophagitis (EoE) is a recently recognized disorder characterized
by symptoms of dysphagia and oesophageal food impaction. Long-term presence of
the disorder leads to fibrotic strictures and diffuse narrowing in the
oesophagus that require endoscopic dilatations.
The pathophysiology is largely unknown, a potential allergic pathway in the
pathophysiology of this disorder is suggested. Furthermore, it is reported that
patients with EoE are hypersensitive to acid. Current standard treatment uses
topical or systemic corticosteroids to suppress the immune system, a therapy
that is accompanied with various side-effects and therefore less suitable for
long-term use. The search for better therapy is complicated by the lack of
knowledge of the pathophysiology.
Recent data shows that in patients with EoE the periostin gene is overexpressed
and expression of the filaggrin gene is down regulated. Periostin is an
extracellular matrix molecule that regulates eosinophil adhesion while
filaggrin is a protein that is important for maintaining the epithelial
barrier. In the skin, it has been shown that a loss of function of filaggrin is
associated with increased skin permeability and susceptibility to atopic
dermatitis. It has been suggested that the atopic dermatitis is the result of
the increased penetration of antigens through the epithelium.
The esophageal biopsy specimens of EoE patient are characterized by a Th2-type
inflammatory process, with increased numbers of eosinophils, mast cells and
lymphocytes. The interplay between these cells remains largely unknown.
We hypothesize that in EoE a similar process of impaired epithelial barrier
function plays an important role. The impaired epithelial barrier could result
in a penetration of food antigens and subsequent uptake by epithelial cells
followed by activation of an inflammatory Th2 response. In gastro-oesophageal
reflux disease an impaired epithelial barrier function has been linked to
hypersensitivity to acid, and hence, this could explain the observed
hypersensitivity to acid in patients with eosinophilic oesophagitis as well.
Study objective
To show that in eosinophilic oesophagitis gastro-oesophageal reflux-induced
epithelial barrier dysfunction facilitates passage of food-antigens through the
epithelial barrier and subsequent increased exposure of antigens by dendritic
cells activates the Th2 immune response (increased numbers of eosinophils and
mast cells). Epithelial barrier dysfunction is defined as affected oesophageal
tissue impedance, dilated intercellular spaces and increased oesophageal
mucosal permeability.
Furthermore, we wish to widely investigate the composition of inflammatory
cells present in the esophageal biopsies of EoE patients and characterize them.
Study design
Prospective observational non-randomised study. 2 groups: EoE patients and
healthy subjects.
Study burden and risks
For this study patienten with EoE will receive once a pH-impedance measurement
en twice a gastroscopy (with biopsy taking). The risks consist of a bleeding or
perforation due to biopsy taking. These complications need to be treated
immediately, endoscopically or even surgically. The risk for these
complications, however, is small.
Preceding these interventions participating patients will be asked to stop the
use of topical corticosteroids. Participating patients will refrain from use of
topical corticosteroids for approximately 3 months.
Meibergdreef 9
1105 AZ Amsterdam
NL
Meibergdreef 9
1105 AZ Amsterdam
NL
Listed location countries
Age
Inclusion criteria
1. Previous diagnosis of eosinophilic oesophagitis confirmed by histopathology e.g. presence of >15 eosinophilic granulocytes per high power field in mid-oesophageal biopsies before the start of any therapy
2. Written informed consent
3. Age 18 * 75 years
Exclusion criteria
1. Inability to stop topical corticosteroids
2. Inability to stop PPI, H2-receptor antagonist or prokinetic drug for 8 weeks
3. Use of systemic corticosteroids, leukotriene inhibitors, or monoclonal antibodies, in the 2 month period preceding the study
4. Use of oral anticoagulants
5. Use of NSAIDs
6. History of peptic ulcer disease
7. History of Barrett*s oesophagus
8. History of GI cancer
9. History of GI tract surgery (except appendectomy)
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
Register | ID |
---|---|
CCMO | NL36704.018.11 |
OMON | NL-OMON28827 |