A Randomized Double Blind Placebo Controlled Study of the Effect of Swallowed Beclomethasone Dipropionate on Inflammatory Markers in Adult Patients With Eosinophilic Esophagitis

EoE is an increasingly recognized clinicopathological diagnosis, characterized by a marked
accumulation of eosinophils in the esophageal mucosa.The presence of eosinophils and
association of the disease with food allergy and allergic rhinitis suggests an atopic
disease. Allergic diseases are associated with T-helper 2 lymphocytes (TH2) predominant
cytokines such as interleukins 4, 5, 13 (IL4, IL5, IL13), which are known to induce IgE
synthesis and promote eosinophilic infiltration. Granulocyte-Monocyte Colony Stimulating
Factor (GM-CSF) and Transforming Growth Factor (TGF) - beta are cytokines which are
associated with many eosinophilic disorders. Swallowed steroid is a conventional treatment
that has been shown to improve symptoms and decrease number of eosinophils in the esophagus
in patients with EoE. However, no studies have investigated the effect of swallowed steroid
on markers of TH2 inflammation in adult patients with EoE.Currently repeated endoscopic
biopsy of esophagus is the only tool to monitor response to treatment. Serum ultra-
sensitive CRP is a non-invasive marker of inflammation in cardiovascular and
gastrointestinal disorders. This study proposes to investigate the correlation of disease
activity with this potential marker of inflammation in adult patients with EoE which has not
been previously studied.

Specific Aim #1: To measure the baseline level of a proposed panel of inflammatory markers:
serum ultra-sensitive CRP and peripheral eosinophils, as well as tissue eosinophils, mast
cells, CD4 cells, IL-4, IL-5, IL-13, GM-CSF and TGF-beta in the esophagus in adult patients
with eosinophilic esophagitis.

Specific Aim #2: To determine the impact of 8 week course of treatment with swallowed
beclomethasone on the levels of the inflammatory markers measured in Specific Aim #1.

Specific Aim #3: To determine the correlation between the levels of the proposed panel of
inflammatory markers and symptoms of EoE before and after 8 weeks of treatment with
swallowed beclomethasone.

Inclusion Criteria:

- Male or female subjects 18 years of age or older with biopsy proven diagnosis of EoE.

- Subjects who are able and willing to provide consent for repeat EGDs with esophageal
biopsies, and blood work as per study protocol.

Exclusion criteria:

- Subjects with suspected or proven inflammatory bowel disease, malignancy, and
collagen-vascular disease.

- Subjects who have used oral, inhaled or swallowed corticosteroids in the past 3
months.

- Subjects who are pregnant or breastfeeding

- Subjects who are not able to swallow beclomethasone or are intolerant to the
medication.

- Subjects with history of ischemic heart disease, diabetes and dyslipidemia unless
they have been stable in the last six months.