A Randomized Double Blind Placebo Controlled Study of the Effect of Swallowed Beclomethasone Dipropionate on Inflammatory Markers in Adult Patients With Eosinophilic Esophagitis
Condition: Eosinophilic Esophagitis
MeSH terms: Esophagitis; Eosinophilic Esophagitis
Study type: Interventional
Phase: Phase 1

Summary: 
      The investigators hypothesize that swallowed beclomethasone leads not only to improvement of
      symptoms and decreased number of eosinophils in esophageal mucosa, but also to a decrease in
      other markers of tissue inflammation like mast cells, CD4+ T lymphocytes, IL4, IL-5, IL13,
      GM-CSF and TGF-beta as well as serum ultra-sensitive C-Reactive Protein (CRP). The
      investigators aim to characterize the response of esophageal inflammation to swallowed
      topical glucocorticoids, and identify biomarkers to assess response to treatment.

      This research will elucidate the effect of treatment with beclomethasone on various
      inflammatory markers in EoE, which is currently not well-understood. This work will explore
      the pathophysiology of EoE, and has the potential to find a non-invasive biomarker such as
      high-sensitivity CRP that can be used to monitor the response to treatment.
    

Detailed description: 
      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.
    

Intervention name(s): Beclomethasone dipropionate; placebo
Intervention type(s): Drug; Drug
Intervention description(s): Beclomethasone dipropionate 80 mcg two puffs twice daily for 8 weeks; Matched placebo swallowed two puffs twice daily
Intervention MeSH terms: Beclomethasone
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Keywords: Eosinophilic esophagitis; Beclomethasone; Ultrasensitive CRP