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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01016223
Recruitment Status : Completed
First Posted : November 19, 2009
Last Update Posted : November 30, 2012
Information provided by (Responsible Party):
Gisoo Ghaffari, Penn State University

Brief 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.

Condition or disease Intervention/treatment Phase
Eosinophilic Esophagitis Drug: Beclomethasone dipropionate Drug: placebo Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Study Start Date : March 2010
Actual Primary Completion Date : July 2012
Actual Study Completion Date : October 2012

Arm Intervention/treatment
Active Comparator: Beclomethasone dipropionate inhaler Drug: Beclomethasone dipropionate
Beclomethasone dipropionate 80 mcg two puffs twice daily for 8 weeks

Placebo Comparator: Matched inhaler Drug: placebo
Matched placebo swallowed two puffs twice daily

Primary Outcome Measures :
  1. Symptom improvement [ Time Frame: 5 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01016223

United States, Pennsylvania
Penn State Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Sponsors and Collaborators
Penn State University
Principal Investigator: GISOO GHAFFARI, MD Penn State College of Medicine Hershey Medical Center

Responsible Party: Gisoo Ghaffari, Assistant professor of Medicine, Penn State University Identifier: NCT01016223     History of Changes
Other Study ID Numbers: 32508
First Posted: November 19, 2009    Key Record Dates
Last Update Posted: November 30, 2012
Last Verified: November 2012

Keywords provided by Gisoo Ghaffari, Penn State University:
Eosinophilic esophagitis
Ultrasensitive CRP

Additional relevant MeSH terms:
Eosinophilic Esophagitis
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Leukocyte Disorders
Hematologic Diseases
Hypersensitivity, Immediate
Immune System Diseases
Anti-Inflammatory Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents