Topical Steroid Treatment for Eosinophilic Esophagitis

Eosinophilic Esophagitis Clinical Trial

Official title:

A Randomized Placebo-controlled Trial of Swallowed Fluticasone in Treatment of Eosinophilic Esophagitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00275561
• Other study ID #: 1488-05
• Status: Completed
• Phase: Phase 2
• First received: January 10, 2006
• Last updated: May 1, 2012
• Start date: November 2005
• Est. completion date: April 2010

Study information

• Verified date: May 2012
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

This was a randomized controlled trial of swallowed fluticasone vs. placebo for eosinophilic esophagitis. Eosinophilic esophagitis is an inflammatory condition in which the wall of the esophagus becomes filled with large numbers of eosinophils, a type of white blood cell. Patients who have this condition have difficulty in swallowing (dysphagia) solid food.

Prior to treatment the patients had biopsies of their esophagus and took questionnaires regarding their symptoms. Treatment was given for 6 weeks, after which biopsies were taken from the esophagus to measure any changes in the tissue from before treatment. The primary endpoint was improvement in dysphagia as measured by the validated Mayo Dysphagia Questionaire. Secondary outcomes included partial symptom response, and histologic (tissue) response to treatment.

Description:

This was a double-blind randomized placebo controlled trial to evaluate the effect of aerosolized fluticasone therapy on symptomatic dysphagia and histologic eosinophilia in adults newly diagnosed with eosinophilic esophagitis (EoE). Participants were randomized to receive aerosolized swallowed fluticasone 880 mcg bid or placebo inhaler swallowed bid for 6 weeks.

Four mid esophageal biopsies were obtained from 10 cm above the squamo-columnar junction; then formalin-fixed and stained with hematoxylin and eosin. All esophageal biopsies were read and scored by a single expert gastrointestinal pathologist. The formalin-fixed paraffin-embedded esophageal biopsies were retrieved and underwent standard major basic protein (MBP) immunofluorescence staining. All special stain slides were then read and scored by another pathologist. 24-hour urine was collected for free cortisol by the standard technique. The original endoscopy was performed before the patient was enrolled in the trial by standard clinical technique. The endoscopy post treatment was done in the clinical research unit by the principal investigator.

Patients kept compliance logs that were reviewed at phone interviews at 2 and 4 weeks time and at the end of study evaluation. Ninety percent compliance was required for study inclusion.

At the end of 6 weeks, a 24-hour urine cortisol was done, and patients underwent a repeat endoscopy while still on treatment. Mid-esophageal biopsies were obtained and evaluated for eosinophil density and mast cell degranulation. At this visit the patients returned dysphagia and side effects questionnaires.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: April 2010
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• > 20 eosinophils / hpf on biopsies from mid esophagus (hpf = high-powered field)

• Abnormal dysphagia questionnaire (question 1a "yes", question 1c > "moderate" and question 2 > "less than once a week") on Mayo Dysphagia Questionnaire.

Exclusion Criteria:

• Clinical evidence of infectious process potentially contributing to dysphagia (e.g., candidiasis, cytomegalovirus, herpes)

• Systemic or topical steroid therapy for any reason over the past 3 months

• Previous steroid treatment for Eosinophilic Esophagitis

• Intolerance to steroid therapy in the past

• Other cause of dysphagia identified at endoscopy (e.g., reflux esophagitis, stricture, web, ring, achalasia, esophageal neoplasm)

• Dilatation of esophagus at time of index endoscopy

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Eosinophilic Esophagitis
• Esophagitis

Intervention

Drug:
• Fluticasone
Aerosolized swallowed fluticasone 880 mg twice a day
• Placebo
Placebo inhaler swallowed twice a day for 6 weeks

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

References & Publications (1)

McElhiney J, Lohse MR, Arora AS, Peloquin JM, Geno DM, Kuntz MM, Enders FB, Fredericksen M, Abdalla AA, Khan Y, Talley NJ, Diehl NN, Beebe TJ, Harris AM, Farrugia G, Graner DE, Murray JA, Locke GR 3rd, Grothe RM, Crowell MD, Francis DL, Grudell AM, Dabade T, Ramirez A, Alkhatib M, Alexander JA, Kimber J, Prasad G, Zinsmeister AR, Romero Y. The Mayo Dysphagia Questionnaire-30: documentation of reliability and validity of a tool for interventional trials in adults with esophageal disease. Dysphagia. 2010 Sep;25(3):221-30. doi: 10.1007/s00455-009-9246-8. Epub 2009 Oct 24. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Complete Response to Dysphagia	Measured by the Mayo Dysphagia Questionnaire, a validated 28 item instrument; 0=no dysphagia, higher levels indicate greater dysphagia severity. A complete symptom response was defined as an answer of "no" to the question "In the past 2 weeks, have you had trouble swallowing, not associated with other cold symptoms (such as strep throat or mono)?"	2 weeks	No
Secondary	Number of Participants With Partial or Complete Response to Dysphagia	Measured by the Mayo Dysphagia Questionnaire, a validated 28 item instrument; 0=no dysphagia, higher levels indicate greater dysphagia severity. A complete symptom response was defined as an answer of "no" to the question "In the past 2 weeks, have you had trouble swallowing, not associated with other cold symptoms (such as strep throat or mono)?" A partial symptom response was defined as an answer of yes to the above question and a decrease in severity of at least 2 levels, or a decrease in frequency of at least 1 level.	2 weeks	No
Secondary	Number of Participants With Complete Histologic Response	A complete histologic response was defined as >90% decrease in mean eosinophil count/high powered field	2 weeks	No

External Links

•   Mayo Clinic Clinical Trials