Clinical trial NCT00275561: Topical Steroid Treatment for Eosinophilic Esophagitis
Official title: A Randomized Placebo-controlled Trial of Swallowed Fluticasone in Treatment of Eosinophilic Esophagitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Eosinophilic Esophagitis
Keywords: Eosinophilic Esophagitis
Fluticasone
Dysphagia
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2006-01-12
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Complete Response to Dysphagia
timeFrame: 2 weeks
Secondary outcomes:
measure: Number of Participants With Partial or Complete Response to Dysphagia
timeFrame: 2 weeks
measure: Number of Participants With Complete Histologic Response
timeFrame: 2 weeks
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Jeffrey A. Alexander, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.