Clinical trial NCT00728481: The Role Of Gastroesophageal Reflux Disease (GERD) in Eosinophilic Esophagitis
Official title: The Role Of Gastroesophageal Reflux Disease (GERD) in Eosinophilic Esophagitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Eosinophilic Esophagitis
Gastroesophageal Reflux Disease
EE
GERD
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2008-08-05
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary aim of this study was to determine the proportion of patients with esophageal eosinophilic infiltration that have objective (measurable) evidence of gastroesophageal reflux disease (GERD).

This study was also done to see if patients that have eosinophilic esophagitis (EE) and GERD would receive relief from taking the medication Nexium or a steroid called Pulmicort.

The study also evaluated the accuracy of pH monitoring (acid exposure) within the esophagus as a predictor of endoscopic, histological and symptomatic response in patients with EE.

Detailed description: Hypotheses:

1. There is a subset of patients with the diagnosis of EE who also have GERD.
2. Patients with both EE and GERD will respond symptomatically and histologically to aggressive gastric acid suppression with a proton pump inhibitor as monotherapy.
3. Swallowed budesonide suspension is effective in treating patients with EE who do not have evidence of GERD.

Participants were randomized based on results of a 24 hour pH study, which determined the average percent time the distal esophagus was exposed to a pH of less than than 4. Subjects with a positive pH result were randomized to esomeprazole or randomized to budesonide, if there was a negative pH result. Studies were interpreted by a single gastroenterologist experienced in reading esophageal pH studies. The percent time the pH monitor detected a pH less than 4 was recorded and an esophageal pH of less than 4 for 4% or greater of the study time was considered abnormal. Note: pH is a measure of acidity or alkalinity (lower numbers are more acid, higher numbers are more alkaline).

Those subjects with GERD (positive pH result) received gastric acid-suppressing medication (esomeprazole 40 mg, twice daily) for 6 weeks. Subjects who did not have GERD (negative pH result) were treated with a corticosteroid designed to coat the esophagus (budesonide suspension 1 mg twice daily) for six weeks. Response to treatment was assessed by esophageal histology and symptoms.

Eligibility criteria: Inclusion Criteria:

1. Patients ages 18-80.
2. Patients who carry the diagnosis of Eosinophilic Esophagitis (EE) based on esophageal biopsies obtained within 18 months prior to enrollment with greater than 15 eosinophils (eos) per high power field (hpf) (400 X magnification).
3. Patients who have moderate, severe, or very severe problems swallowing.

Exclusion Criteria:

1. Patients who are currently being treated for EE.
2. Patients who have used topical or systemic corticosteroid therapy for any reason over the past 4 weeks.
3. Patients who have been treated with acid-suppressing medications (Proton Pump Inhibitor or H2 receptor antagonists) within 4 weeks prior to enrollment.
4. Patients with known allergies or hypersensitivity to proton-pump inhibitors or corticosteroids.
5. Patients who have contraindications to the procurement of biopsies including patients how have known bleeding disorders, a history of bleeding diathesis, or who are currently using warfarin or clopidogrel.
6. Patients who have a contraindication to the performance of an esophagogastroduodenoscopy (EGD) including previous cardiopulmonary arrest during an endoscopic procedure.
7. Patients who have contraindications to the performance of ambulatory impedance 24-hour pH testing including patients with oropharyngeal abnormalities that would prohibit the safe passage of the transnasal catheter and patients who are currently using warfarin, have a history of bleeding disorders or bleeding diatheses.
8. Patients who are pregnant.

Primary outcomes:
measure: Histological Response to Treatment
timeFrame: Baseline, 6 months
measure: Symptomatic Response to Treatment
timeFrame: Baseline, 6 months
Secondary outcomes:
measure: Change in Dysphagia Symptoms in Subjects With Histological Response to Treatment
timeFrame: Baseline, 6 months
measure: Change in Dysphagia Symptoms in Subjects With Non-significant Histological Response to Treatment
timeFrame: Baseline, 6 months
measure: Participants With Presence of Esophageal Rings/Furrows at Six Month Endoscopy
timeFrame: Baseline, 6 months
measure: Participants With Presence of Erosive Esophagitis at Six Month Endoscopy
timeFrame: Baseline, 6 months
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Amy Foxx-Orenstein, D.O.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Francis DL, Foxx-Orenstein A, Arora AS, Smyrk TC, Jensen K, Nord SL, Alexander JA, Romero Y, Katzka DA. Results of ambulatory pH monitoring do not reliably predict response to therapy in patients with eosinophilic oesophagitis. Aliment Pharmacol Ther. 2012 Jan;35(2):300-7. doi: 10.1111/j.1365-2036.2011.04922.x. Epub 2011 Nov 24.