The Role Of Gastroesophageal Reflux Disease (GERD) in Eosinophilic Esophagitis

Status

Completed

Phases

Phase 2Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00728481

Enrollment

Registered

2008-08-05

Start date

2008-05-31

Completion date

2010-12-31

Last updated

2016-01-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

EE, Eosinophilic Esophagitis, Gastroesophageal Reflux Disease, GERD

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.

Interventions

DRUGEsomeprazole

Proton pump inhibitor; Nexium 40mg capsule taken twice daily by mouth for 6 weeks

DRUGBudesonide

Corticosteroid therapy; oral viscous Pulmicort Respules 1 gram taken by mouth orally twice daily (mixed with 1 gram packet of Sucralose \[Splenda-registered trademark\]) for 6 weeks in subjects with negative 24 hour pH studies (without GERD)

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 80 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Histological Response to Treatment	Baseline, 6 months	Subjects with Esophageal eosinophilia experiencing a histological response to treatment. Subjects were considered to have histological response to treatment if both sets of biopsies (from the distal and mid-esophagus) had, on average, less than 5 eosinophils per high power field (eos/hpf) at the 6-month biopsies.
Symptomatic Response to Treatment	Baseline, 6 months	Subjects with Esophageal eosinophilia experiencing a response in their dysphagia symptoms to treatment. Symptomatic improvement in symptoms was defined as a score of at least two levels lower than the baseline dysphagia symptom question on the Mayo Dysphagia Questionnaire-30 days (MDQ-30). Dysphagia symptoms were determined based on the MDQ-30 question: 'How would you rate the severity of your trouble swallowing in the past 30 days' with a 5 point scale ranging from 'does not bother me at all' to 'very severe, markedly affects my lifestyle'. Patients must have marked a score of 3 or higher corresponding to 'Moderate, cannot be ignored, but does not affect my lifestyle' to be included in the study.

Secondary

Measure	Time frame	Description
Change in Dysphagia Symptoms in Subjects With Histological Response to Treatment	Baseline, 6 months	Dysphagia symptoms were determined based on the Mayo Dysphagia Questionnaire-30 days (MDQ-30), using the question: 'How would you rate the severity of your trouble swallowing in the past 30 days' with a 5 point scale ranging from 'does not bother me at all' to 'very severe, markedly affects my lifestyle'. Symptomatic improvement was defined as only an improvement of 2 levels on this question.
Change in Dysphagia Symptoms in Subjects With Non-significant Histological Response to Treatment	Baseline, 6 months	Dysphagia symptoms were determined based on the Mayo Dysphagia Questionnaire-30 days (MDQ-30), using the question: 'How would you rate the severity of your trouble swallowing in the past 30 days' with a 5 point scale ranging from 'does not bother me at all' to 'very severe, markedly affects my lifestyle'. Patients must have marked a score of 3 or higher corresponding to 'Moderate, cannot be ignored, but does not affect my lifestyle' to be included in the study.
Participants With Presence of Esophageal Rings/Furrows at Six Month Endoscopy	Baseline, 6 months	Multiple concentric rings or furrows of the esophagus is an endoscopic finding traditionally ascribed to eosinophilic esophagitis.
Participants With Presence of Erosive Esophagitis at Six Month Endoscopy	Baseline, 6 months	—

Countries

United States

Participant flow

Recruitment details

Subjects with a clinical diagnosis of Eosinophilic Esophagitis (EE) were recruited by mail using a Mayo Clinic proprietary database and also by direct contact in the Mayo Clinic Esophageal Diseases speciality clinic in Rochester, MN. Subjects were enrolled from 3/2009 to 8/2010.

Pre-assignment details

Patients with esophageal eosinophilic infiltration of greater than or equal to 15 eos/hpf as determined by 4 biopsies of the esophagus, then underwent a 24-hour transnasal catheter-based ambulatory pH study to determine amount of distal esophageal acid exposure, and were placed in one of 2 treatment arms based on positive or negative pH results.

Participants by arm

Arm	Count
Esomeprazole Proton pump inhibitor; Nexium 40mg capsule taken twice daily by mouth for 6 weeks for subjects with positive 24 hour pH study	19
Budesonide Corticosteroid therapy; oral viscous Pulmicort Respules 1 gram taken by mouth orally twice daily (mixed with 1 gram packet of Sucralose \[Splenda-registered trademark\]) for 6 weeks in subjects with negative 24 hour pH studies (without GERD)	32
Total	51

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	0	1
Overall Study	Incorrectly assigned to opposite arm	1	0
Overall Study	Study medication non-compliance	0	2
Overall Study	Withdrawal by Subject	0	1

Baseline characteristics

Characteristic	Esomeprazole	Budesonide	Total
Age, Continuous	47.5 years STANDARD_DEVIATION 14.9	33.7 years STANDARD_DEVIATION 10.4	39 years STANDARD_DEVIATION 13.9
Endoscopic evidence of GERD Erosive esophagitis	7 Participants	2 Participants	9 Participants
Endoscopic evidence of GERD Hiatal hernia	15 Participants	10 Participants	25 Participants
Endoscopic evidence of GERD Multiple rings (felinization or corrugations)	14 Participants	18 Participants	32 Participants
Mean number of eosinophils per high powered field in esophagus	35.6 eos/hpf STANDARD_DEVIATION 24.7	46.7 eos/hpf STANDARD_DEVIATION 26.5	41.2 eos/hpf STANDARD_DEVIATION 27.7
Number of participants with frequent GERD/dysphagia symptoms Frequent symptoms	15 participants	0 participants	15 participants
Number of participants with frequent GERD/dysphagia symptoms No or infrequent symptoms	3 participants	17 participants	20 participants
Number of participants with frequent GERD/dysphagia symptoms No symptoms	0 participants	15 participants	15 participants
Region of Enrollment United States	19 participants	32 participants	51 participants
Sex: Female, Male Female	7 Participants	13 Participants	20 Participants
Sex: Female, Male Male	12 Participants	19 Participants	31 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	1 / 18	1 / 28
serious Total, serious adverse events	0 / 18	0 / 28

Outcome results

Primary

Histological Response to Treatment

Subjects with Esophageal eosinophilia experiencing a histological response to treatment. Subjects were considered to have histological response to treatment if both sets of biopsies (from the distal and mid-esophagus) had, on average, less than 5 eosinophils per high power field (eos/hpf) at the 6-month biopsies.