Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

The Role Of Gastroesophageal Reflux Disease (GERD) in 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.
ClinicalTrials.gov Identifier: NCT00728481
Recruitment Status : Completed
First Posted : August 5, 2008
Results First Posted : December 6, 2012
Last Update Posted : January 14, 2016
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Amy Foxx-Orenstein, Mayo Clinic

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Eosinophilic Esophagitis
Gastroesophageal Reflux Disease
EE
GERD
Interventions Drug: Esomeprazole
Drug: Budesonide
Enrollment 51
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.
Arm/Group Title Esomeprazole Budesonide
Hide Arm/Group Description Proton pump inhibitor; Nexium 40mg capsule taken twice daily by mouth for 6 weeks for subjects with positive 24 hour pH study 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)
Period Title: Overall Study
Started 19 32
Completed 18 28
Not Completed 1 4
Reason Not Completed
Withdrawal by Subject             0             1
Adverse Event             0             1
Study medication non-compliance             0             2
Incorrectly assigned to opposite arm             1             0
Arm/Group Title Esomeprazole Budesonide Total
Hide Arm/Group Description Proton pump inhibitor; Nexium 40mg capsule taken twice daily by mouth for 6 weeks for subjects with positive 24 hour pH study 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) Total of all reporting groups
Overall Number of Baseline Participants 19 32 51
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 19 participants 32 participants 51 participants
47.5  (14.9) 33.7  (10.4) 39  (13.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 32 participants 51 participants
Female
7
  36.8%
13
  40.6%
20
  39.2%
Male
12
  63.2%
19
  59.4%
31
  60.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 19 participants 32 participants 51 participants
19 32 51
Mean number of eosinophils per high powered field in esophagus   [1] 
Mean (Standard Deviation)
Unit of measure:  Eos/hpf
Number Analyzed 19 participants 32 participants 51 participants
35.6  (24.7) 46.7  (26.5) 41.2  (27.7)
[1]
Measure Description: Mean eosinophilic density per high power field [eos/hpf] (at 400 x magnification) of four esophageal biopsies each taken from the proximal & distal esophagus at some point 18 months or less prior to study enrollment.
Endoscopic evidence of GERD   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 19 participants 32 participants 51 participants
Multiple rings (felinization or corrugations) 14 18 32
Hiatal hernia 15 10 25
Erosive esophagitis 7 2 9
[1]
Measure Description: Participants could have had more than one symptom of GERD, or no symptoms of GERD.
Number of participants with frequent GERD/dysphagia symptoms   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 19 participants 32 participants 51 participants
Frequent symptoms 15 0 15
No or infrequent symptoms 3 17 20
No symptoms 0 15 15
[1]
Measure Description:

The GERD portion of the Mayo Dysphagia Questionnaire-30 day (MDQ-30) was used to evaluate the frequency of GERD symptoms. The Mayo Dysphagia Questionnaire is a validated 28 item instrument; 0 = no dysphagia, higher levels indicate greater dysphagia severity.

Note: 18 of the 19 participants with GERD completed the questionnaire.

1.Primary Outcome
Title Histological Response to Treatment
Hide Description 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.
Time Frame Baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Esomeprazole Budesonide
Hide Arm/Group Description:
Proton pump inhibitor; Nexium 40mg capsule taken twice daily by mouth for 6 weeks for subjects with positive 24 hour pH study
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)
Overall Number of Participants Analyzed 18 28
Measure Type: Number
Unit of Measure: Participants
Subjects with histological response 11 16
Subjects with nonsignificant histological response 7 12
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Esomeprazole, Budesonide
Comments Comparison between arms for a histologic response
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
2.Primary Outcome
Title Symptomatic Response to Treatment
Hide Description

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.

Time Frame Baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Esomeprazole Budesonide
Hide Arm/Group Description:
Proton pump inhibitor; Nexium 40mg capsule taken twice daily by mouth for 6 weeks for subjects with positive 24 hour pH study
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)
Overall Number of Participants Analyzed 18 28
Measure Type: Number
Unit of Measure: Participants
Subjects with response in dysphagia symptoms 11 15
Subjects with no response in dysphagia symptoms 7 13
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Esomeprazole, Budesonide
Comments Comparison between arms for a symptomatic response
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.76
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
3.Secondary Outcome
Title Change in Dysphagia Symptoms in Subjects With Histological Response to Treatment
Hide Description 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.
Time Frame Baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population includes only subjects with a histologic response. Subjects were considered to have a histological response to treatment if both sets of biopsies (from distal & mid-esophagus) had, on average, less than 5 eos/hpf.
Arm/Group Title Esomeprazole Budesonide
Hide Arm/Group Description:
Proton pump inhibitor; Nexium 40mg capsule taken twice daily by mouth for 6 weeks for subjects with positive 24 hour pH study
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)
Overall Number of Participants Analyzed 11 16
Measure Type: Number
Unit of Measure: Participants
Dysphagia symptoms improved 5 11
Dysphagia symptoms did not improve 6 5
4.Secondary Outcome
Title Change in Dysphagia Symptoms in Subjects With Non-significant Histological Response to Treatment
Hide Description 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.
Time Frame Baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population for this item only included subjects with a non-significant histologic response. Subjects were considered to have a histological response to treatment if both sets of 6-month biopsies (from distal & mid-esophagus) had, on average, less than 5 eos/hpf.
Arm/Group Title Esomeprazole Budesonide
Hide Arm/Group Description:
Proton pump inhibitor; Nexium 40mg capsule taken twice daily by mouth for 6 weeks for subjects with positive 24 hour pH study
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)
Overall Number of Participants Analyzed 7 12
Measure Type: Number
Unit of Measure: Participants
Dysphagia symptoms responded to treatment 6 4
Dysphagia symptoms did not respond 1 8
5.Secondary Outcome
Title Participants With Presence of Esophageal Rings/Furrows at Six Month Endoscopy
Hide Description Multiple concentric rings or furrows of the esophagus is an endoscopic finding traditionally ascribed to eosinophilic esophagitis.
Time Frame Baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Esomeprazole Budesonide
Hide Arm/Group Description:
Proton pump inhibitor; Nexium 40mg capsule taken twice daily by mouth for 6 weeks for subjects with positive 24 hour pH study
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)
Overall Number of Participants Analyzed 18 28
Measure Type: Number
Unit of Measure: participants
11 17
6.Secondary Outcome
Title Participants With Presence of Erosive Esophagitis at Six Month Endoscopy
Hide Description [Not Specified]
Time Frame Baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Esomeprazole Budesonide
Hide Arm/Group Description:
Proton pump inhibitor; Nexium 40mg capsule taken twice daily by mouth for 6 weeks for subjects with positive 24 hour pH study
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)
Overall Number of Participants Analyzed 18 28
Measure Type: Number
Unit of Measure: participants
1 8
Time Frame Baseline to 6 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Esomeprazole Budesonide
Hide Arm/Group Description Proton pump inhibitor; Nexium 40mg capsule taken twice daily by mouth for 6 weeks for subjects with positive 24 hour pH study 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)
All-Cause Mortality
Esomeprazole Budesonide
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Esomeprazole Budesonide
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/18 (0.00%)      0/28 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Esomeprazole Budesonide
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/18 (5.56%)      1/28 (3.57%)    
Immune system disorders     
Hives * [1]  1/18 (5.56%)  1 1/28 (3.57%)  1
*
Indicates events were collected by non-systematic assessment
[1]
Subject experienced hives with the initiation of budesonide dosing and withdrew from the study.

The index endoscopy was obtained solely for clinical reasons and could have been done as long as 18 months prior to study enrollment.

A single question on the dysphagia questionnaire was used to assess dysphagia symptom response.

Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dr. Amy Foxx-Orenstein, D.O., Associate Prof. of Medicine, College of Medicine
Organization: Mayo Clinic
Phone: 480-301-8806
Responsible Party: Amy Foxx-Orenstein, Mayo Clinic
ClinicalTrials.gov Identifier: NCT00728481     History of Changes
Other Study ID Numbers: 07-006685
First Submitted: July 15, 2008
First Posted: August 5, 2008
Results First Submitted: October 5, 2012
Results First Posted: December 6, 2012
Last Update Posted: January 14, 2016