Eosinophilic EsophagitisPhase 2/3NCT00728481
The Role Of Gastroesophageal Reflux Disease (GERD) in Eosinophilic Esophagitis
A Phase 2/3 study testing Esomeprazole and Budesonide in people with Eosinophilic Esophagitis and Gastroesophageal Reflux Disease, run by Mayo Clinic at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Eosinophilic Esophagitis, Gastroesophageal Reflux Disease, EE
- What is being tested?
- Esomeprazole and Budesonide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 1 siteUnited States
- Study dates
- May 2008to Dec 2010
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients ages 18-80.
- 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).
- Patients who have moderate, severe, or very severe problems swallowing.
Who cannot join
- Patients who are currently being treated for EE.
- Patients who have used topical or systemic corticosteroid therapy for any reason over the past 4 weeks.
- Patients who have been treated with acid-suppressing medications (Proton Pump Inhibitor or H2 receptor antagonists) within 4 weeks prior to enrollment.
- Patients with known allergies or hypersensitivity to proton-pump inhibitors or corticosteroids.
- 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.
- Patients who have a contraindication to the performance of an esophagogastroduodenoscopy (EGD) including previous cardiopulmonary arrest during an endoscopic procedure.
- 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.
- Patients who are pregnant.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
Hypotheses:
- There is a subset of patients with the diagnosis of EE who also have GERD.
- Patients with both EE and GERD will respond symptomatically and histologically to aggressive gastric acid suppression with a proton pump inhibitor as monotherapy.
- 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.
- Conditions
- Eosinophilic Esophagitis, Gastroesophageal Reflux Disease, EE, GERD
- Being tested
- Esomeprazole, Budesonide
- Medical subject headings
- Eosinophilic Esophagitis, Gastroesophageal Reflux
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EsomeprazoleDrug
Also called Nexium
Proton pump inhibitor; Nexium 40mg capsule taken twice daily by mouth for 6 weeks
BudesonideDrug
Also called Pulmicort
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 group | Role | What they receive |
|---|---|---|
| Esomeprazole | Active comparator | Proton pump inhibitor; Nexium 40mg capsule taken twice daily by mouth for 6 weeks for subjects with positive 24 hour pH study (GERD) Receives: Drug: Esomeprazole |
| Budesonide | Active comparator | 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) Receives: Drug: Budesonide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, 6 months
Symptomatic Response to Treatment
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.
Measured: Baseline, 6 months
Secondary outcomes (4)
Change in Dysphagia Symptoms in Subjects With Histological Response to Treatment
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.
Measured: Baseline, 6 months
Change in Dysphagia Symptoms in Subjects With Non-significant Histological Response to Treatment
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.
Measured: Baseline, 6 months
Participants With Presence of Esophageal Rings/Furrows at Six Month Endoscopy
Multiple concentric rings or furrows of the esophagus is an endoscopic finding traditionally ascribed to eosinophilic esophagitis.
Measured: Baseline, 6 months
Participants With Presence of Erosive Esophagitis at Six Month Endoscopy
Measured: Baseline, 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2008 (estimated)
- Study startMay 2008
- Primary completionDec 2010
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Eosinophilic EsophagitisStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Principal investigator, Amy Foxx-Orenstein, Mayo Clinic
- Investigators
- Amy Foxx-Orenstein, D.O., Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00728481
- Sponsor's protocol ID
- 07-006685
- Status last verified
- Jan 2016
- First submitted
- 15 Jul 2008
- Last updated
- 14 Jan 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 22111863
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role Of Gastroesophageal Reflux Disease (GERD) in Eosinophilic Esophagitis
- ClinicalTrials.gov ID
- NCT00728481
- Acronym / sponsor ID
- 07-006685
- Conditions
- Eosinophilic Esophagitis, Gastroesophageal Reflux Disease, EE, GERD
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- May 2008
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 5 Aug 2008 (estimated)
- Results
- Posted 6 Dec 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- There is a subset of patients with the diagnosis of EE who also have GERD.
- Patients with both EE and GERD will respond symptomatically and histologically to aggressive gastric acid suppression with a proton pump inhibitor as monotherapy.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Esomeprazole | Active comparator | Drug: EsomeprazoleProton pump inhibitor; Nexium 40mg capsule taken twice daily by mouth for 6 weeks for subjects with positive 24 hour pH study (GERD) |
| Budesonide | Active comparator | Drug: BudesonideCorticosteroid 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) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients ages 18-80.
- 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).
- Patients who have moderate, severe, or very severe problems swallowing.
Key exclusion criteria (8 listed)
- Patients who are currently being treated for EE.
- Patients who have used topical or systemic corticosteroid therapy for any reason over the past 4 weeks.
- Patients who have been treated with acid-suppressing medications (Proton Pump Inhibitor or H2 receptor antagonists) within 4 weeks prior to enrollment.
- Patients with known allergies or hypersensitivity to proton-pump inhibitors or corticosteroids.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EsomeprazoleAlso: NexiumProton pump inhibitor; Nexium 40mg capsule taken twice daily by mouth for 6 weeks | Drug | Esomeprazole |
| BudesonideAlso: PulmicortCorticosteroid 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) | Drug | Budesonide |
Primary outcome
Histological Response to Treatment
Time frame: 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
Time frame: 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.
4 secondary outcomes
Change in Dysphagia Symptoms in Subjects With Histological Response to Treatment
Time frame: Baseline, 6 months
Change in Dysphagia Symptoms in Subjects With Non-significant Histological Response to Treatment
Time frame: Baseline, 6 months
Participants With Presence of Esophageal Rings/Furrows at Six Month Endoscopy
Time frame: Baseline, 6 months
Participants With Presence of Erosive Esophagitis at Six Month Endoscopy
Time frame: Baseline, 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22111863Francis 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amy Foxx-Orenstein, D.O. principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Esomeprazole and Budesonide in people with Eosinophilic Esophagitis and Gastroesophageal Reflux Disease, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Dec 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Histological Response to Treatment (time frame: Baseline, 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00728481, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2016.