Esophageal StricturePhase 2NCT02069847
Prospective Evaluation of Budesonide for Prevention of Esophageal Strictures After Endotherapy
A Phase 2 study testing Budesonide in people with Esophageal Stricture, run by Mayo Clinic at 1 site in United States.
Trial summary
Surgery has been historically the mainstay treatment for advanced pre-malignant lesions and early esophageal cancers. However, esophagectomy is associated with significant morbidity and mortality. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Esophageal Stricture
- What is being tested?
- Budesonide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2014to 11 Jan 2019
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 years or older
- Diagnosis of esophageal lesion treated with ESD or EMR which involves ≥ 50% of the esophageal circumference.
Who cannot join
- Locally advanced disease
- Prior esophageal surgery
- Participation in another research protocol that could interfere or influence the outcome measures of the present study.
- The subject or legal representative is unable/unwilling to give informed consent. (study group)
- Medications or conditions for which there is a contraindication to use of budesonide (see pharmacology section below)
- Concomitant use of systemic steroids or other immune suppressive medication for a different condition 9. Pregnant women
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Prospective Evaluation of the Clinical Utility of Budesonide for the Prevention of Esophageal Strictures After Endotherapy
Surgery has been historically the mainstay treatment for advanced pre-malignant lesions and early esophageal cancers. However, esophagectomy is associated with significant morbidity and mortality. With the advance of therapeutic endoscopy, there has been a growing interest and application of endoscopic resection and mucosal ablative techniques for the treatment of these diseases. Esophageal stricture (ES) formation has become an increasingly recognized complication of extensive endoscopic mucosal ablation and/or resection. The resultant symptomatic stricture development can significantly impair a patient's quality of life. Endoscopic therapy of esophageal strictures with balloon dilation and/or local steroid injection is invasive, costly, and associated with the potential risk of perforation. Recently, oral corticosteroids have been introduced for the prevention of esophageal stricture after endoscopic submucosal dissection.
Budesonide is a synthetic steroid with topical anti-inflammatory properties and high first-pass metabolism; thus, potentially less systemic absorption and side effects.
Hypothesis: Oral budesonide prevents esophageal stricture formation in patients who underwent radical endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) for advanced premalignant esophageal lesions or superficial esophageal cancers.
Read the detailed description
Esophageal stricture (ES) formation is a widely recognized adverse event of radical EMR and ESD. Indeed, ES is the most common complication of radiofrequency ablation (RFA) for Barrett's esophagus (BE), with a reported incidence ranging from 5% to 12%. A single-center retrospective study reported ES formation in 67% of 73 patients with EMR of at least 50% of their esophageal circumference. Similarly, the incidence of ES development after ESD is between 70-90% when the mucosal defect involves more than three-quarters of the esophageal circumference. In aggregate, the extent of the esophageal mucosal defect following endotherapy appears to be the most consistent predictor of ES formation. Prevention of ES development following endotherapy can significantly improve a patient's quality of life and possibly reduce the potential risks and costs associated with treatment of ES with repeated endoscopic balloon dilations (EBD). Glucocorticoids have been evaluated as a potential preventive therapy for ES based on their anti-inflammatory properties and inhibitory effects on collagen deposition. Oral prednisolone has been shown to be effective as a preventive strategy for ES formation. However, prolonged use of systemic oral steroids can be associated with multiple adverse effects.
Budesonide is a synthetic steroid with topical anti-inflammatory properties and high first-pass metabolism; thus, potentially less systemic absorption and side effects. Most recently Mayo Clinic Rochester developed a new budesonide capsule formulation. Alike viscous budesonide the budesonide capsule can be opened and the powder can be mixed with honey or pancake syrup. A similar formulation is currently used in pilot studies for treatment of eosinophilic esophagitis. The advantage of budesonide capsule is the improve taste in comparison to viscous budesonide originating from budesonide respules which is unpalatable.
Study aims:
- The aim of this study is to prospectively record our experience with budesonide for the prevention of esophageal stricture formation after endotherapy (mucosal resection, submucosal dissection) as part of routine medical care.
- The data will be compared with outcomes with well-annotated historical controls that underwent similar procedure with similar follow up but without budesonide exposure.
- If sufficient efficacy is seen, these data will be used to plan a prospective controlled clinical trial. All patients in the study group will receive standard medical care and no experimental interventions will be performed.
- Conditions
- Esophageal Stricture
- Being tested
- Budesonide
- Keywords
- Esophageal stricture formation, Endoscopic mucosal resection, Endoscopic submucosal dissection, Budesonide, Radical endoscopic mucosal resection, EMR, ESD
- Medical subject headings
- Esophageal Stenosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BudesonideDrug
Also called Budesonide, Entocort, Uceris
Participants will be instructed to swallow budesonide 3mg twice daily for eight consecutive weeks following endotherapy with EMR or ESD. Budesonide will be provided in a capsule containing 3mg budesonide only by Mayo Clinic Pharmacy with full 8 weeks supply.
The patient will require opening the capsule and mixing the budesonide powder in 10ml (2 teaspoons) honey, or pancake syrup.
Patients will be instructed not to ingest any solid or liquids for 30 minutes before and after taking the budesonide. For purposes of this study, budesonide is used off-label but according to the same dose and efficacy as has been demonstrated in other esophageal inflammatory conditions. Patients will receive a handout with exact instructions how and when to take Budesonide.
| Study group | Role | What they receive |
|---|---|---|
| Esophageal stricture, Budesonide | Experimental | Budesonide 1mg twice a day for a total of 8 weeks following endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR) Receives: Drug: Budesonide |
| Control group | No intervention | Retrospective collect data for subjects who undergo endoscopic submucosal dissection or endoscopic mucosal resection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dysplasia in Barrett Esophagus (BE)
Number of subjects with Non-dysplastic, low grade dysplasia, high grade dysplasia and T1a early esophageal adenocarcinoma. As measured by using the BE dysplasia grading system of Non-dysplastic (no cancerous tissue present), low-grade dysplasia (minor cell changes found), high-grade dysplasia (extensive cell changes found, but not yet cancer), and noninvasive cancer (T1a early esophageal adenocarcinoma)
Measured: 3 months
Secondary outcomes (1)
Rate of Esophageal Stricture
Number of subjects with 50-74%, 75-99% and 100% esophageal stricture. Defined as the percentage of esophageal lumen narrowing requiring dilation prior to passage of the endoscope and/or presence of new dysphagia.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2014 (estimated)
- Study startFeb 2014
- Primary completion11 Jan 2019
- Study completion11 Jan 2019
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.
- Other trials for Esophageal StrictureStudies 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael Wallace, Mayo Clinic
- Investigators
- Michael Wallace, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02069847
- Sponsor's protocol ID
- 13-009467
- Status last verified
- May 2020
- First submitted
- 20 Feb 2014
- Last updated
- 16 Jun 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Evaluation of the Clinical Utility of Budesonide for the Prevention of Esophageal Strictures After Endotherapy
- ClinicalTrials.gov ID
- NCT02069847
- Acronym / sponsor ID
- 13-009467
- Conditions
- Esophageal Stricture
- Keywords
- Esophageal stricture formation, Endoscopic mucosal resection, Endoscopic submucosal dissection, Budesonide, Radical endoscopic mucosal resection, EMR, ESD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- Feb 2014
- Primary completion
- 11 Jan 2019 (actual)
- Study completion
- 11 Jan 2019 (actual)
- First posted
- 24 Feb 2014 (estimated)
- Results
- Posted 16 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Surgery has been historically the mainstay treatment for advanced pre-malignant lesions and early esophageal cancers. However, esophagectomy is associated with significant morbidity and mortality. With the advance of therapeutic endoscopy, there has been a growing interest and application of endoscopic resection and mucosal ablative techniques for the treatment of these diseases. Esophageal stricture (ES) formation has become an increasingly recognized complication of extensive endoscopic mucosal ablation and/or resection. The resultant symptomatic stricture development can significantly impair a patient's quality of life. Endoscopic therapy of esophageal strictures with balloon dilation and/or local steroid injection is invasive, costly, and associated with the potential risk of perforation. Recently, oral corticosteroids have been introduced for the prevention of esophageal stricture after endoscopic submucosal dissection.
Budesonide is a synthetic steroid with topical anti-inflammatory properties and high first-pass metabolism; thus, potentially less systemic absorption and side effects.
Hypothesis: Oral budesonide prevents esophageal stricture formation in patients who underwent radical endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) for advanced premalignant esophageal lesions or superficial esophageal cancers.
Detailed description
Esophageal stricture (ES) formation is a widely recognized adverse event of radical EMR and ESD. Indeed, ES is the most common complication of radiofrequency ablation (RFA) for Barrett's esophagus (BE), with a reported incidence ranging from 5% to 12%. A single-center retrospective study reported ES formation in 67% of 73 patients with EMR of at least 50% of their esophageal circumference. Similarly, the incidence of ES development after ESD is between 70-90% when the mucosal defect involves more than three-quarters of the esophageal circumference. In aggregate, the extent of the esophageal mucosal defect following endotherapy appears to be the most consistent predictor of ES formation. Prevention of ES development following endotherapy can significantly improve a patient's quality of life and possibly reduce the potential risks and costs associated with treatment of ES with repeated endoscopic balloon dilations (EBD). Glucocorticoids have been evaluated as a potential preventive therapy for ES based on their anti-inflammatory properties and inhibitory effects on collagen deposition. Oral prednisolone has been shown to be effective as a preventive strategy for ES formation. However, prolonged use of systemic oral steroids can be associated with multiple adverse effects.
Budesonide is a synthetic steroid with topical anti-inflammatory properties and high first-pass metabolism; thus, potentially less systemic absorption and side effects. Most recently Mayo Clinic Rochester developed a new budesonide capsule formulation. Alike viscous budesonide the budesonide capsule can be opened and the powder can be mixed with honey or pancake syrup. A similar formulation is currently used in pilot studies for treatment of eosinophilic esophagitis. The advantage of budesonide capsule is the improve taste in comparison to viscous budesonide originating from budesonide respules which is unpalatable.
Study aims:
- The aim of this study is to prospectively record our experience with budesonide for the prevention of esophageal stricture formation after endotherapy (mucosal resection, submucosal dissection) as part of routine medical care.
- The data will be compared with outcomes with well-annotated historical controls that underwent similar procedure with similar follow up but without budesonide exposure.
- If sufficient efficacy is seen, these data will be used to plan a prospective controlled clinical trial. All patients in the study group will receive standard medical care and no experimental interventions will be performed.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Esophageal stricture, Budesonide | Experimental | Drug: BudesonideBudesonide 1mg twice a day for a total of 8 weeks following endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR) |
| Control group | No intervention | –Retrospective collect data for subjects who undergo endoscopic submucosal dissection or endoscopic mucosal resection |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Age 18 years or older
- Diagnosis of esophageal lesion treated with ESD or EMR which involves ≥ 50% of the esophageal circumference.
Key exclusion criteria (6 listed)
- Locally advanced disease
- Prior esophageal surgery
- Participation in another research protocol that could interfere or influence the outcome measures of the present study.
- The subject or legal representative is unable/unwilling to give informed consent. (study group)
- Medications or conditions for which there is a contraindication to use of budesonide (see pharmacology section below)
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 |
|---|---|---|
| BudesonideAlso: Budesonide, Entocort, UcerisParticipants will be instructed to swallow budesonide 3mg twice daily for eight consecutive weeks following endotherapy with EMR or ESD. Budesonide will be provided in a capsule containing 3mg budesonide only by Mayo Clinic Pharmacy with full 8 weeks supply. The patient will require opening the capsule and mixing the budesonide powder in 10ml (2 teaspoons) honey, or pancake syrup. Patients will be instructed not to ingest any solid or liquids for 30 minutes before and after taking the budesonide. For purposes of this study, budesonide is used off-label but according to the same dose and efficacy as has been demonstrated in other esophageal inflammatory conditions. Patients will receive a handout with exact instructions how and when to take Budesonide. | Drug | Esophageal stricture, Budesonide |
Primary outcome
Dysplasia in Barrett Esophagus (BE)
Time frame: 3 months
Number of subjects with Non-dysplastic, low grade dysplasia, high grade dysplasia and T1a early esophageal adenocarcinoma. As measured by using the BE dysplasia grading system of Non-dysplastic (no cancerous tissue present), low-grade dysplasia (minor cell changes found), high-grade dysplasia (extensive cell changes found, but not yet cancer), and noninvasive cancer (T1a early esophageal adenocarcinoma)
1 secondary outcome
Rate of Esophageal Stricture
Time frame: 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
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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.
Michael Wallace, MD 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 study testing Budesonide in people with Esophageal Stricture, 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 2 inclusion and 6 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 16 Jun 2020. 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 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.
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 16 Jun 2020). 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?
Dysplasia in Barrett Esophagus (BE) (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Jun 2020.