Barrett's EsophagusNCT02579460
Reflux-Induced Oxidative Stress in Barrett's Esophagus: Response, Repair, and Epithelial-Mesenchymal-Transition
A study testing Cessation of Acid Suppressing Medications in people with Barrett's Esophagus and Gastroesophageal Reflux Disease, run by Dallas VA Medical Center at 1 site in United States.
Trial summary
The purpose of this study is to elucidate mechanisms whereby oxidative stress induced by acute reflux esophagitis: 1) activates p38 to regulate proteins that control the G1/S cell cycle checkpoint, and 2) activates HIFs (hypoxia inducible factors) to cause autocrine VEGF (vascular endothelial growth factor) signaling… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Barrett's Esophagus, Gastroesophageal Reflux Disease
- What is being tested?
- Cessation of Acid Suppressing Medications
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2015to Nov 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- U.S. Veteran
- Barrett's Esophagus
Who cannot join
- Inability to provide informed consent
- Pregnancy or breastfeeding
- Esophageal varices
- Warfarin use
- Coagulopathy that precludes safe biopsy of the esophagus
- Comorbidity that precludes safe participation in the study
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to elucidate mechanisms whereby oxidative stress induced by acute reflux esophagitis: 1) activates p38 to regulate proteins that control the G1/S cell cycle checkpoint, and 2) activates HIFs (hypoxia inducible factors) to cause autocrine VEGF (vascular endothelial growth factor) signaling that triggers the EMT (epithelial-mesenchymal-transition) program in Barrett's esophagus.
Read the detailed description
Gastroesophageal reflux disease (GERD) and its complication, Barrett's esophagus (BE), are risk factors for esophageal adenocarcinoma. In BE, GERD causes inflammation with oxidative DNA damage and genomic instability that contributes to carcinogenesis. In BE, one response to oxidative stress is p38 pathway activation, which might protect against cancer development by initiating G1 arrest and enabling repair of DNA damage. Inflammation and oxidative stress also might induce epithelial-mesenchymal transition (EMT), the process in which epithelial cells acquire mesenchymal characteristics including the ability to migrate. This study will elucidate mechanisms whereby the oxidative stress of acute reflux esophagitis in BE activates p38 to regulate proteins controlling the G1/S cell cycle checkpoint, and activates HIFs to cause autocrine vascular endothelial growth factor (VEGF) signaling that triggers the EMT program.
- Being tested
- Cessation of Acid Suppressing Medications
- Keywords
- Barrett's esophagus, Gastroesophageal Reflux Disease
- Medical subject headings
- Barrett Esophagus, Gastroesophageal Reflux
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cessation of Acid Suppressing MedicationsOther
Acid suppressing medications are stopped for all participants the day after baseline assessment. Subsequent evaluations are performed while the participant is not on acid-suppressing medications. Endoscopy with biopsies will be performed in all patients on day 0, 7, and 14.
| Study group | Role | What they receive |
|---|---|---|
| Barrett's esophagus patients | Experimental | Patients with Barrett's Esophagus will be enrolled. The intervention is cessation of acid-suppressing medications. Biopsies will be taken during endoscopy at Day 0, 7, and 14. Receives: Other: Cessation of Acid Suppressing Medications |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in esophageal mucosal inflammation using histopathological assessment from baseline to 14 days
Inflammation of the esophageal mucosa will be measured at baseline, 7 days, and at 14 days. Esophageal mucosal inflammation will be measured using esophageal mucosal biopsy specimens, and histopatholgical grading. Mucosal infiltration with inflammatory cells (neutrophils, eosinophils, and lymphocytes) will be measured.
Measured: day 0, day 7, and day 14
Secondary outcomes (9)
change in p38 pathway from baseline to 14 days
p38 and components of the p38 pathway will be measured in the esophageal mucosa at baseline, 7 days, and at 14 days
Measured: day 0, day 7, and day 14
change in phosoho-p38 from baseline to 14 days
phospho-p38 will be measured in the esophageal mucosa at baseline, day 7, and at day 14
Measured: day 0, day 7, and day 14
Show oxidative DNA damage associated with p38 activation
OxiSelect Oxidative DNA Damage ELISA assay of Barrett's mucosa at baseline, day 7, and day 14
Measured: day 0, day 7, and day 14
change in VEGF from baseline to 14 days
VEGF will be measured in the esophageal mucosa at baseline, 7 days, and at day 14
Measured: day 0, day 7, and day 14
change in APE-1 from baseline to 14 days
APE-1 will be measured in the esophageal mucosa at baseline, day 7, and at day 14
Measured: day 0, day 7, and day 14
change in NPM1 from baseline to 14 days
NPM-1 will be measured in the esophageal mucosa at baseline, day 7, and at day 14
Measured: day 0, day 7, and day 14
change in phospho-NPM1 from baseline to 14 days
phospho-NPM1 will be measured in the esophageal mucosa at baseline, day 7, and at day 14
Measured: day 0, day 7, and day 14
change in miRNA expression from baseline to 14 days
miRNAs will be measured in the esophageal mucosa and in exosomes isolated from the blood at baseline, day 7, and day 14
Measured: day 0, day 7, and day 14
change in HIF expression from baseline to 14 days
HIF expression will be measured in the esophageal mucosa at baseline, day 7, and day 14
Measured: day 0, day 7, and day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2015 (estimated)
- Study startNov 2015
- Primary completionNov 2017
- Study completionNov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Barrett's EsophagusStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dallas VA Medical Center
- Sponsor type
- US federal agency
- Responsible party
- Principal investigator, Stuart Spechler, Dallas VA Medical Center
- Investigators
- Stuart J Spechler, MD, Principal investigator, Dallas VA Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02579460
- Sponsor's protocol ID
- 15-022
- Other IDs
- 1R01DK103598-01A1
- Status last verified
- Sep 2023
- First submitted
- 14 Oct 2015
- Last updated
- 11 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
Publications
Zhang Q, Dunbar KB, Odze RD, Agoston AT, Wang X, Su T, Nguyen AD, Zhang X, Spechler SJ, Souza RF. Hypoxia-inducible factor-1alpha mediates reflux-induced epithelial-mesenchymal plasticity in Barrett's oesophagus patients. Gut. 2024 Jul 11;73(8):1269-1279. doi: 10.1136/gutjnl-2023-331467.
PubMed 38641363
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reflux-Induced Oxidative Stress in Barrett's Esophagus: Response, Repair, and Epithelial-Mesenchymal-Transition
- ClinicalTrials.gov ID
- NCT02579460
- Acronym / sponsor ID
- 15-022
- Keywords
- Barrett's esophagus, Gastroesophageal Reflux Disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Dallas VA Medical CenterUS federal agency
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Nov 2015 (actual)
- Primary completion
- Nov 2017 (actual)
- Study completion
- Nov 2017 (actual)
- First posted
- 19 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to elucidate mechanisms whereby oxidative stress induced by acute reflux esophagitis: 1) activates p38 to regulate proteins that control the G1/S cell cycle checkpoint, and 2) activates HIFs (hypoxia inducible factors) to cause autocrine VEGF (vascular endothelial growth factor) signaling that triggers the EMT (epithelial-mesenchymal-transition) program in Barrett's esophagus.
Detailed description
Gastroesophageal reflux disease (GERD) and its complication, Barrett's esophagus (BE), are risk factors for esophageal adenocarcinoma. In BE, GERD causes inflammation with oxidative DNA damage and genomic instability that contributes to carcinogenesis. In BE, one response to oxidative stress is p38 pathway activation, which might protect against cancer development by initiating G1 arrest and enabling repair of DNA damage. Inflammation and oxidative stress also might induce epithelial-mesenchymal transition (EMT), the process in which epithelial cells acquire mesenchymal characteristics including the ability to migrate. This study will elucidate mechanisms whereby the oxidative stress of acute reflux esophagitis in BE activates p38 to regulate proteins controlling the G1/S cell cycle checkpoint, and activates HIFs to cause autocrine vascular endothelial growth factor (VEGF) signaling that triggers the EMT program.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Barrett's esophagus patients | Experimental | Other: Cessation of Acid Suppressing MedicationsPatients with Barrett's Esophagus will be enrolled. The intervention is cessation of acid-suppressing medications. Biopsies will be taken during endoscopy at Day 0, 7, and 14. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- U.S. Veteran
- Barrett's Esophagus
Key exclusion criteria (6 listed)
- Inability to provide informed consent
- Pregnancy or breastfeeding
- Esophageal varices
- Warfarin use
- Coagulopathy that precludes safe biopsy of the esophagus
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 |
|---|---|---|
| Cessation of Acid Suppressing MedicationsAcid suppressing medications are stopped for all participants the day after baseline assessment. Subsequent evaluations are performed while the participant is not on acid-suppressing medications. Endoscopy with biopsies will be performed in all patients on day 0, 7, and 14. | Other | Barrett's esophagus patients |
Primary outcome
Change in esophageal mucosal inflammation using histopathological assessment from baseline to 14 days
Time frame: day 0, day 7, and day 14
Inflammation of the esophageal mucosa will be measured at baseline, 7 days, and at 14 days. Esophageal mucosal inflammation will be measured using esophageal mucosal biopsy specimens, and histopatholgical grading. Mucosal infiltration with inflammatory cells (neutrophils, eosinophils, and lymphocytes) will be measured.
9 secondary outcomes
change in p38 pathway from baseline to 14 days
Time frame: day 0, day 7, and day 14
change in phosoho-p38 from baseline to 14 days
Time frame: day 0, day 7, and day 14
Show oxidative DNA damage associated with p38 activation
Time frame: day 0, day 7, and day 14
change in VEGF from baseline to 14 days
Time frame: day 0, day 7, and day 14
change in APE-1 from baseline to 14 days
Time frame: day 0, day 7, and day 14
change in NPM1 from baseline to 14 days
Time frame: day 0, day 7, and day 14
change in phospho-NPM1 from baseline to 14 days
Time frame: day 0, day 7, and day 14
change in miRNA expression from baseline to 14 days
Time frame: day 0, day 7, and day 14
change in HIF expression from baseline to 14 days
Time frame: day 0, day 7, and day 14
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2023.
- Derived from this study: PubMed 38641363Zhang Q, Dunbar KB, Odze RD, Agoston AT, Wang X, Su T, Nguyen AD, Zhang X, Spechler SJ, Souza RF. Hypoxia-inducible factor-1alpha mediates reflux-induced epithelial-mesenchymal plasticity in Barrett's oesophagus patients. Gut. 2024 Jul 11;73(8):1269-1279. doi: 10.1136/gutjnl-2023-331467.
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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.
Stuart J Spechler, MD principal investigator
Dallas VA Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cessation of Acid Suppressing Medications in people with Barrett's Esophagus and Gastroesophageal Reflux Disease, run by Dallas VA Medical Center 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 11 Sep 2023. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change in esophageal mucosal inflammation using histopathological assessment from baseline to 14 days (time frame: day 0, day 7, and day 14). 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 NCT02579460, 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 11 Sep 2023.