Short Segment Barrett's EsophagusEarly Phase 1NCT01465113
Vitamin D Supplementation on 15-Prostaglandin Dehydrogenase Expression in Barrett's Esophagus
A Early Phase 1 study testing Omeprazole, Vitamin D3 and upper endoscopy in people with Short Segment Barrett's Esophagus and Long Segment Barrett's Esophagus, run by Case Comprehensive Cancer Center at 3 sites in United States.
Trial summary
This study is being conducted to determine if vitamin D supplementation increases the level of a protein that may be involved in decreasing the risk of esophageal cancer in patients with Barrett's esophagus. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Short Segment Barrett's Esophagus, Long Segment Barrett's Esophagus
- What is being tested?
- Omeprazole, Vitamin D3 and upper endoscopy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 3 sitesUnited States
- Study dates
- May 2010to Feb 2016
- Phase
- Early Phase 1
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Known diagnosis of short-segment or long-segment Barrett's esophagus as previously made by upper endoscopy showing salmon-colored distal esophageal mucosa and biopsies revealing intestinal metaplasia with goblet cells. Potential study subjects may be contacted by mailings or phone calls or may be approached in clinic. Additionally, potential study subjects may be approached using a web-based recruitment tool. Informed consent will be obtained by a research coordinator or study investigator.
- Subjects may be taking calcium supplements or have previous history of hypercalcemia
- Subjects may have diabetes mellitus
- Subjects may have a history of prior malignancy except for esophageal adenocarcinoma
- Willing to donate 90 mL of blood and endoscopic mucosal biopsies for research
- The following additional inclusion criteria apply for patients in the Vitamin D/metformin sub-arm of the low grade dysplasia/no dysplasia arm:
- At least 2 cm circumferential Barrett's esophagus segment length (C2M2 by Prague C \& M criteria)
- Normal renal function (defined as creatinine within normal institutional limits)
Who cannot join
- Pregnancy
- Known chronic liver disease (Child's B cirrhosis)
- Known chronic kidney disease (creatinine ≥ 3.0)
- Esophageal adenocarcinoma
- Allergic reaction to omeprazole
- Allergic reaction to vitamin D
Show all 19Show fewer
- Unable or unwilling to provide informed consent
- Known hypercalcemia
- Previous ablative therapy for Barrett's esophagus
- Patients on a stable (>/=4 week duration) dose of >2000 IU/day (or equivalent) of vitamin D supplementation
- The following additional exclusion criteria apply for patients in the Vitamin D/metformin sub-arm of the no dysplasia/low grade dysplasia arm:
- Allergic reaction to metformin
- History of diabetes mellitus
- History of lactic acidosis
- History of B12 deficiency
- Participants may not be using metformin, cimetidine (Tagamet) furosemide (Lasix), nifedipine (Cardizem), or any other drug contraindicated for use with metformin.
- Treatment with other oral hypoglycemic agents
- Participants planning to undergo elective radiologic studies involving intravascular administration of iodinated contrast materials.
- Known chronic kidney disease with creatinine greater than normal institutional limits
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University Hospitals Ahuja Medical Center
Beachwood, Ohio, 44122
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, 44195
About this study
Official title: Effect of Vitamin D Supplementation on 15-Prostaglandin Dehydrogenase Expression in Barrett's Esophagus
This study is being conducted to determine if vitamin D supplementation increases the level of a protein that may be involved in decreasing the risk of esophageal cancer in patients with Barrett's esophagus. Subjects with Barrett's esophagus will take vitamin D supplementation for 2-12 weeks depending on the severity of their condition, and receive an upper endoscopy procedure before and after vitamin D supplementation trial.
Read the detailed description
28-day run-in phase during which subjects are treated with a proton pump inhibitor (omeprazole 20 mg po q day or an equivalent dose of another proton pump inhibitor). The purpose of the run-in phase is to minimize esophagitis, which can cause histologic changes that can be confused with dysplasia. After the run-in phase, subjects will undergo an upper endoscopy for Barrett's surveillance or Barrett's mapping as part of routine clinical care. At the time of endoscopy, research biopsies will be obtained for the study. Subjects eligible and continuing in the study will take vitamin D3 (Cholecalciferol) 50,000 IU capsules once weekly with or without daily metformin for a total of two or twelve weeks depending on the severity of Barrett's esophagus. After completion of vitamin D3 subjects will return for an EGD (endoscopy) and biopsies for the research study.
- Being tested
- Omeprazole, Vitamin D3, upper endoscopy, Metformin
- Keywords
- Barrett's Esophagus, Vitamin D3, cholecalciferol, 15-Prostaglandin Dehydrogenase Expression, metformin
- Medical subject headings
- Barrett Esophagus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OmeprazoleDrug
28-day run-in phase during which subjects are treated with a proton pump inhibitor (omeprazole 20 mg po q day or an equivalent dose of another proton pump inhibitor).
Vitamin D3Drug
Also called Cholecalciferol
These patients (indefinite for dysplasia, LGD, or no dysplasia) will take vitamin D3 50,000 IU once a week for 12 weeks following the upper endoscopy.
Vitamin D3Drug
Also called Cholecalciferol
Due to the risk of progression, subjects with Barrett's esophagus with high grade dysplasia will take vitamin D3 50,000 IU once a week for 2 weeks.
upper endoscopyProcedure or surgery
After the run-in phase subjects will undergo an upper endoscopy for Barrett's surveillance or Barrett's mapping as part of routine clinical care. At the time of endoscopy, in addition to large cup forceps biopsies obtained for surveillance or mapping as part of standard care, research biopsies will be obtained for the study. Following vitamin D3 supplementation, all subjects will undergo a repeat upper endoscopy for additional large cup forceps biopsies for measurement of post-treatment mucosal levels.
MetforminDrug
500mg for the first week, 1000mg during the second week, 1500mg during the third week, maximum dose of 2000mg in the fourth week
| Study group | Role | What they receive |
|---|---|---|
| Indefinite, LGD or no dysplasia arm | Experimental | Barrett's esophagus patients who have no dysplasia or low grade dysplasia Receives: Drug: Omeprazole; Drug: Vitamin D3; Procedure: upper endoscopy |
| high grade dysplasia | Experimental | Barrett's esophagus with high grade dysplasia Receives: Drug: Omeprazole; Drug: Vitamin D3; Procedure: upper endoscopy |
| Indefinite, LGD or no dysplasia arm:Vitamin D/Metformin Subarm | Experimental | Barrett's esophagus patients who have no dysplasia or low grade dysplasia Receives: Drug: Omeprazole; Drug: Vitamin D3; Procedure: upper endoscopy; Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Arm 1(no or low grade dysplasia): 15-Prostaglandin dehydrogenase expression
To determine whether vitamin D supplementation induces 15-Prostaglandin dehydrogenase expression as measured by RT-PCR in Barrett's esophagus
Measured: after 12 weeks of vitamin D supplement
Arm 2 (high grade dysplasia): 15-Prostaglandin dehydrogenase expression
To determine whether vitamin D supplementation induces 15-Prostaglandin dehydrogenase expression as measured by RT-PCR in Barrett's esophagus
Measured: after 2 weeks of vitamin D supplement
Secondary outcomes (6)
decreased prostaglandin E2 expression in Barrett's esophagus
To determine whether vitamin D supplementation leads to decreased prostaglandin E2 expression in Barrett's esophagus
Measured: after 2 or 12 weeks of vitamin D supplement
effects on cyclooxygenase-2 expression
To determine whether vitamin D supplementation affects cyclooxygenase-2 expression in Barrett's esophagus
Measured: after 2 or 12 weeks after vitamin D supplement
15-Prostaglandin dehydrogenase expression differences between RT-PCR and immunohistochemistry
To determine whether 15-Prostaglandin dehydrogenase expression in Barrett's esophagus differs between RT-PCR and immunohistochemistry
Measured: after 2 or 12 weeks after vitamin D supplement
effects on levels of Ki-67
To determine whether vitamin D supplementation affects levels of Ki-67, a marker for proliferation, in Barrett's esophagus
Measured: after 2 or 12 weeks after vitamin D supplement
effects on levels of caspase
To determine whether vitamin D supplementation affects levels of caspase, a marker for apoptosis, in Barrett's esophagus
Measured: after 2 or 12 weeks of vitamin D supplement
effects on insulin resistance
To determine whether vitamin D supplementation affects insulin resistance in Barrett's esophagus
Measured: after 2 or 12 weeks of vitamin D supplement
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2011 (estimated)
- Study startMay 2010
- Primary completionFeb 2016
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Short Segment Barrett's EsophagusStudies of the same condition, open and under way.
- More trials run by Case Comprehensive Cancer CenterThe 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
- Early Phase 1
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Linda Cummings, MD, Principal investigator, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01465113
- Sponsor's protocol ID
- CASE12209
- Status last verified
- Mar 2016
- First submitted
- 1 Nov 2011
- Last updated
- 10 Mar 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Vitamin D Supplementation on 15-Prostaglandin Dehydrogenase Expression in Barrett's Esophagus
- ClinicalTrials.gov ID
- NCT01465113
- Acronym / sponsor ID
- CASE12209
- Keywords
- Barrett's Esophagus, Vitamin D3, cholecalciferol, 15-Prostaglandin Dehydrogenase Expression, metformin
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- May 2010
- Primary completion
- Feb 2016 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 4 Nov 2011 (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.
This study is being conducted to determine if vitamin D supplementation increases the level of a protein that may be involved in decreasing the risk of esophageal cancer in patients with Barrett's esophagus. Subjects with Barrett's esophagus will take vitamin D supplementation for 2-12 weeks depending on the severity of their condition, and receive an upper endoscopy procedure before and after vitamin D supplementation trial.
Detailed description
28-day run-in phase during which subjects are treated with a proton pump inhibitor (omeprazole 20 mg po q day or an equivalent dose of another proton pump inhibitor). The purpose of the run-in phase is to minimize esophagitis, which can cause histologic changes that can be confused with dysplasia. After the run-in phase, subjects will undergo an upper endoscopy for Barrett's surveillance or Barrett's mapping as part of routine clinical care. At the time of endoscopy, research biopsies will be obtained for the study. Subjects eligible and continuing in the study will take vitamin D3 (Cholecalciferol) 50,000 IU capsules once weekly with or without daily metformin for a total of two or twelve weeks depending on the severity of Barrett's esophagus. After completion of vitamin D3 subjects will return for an EGD (endoscopy) and biopsies for the research study.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Indefinite, LGD or no dysplasia arm | Experimental | Drug: Omeprazole, Drug: Vitamin D3, Procedure: upper endoscopyBarrett's esophagus patients who have no dysplasia or low grade dysplasia |
| high grade dysplasia | Experimental | Drug: Omeprazole, Drug: Vitamin D3, Procedure: upper endoscopyBarrett's esophagus with high grade dysplasia |
| Indefinite, LGD or no dysplasia arm:Vitamin D/Metformin Subarm | Experimental | Drug: Omeprazole, Drug: Vitamin D3, Procedure: upper endoscopy, Drug: MetforminBarrett's esophagus patients who have no dysplasia or low grade dysplasia |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Known diagnosis of short-segment or long-segment Barrett's esophagus as previously made by upper endoscopy showing salmon-colored distal esophageal mucosa and biopsies revealing intestinal metaplasia with goblet cells. Potential study subjects may be contacted by mailings or phone calls or may be approached in clinic. Additionally, potential study subjects may be approached using a web-based recruitment tool. Informed consent will be obtained by a research coordinator or study investigator.
- Subjects may be taking calcium supplements or have previous history of hypercalcemia
- Subjects may have diabetes mellitus
- Subjects may have a history of prior malignancy except for esophageal adenocarcinoma
- Willing to donate 90 mL of blood and endoscopic mucosal biopsies for research
Key exclusion criteria (19 listed)
- Pregnancy
- Known chronic liver disease (Child's B cirrhosis)
- Known chronic kidney disease (creatinine ≥ 3.0)
- Esophageal adenocarcinoma
- Allergic reaction to omeprazole
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 |
|---|---|---|
| Omeprazole28-day run-in phase during which subjects are treated with a proton pump inhibitor (omeprazole 20 mg po q day or an equivalent dose of another proton pump inhibitor). | Drug | Indefinite, LGD or no dysplasia arm, Indefinite, LGD or no dysplasia arm:Vitamin D/Metformin Subarm, high grade dysplasia |
| Vitamin D3Also: CholecalciferolThese patients (indefinite for dysplasia, LGD, or no dysplasia) will take vitamin D3 50,000 IU once a week for 12 weeks following the upper endoscopy. | Drug | Indefinite, LGD or no dysplasia arm, Indefinite, LGD or no dysplasia arm:Vitamin D/Metformin Subarm |
| Vitamin D3Also: CholecalciferolDue to the risk of progression, subjects with Barrett's esophagus with high grade dysplasia will take vitamin D3 50,000 IU once a week for 2 weeks. | Drug | high grade dysplasia |
| upper endoscopyAfter the run-in phase subjects will undergo an upper endoscopy for Barrett's surveillance or Barrett's mapping as part of routine clinical care. At the time of endoscopy, in addition to large cup forceps biopsies obtained for surveillance or mapping as part of standard care, research biopsies will be obtained for the study. Following vitamin D3 supplementation, all subjects will undergo a repeat upper endoscopy for additional large cup forceps biopsies for measurement of post-treatment mucosal levels. | Procedure or surgery | Indefinite, LGD or no dysplasia arm, Indefinite, LGD or no dysplasia arm:Vitamin D/Metformin Subarm, high grade dysplasia |
| Metformin500mg for the first week, 1000mg during the second week, 1500mg during the third week, maximum dose of 2000mg in the fourth week | Drug | Indefinite, LGD or no dysplasia arm:Vitamin D/Metformin Subarm |
Primary outcome
Arm 1(no or low grade dysplasia): 15-Prostaglandin dehydrogenase expression
Time frame: after 12 weeks of vitamin D supplement
To determine whether vitamin D supplementation induces 15-Prostaglandin dehydrogenase expression as measured by RT-PCR in Barrett's esophagus
Arm 2 (high grade dysplasia): 15-Prostaglandin dehydrogenase expression
Time frame: after 2 weeks of vitamin D supplement
To determine whether vitamin D supplementation induces 15-Prostaglandin dehydrogenase expression as measured by RT-PCR in Barrett's esophagus
6 secondary outcomes
decreased prostaglandin E2 expression in Barrett's esophagus
Time frame: after 2 or 12 weeks of vitamin D supplement
effects on cyclooxygenase-2 expression
Time frame: after 2 or 12 weeks after vitamin D supplement
15-Prostaglandin dehydrogenase expression differences between RT-PCR and immunohistochemistry
Time frame: after 2 or 12 weeks after vitamin D supplement
effects on levels of Ki-67
Time frame: after 2 or 12 weeks after vitamin D supplement
effects on levels of caspase
Time frame: after 2 or 12 weeks of vitamin D supplement
effects on insulin resistance
Time frame: after 2 or 12 weeks of vitamin D supplement
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 10 Mar 2016.
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.
Linda Cummings, MD principal investigator
Case Comprehensive Cancer Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Omeprazole, Vitamin D3 and upper endoscopy in people with Short Segment Barrett's Esophagus and Long Segment Barrett's Esophagus, run by Case Comprehensive Cancer Center at 3 sites 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 8 inclusion and 19 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 10 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Arm 1(no or low grade dysplasia): 15-Prostaglandin dehydrogenase expression (time frame: after 12 weeks of vitamin D supplement). 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?
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 10 Mar 2016.