Barrett's EsophagusPhase 3NCT01566474
Melatonin Associated to Acid Inhibition for Chemoprevention in Barret Esophagus: a Pilot Study
A Phase 3 study testing Omeprazole and Melatonin in people with Barrett's Esophagus, run by Aragon Institute of Health Sciences at 1 site in Spain.
Trial summary
The study consists on determining whether melatonin decreases oxidative stress in Barrett's esophageal mucosa after 6 months of treatment. In order to achieve the clinical trial, the patients will be randomized to two possible arms: omeprazole alone or omeprazole plus melatonin. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Barrett's Esophagus
- What is being tested?
- Omeprazole and Melatonin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteSpain
- Study dates
- Apr 2012to Jun 2017
- Phase
- Phase 3
- 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
- Patients (males and females) with Barrett's esophagus (>18 years and <80) without macroscopic esophagitis at endoscopy and a length of the metaplasic mucosa of 2 cm or longer, who agree to participate in the study.
Who cannot join
- Presence of carcinoma or high grade dysplasia at basal endoscopy.
- Previous gastric or esophageal surgery.
- Patients on NSAID or aspirin treatment. A maximum of 5 days per month is allowed. Paracetamol will be used as the standard analgesic treatment.
- Neoplastic malignancies.
- Hematological serious diseases. Coagulation disorders and anemia with Hb < 9.5 gr/dL.
- Serious/moderate cardiac, liver or renal diseases.
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- Need of corticosteroid therapy. A minimum of 5 days per month is allowed, as well as topical or inhaled treatment.
- Patients on misoprostol or anticoagulants.
- Patients with inflammatory bowel disease.
- Allergy to investigational drugs.
Trial locations and contacts
1 site in 1 country.
About this study
The study consists on determining whether melatonin decreases oxidative stress in Barrett's esophageal mucosa after 6 months of treatment. In order to achieve the clinical trial, the patients will be randomized to two possible arms: omeprazole alone or omeprazole plus melatonin. The patients will be followed around four visits during six months.
GERD is one of the most prevalent pathologies in the digestive tract. Barrett's esophagus, a complication of chronic GERD, has attracted the attention of researchers due to its condition of pre-neoplastic lesion. At present, treatment of Barrett's patients is limited to acid inhibition with PPIs. Although there are several studies which indicate that treatment with PPIs could decrease the incidence of high grade dysplasia and EAC, treatment with PPIs does not eliminate the risk of EAC in these patients. Therefore, it is necessary to find chemo-preventive agents that stop neoplastic progression of Barrett's esophagus. Among them, antioxidants have become the most promising agent. This pilot study will determine the efficacy of melatonin in the chemoprevention of EAC.
Read more
So, the main objective of this study is to determine whether melatonin decreases oxidative stress in Barrett's esophageal mucosa after 6 months of treatment.
To evaluate whether melatonin modifies other mechanisms associated to neoplastic progression in BE patients: proliferation and apoptotic index and molecular markers of progression: 17pLOH, 9pLOH, p16 methylation and DNA ploidy (tetraploidy and/or aneuploidy).
Read the detailed description
Barrett's esophagus (BE) is a chronic disease secondary to the presence of stomach acid into the esophagus. This atypical situation produces an inflammation and ulceration of the distal esophagus mucosa. It is the main factor predisposing to the development of esophageal adenocarcinoma, which has a very poor prognosis. At present, therapy of Barrett's esophagus is based on acid secretion inhibition with proton pump inhibitors, which is a very effective therapy to reduce gastroesophageal reflux. However, this therapy does not completely eliminate this risk. Therefore, the better way to follow this disorder is to perform periodic upper gastrointestinal endoscopy and biopsies. Therefore, it is necessary to find new chemo-preventive agents that avoid more efficiently the neoplastic progression of BE. New advances in knowledge about BE suggest that antioxidants could be used to reduce the disorder development. These drugs are being used for long time ago in different pathologies in a lot of countries. One of these drugs is melatonin, which combines several characteristics that suggest it could be the most suitable antioxidant. It has no adverse effects reported.
Patients that meet the following characteristics will be included in this clinical study: Patients (males and females) with Barrett's esophagus (>18 years and <80) without macroscopic esophagitis at endoscopy and a length of the metaplasic mucosa of 2 cm or longer. By the same way, patients will be excluded of the study if present carcinoma or high grade dysplasia at basal endoscopy, previous gastric or esophageal surgery, patients on NSAID or aspirin treatment, neoplastic malignancies, hematological serious diseases (coagulation disorders and anemia with Hb < 9.5 gr/dL), serious/moderate cardiac, liver or renal diseases, need of corticosteroid therapy (a minimum of 5 days per month is allowed, as well as topical or inhaled treatment), patients on misoprostol or anticoagulants, patients with inflammatory bowel disease and allergy to investigational drugs.
Patients, who agree to participate in the study and meet criteria, will be randomized to one of the two following therapies: omeprazole alone or omeprazole + Circadin (melatonin.).
This intervention hardly produces any adverse effects, the most frequent adverse effects of proton pump inhibitors are headache and stomach ache. For melatonin has not reported any adverse effect.
This study will be done in the Hospital Clinico Lozano Blesa (Zaragoza, Spain), promoted by the Health Science Aragon Institute and its principal investigator is Angel Lanas Arbeloa (Digestive Disease Service). It will start in March-april 2012 and will finish 12 months later approximately. The study sponsor is I+CS (Aragon Institute of Health Sciences) that carries the cost of the trial.
- Conditions
- Barrett's Esophagus
- Being tested
- Omeprazole, Melatonin
- 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
Also called Generic omeprazole
Omeprazole 40 mg/day alone. Patients will take the capsule once in the morning before breakfast. This is the standard therapy for patients suffering from Barrett's esophagus.
MelatoninDrug
Also called Circadin
Omeprazole 40 mg/day + Circadin 6 mg/12 hours. Patients will take the Omeprazole capsule once in the morning before breakfast together with 3 tables of 2 mgs of Circadin (melatonin). In the evening, before dinner, patients will take 3 tablets of 2 mg of Circadin.
| Study group | Role | What they receive |
|---|---|---|
| Melatonin + omeprazole | Experimental | Omeprazole 40 mg/day + Circadin 6 mg/12 hours. Patients will take the Omeprazole capsule once in the morning before breakfast together with 3 tables of 2 mgs of Circadin (melatonin). In the evening, before dinner, patients will take 3 tablets of 2 mg of Circadin. Receives: Drug: Melatonin |
| omeprazole | Active comparator | Omeprazole 40 mg/day alone. Patients will take the capsule once in the morning before breakfast. This is the standard therapy for patients suffering from Barrett's esophagus. Receives: Drug: Omeprazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Oxidative stress
- Peroxynitrite production. This variable will be measured by IHQ with a monoclonal Ab against nitrotyrosine residues in biopsy specimens taken from the metaplastic mucosa of patients with Barrett's esophagus.
- DNA oxidative damage: We will determine levels of 8-hydroxy-2'-deoxyguanosine in biopsy specimens form patients with Barrett's esophagus, as described above. DNA will be extracted with a commercial kit from Qiagen. 8-hydroxy-2'-deoxyguanosina quantification will be carried out by EIA.
Measured: 6 months
Secondary outcomes (2)
Biological markers of diseases progression
- Cell proliferation (Ag ki67-mib1) measured by automatic morphometry NIH-Image 6.1).
- Apoptosis: measured by IHQ with caspase.
- Molecular markers of neoplastic progression.
Measured: 6 months
The presence of DNA anomalies (tetraploidy and aneuploidy.
It will be determined by static cytometry.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2012 (estimated)
- Study startApr 2012
- Primary completionJun 2017
- Study completionJun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aragon Institute of Health Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Angel Lanas Arbeloa, Physician, Principal investigator, Digestive disease service of Hospital Clinico Lozano Blesa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01566474
- Sponsor's protocol ID
- ICS10/0273
- Status last verified
- Sep 2019
- First submitted
- 28 Mar 2012
- Last updated
- 13 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Melatonin Associated to Acid Inhibition for Chemoprevention in Barret Esophagus: a Pilot Study
- ClinicalTrials.gov ID
- NCT01566474
- Acronym / sponsor ID
- ICS10/0273
- Conditions
- Barrett's Esophagus
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Aragon Institute of Health SciencesUniversity, hospital or other
- Study start
- Apr 2012
- Primary completion
- Jun 2017 (actual)
- Study completion
- Jun 2017 (actual)
- First posted
- 29 Mar 2012 (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 study consists on determining whether melatonin decreases oxidative stress in Barrett's esophageal mucosa after 6 months of treatment. In order to achieve the clinical trial, the patients will be randomized to two possible arms: omeprazole alone or omeprazole plus melatonin. The patients will be followed around four visits during six months.
GERD is one of the most prevalent pathologies in the digestive tract. Barrett's esophagus, a complication of chronic GERD, has attracted the attention of researchers due to its condition of pre-neoplastic lesion. At present, treatment of Barrett's patients is limited to acid inhibition with PPIs. Although there are several studies which indicate that treatment with PPIs could decrease the incidence of high grade dysplasia and EAC, treatment with PPIs does not eliminate the risk of EAC in these patients. Therefore, it is necessary to find chemo-preventive agents that stop neoplastic progression of Barrett's esophagus. Among them, antioxidants have become the most promising agent. This pilot study will determine the efficacy of melatonin in the chemoprevention of EAC.
So, the main objective of this study is to determine whether melatonin decreases oxidative stress in Barrett's esophageal mucosa after 6 months of treatment.
To evaluate whether melatonin modifies other mechanisms associated to neoplastic progression in BE patients: proliferation and apoptotic index and molecular markers of progression: 17pLOH, 9pLOH, p16 methylation and DNA ploidy (tetraploidy and/or aneuploidy).
Detailed description
Barrett's esophagus (BE) is a chronic disease secondary to the presence of stomach acid into the esophagus. This atypical situation produces an inflammation and ulceration of the distal esophagus mucosa. It is the main factor predisposing to the development of esophageal adenocarcinoma, which has a very poor prognosis. At present, therapy of Barrett's esophagus is based on acid secretion inhibition with proton pump inhibitors, which is a very effective therapy to reduce gastroesophageal reflux. However, this therapy does not completely eliminate this risk. Therefore, the better way to follow this disorder is to perform periodic upper gastrointestinal endoscopy and biopsies. Therefore, it is necessary to find new chemo-preventive agents that avoid more efficiently the neoplastic progression of BE. New advances in knowledge about BE suggest that antioxidants could be used to reduce the disorder development. These drugs are being used for long time ago in different pathologies in a lot of countries. One of these drugs is melatonin, which combines several characteristics that suggest it could be the most suitable antioxidant. It has no adverse effects reported.
Patients that meet the following characteristics will be included in this clinical study: Patients (males and females) with Barrett's esophagus (>18 years and <80) without macroscopic esophagitis at endoscopy and a length of the metaplasic mucosa of 2 cm or longer. By the same way, patients will be excluded of the study if present carcinoma or high grade dysplasia at basal endoscopy, previous gastric or esophageal surgery, patients on NSAID or aspirin treatment, neoplastic malignancies, hematological serious diseases (coagulation disorders and anemia with Hb < 9.5 gr/dL), serious/moderate cardiac, liver or renal diseases, need of corticosteroid therapy (a minimum of 5 days per month is allowed, as well as topical or inhaled treatment), patients on misoprostol or anticoagulants, patients with inflammatory bowel disease and allergy to investigational drugs.
Patients, who agree to participate in the study and meet criteria, will be randomized to one of the two following therapies: omeprazole alone or omeprazole + Circadin (melatonin.).
This intervention hardly produces any adverse effects, the most frequent adverse effects of proton pump inhibitors are headache and stomach ache. For melatonin has not reported any adverse effect.
This study will be done in the Hospital Clinico Lozano Blesa (Zaragoza, Spain), promoted by the Health Science Aragon Institute and its principal investigator is Angel Lanas Arbeloa (Digestive Disease Service). It will start in March-april 2012 and will finish 12 months later approximately. The study sponsor is I+CS (Aragon Institute of Health Sciences) that carries the cost of the trial.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Melatonin + omeprazole | Experimental | Drug: MelatoninOmeprazole 40 mg/day + Circadin 6 mg/12 hours. Patients will take the Omeprazole capsule once in the morning before breakfast together with 3 tables of 2 mgs of Circadin (melatonin). In the evening, before dinner, patients will take 3 tablets of 2 mg of Circadin. |
| omeprazole | Active comparator | Drug: OmeprazoleOmeprazole 40 mg/day alone. Patients will take the capsule once in the morning before breakfast. This is the standard therapy for patients suffering from Barrett's esophagus. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients (males and females) with Barrett's esophagus (>18 years and <80) without macroscopic esophagitis at endoscopy and a length of the metaplasic mucosa of 2 cm or longer, who agree to participate in the study.
Key exclusion criteria (10 listed)
- Presence of carcinoma or high grade dysplasia at basal endoscopy.
- Previous gastric or esophageal surgery.
- Patients on NSAID or aspirin treatment. A maximum of 5 days per month is allowed. Paracetamol will be used as the standard analgesic treatment.
- Neoplastic malignancies.
- Hematological serious diseases. Coagulation disorders and anemia with Hb < 9.5 gr/dL.
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 |
|---|---|---|
| OmeprazoleAlso: Generic omeprazoleOmeprazole 40 mg/day alone. Patients will take the capsule once in the morning before breakfast. This is the standard therapy for patients suffering from Barrett's esophagus. | Drug | omeprazole |
| MelatoninAlso: CircadinOmeprazole 40 mg/day + Circadin 6 mg/12 hours. Patients will take the Omeprazole capsule once in the morning before breakfast together with 3 tables of 2 mgs of Circadin (melatonin). In the evening, before dinner, patients will take 3 tablets of 2 mg of Circadin. | Drug | Melatonin + omeprazole |
Primary outcome
Oxidative stress
Time frame: 6 months
1. Peroxynitrite production. This variable will be measured by IHQ with a monoclonal Ab against nitrotyrosine residues in biopsy specimens taken from the metaplastic mucosa of patients with Barrett's esophagus. 2. DNA oxidative damage: We will determine levels of 8-hydroxy-2'-deoxyguanosine in biopsy specimens form patients with Barrett's esophagus, as described above. DNA will be extracted with a commercial kit from Qiagen. 8-hydroxy-2'-deoxyguanosina quantification will be carried out by EIA.
2 secondary outcomes
Biological markers of diseases progression
Time frame: 6 months
The presence of DNA anomalies (tetraploidy and aneuploidy.
Time frame: 6 months
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 13 Sep 2019.
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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.
Angel Lanas Arbeloa, Physician principal investigator
Digestive disease service of Hospital Clinico Lozano Blesa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Omeprazole and Melatonin in people with Barrett's Esophagus, run by Aragon Institute of Health Sciences at 1 site in Spain.
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 1 inclusion and 10 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 13 Sep 2019. 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 Spain. 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 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?
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?
Oxidative stress (time frame: 6 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 13 Sep 2019.