Melatonin Associated to Acid Inhibition for Chemoprevention in Barret Esophagus: a Pilot Study

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by Aragon Institute of Health Sciences
Sponsor:
Information provided by (Responsible Party):
Aragon Institute of Health Sciences
ClinicalTrials.gov Identifier:
NCT01566474
First received: March 28, 2012
Last updated: January 23, 2013
Last verified: January 2013
  Purpose

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).


Condition Intervention Phase
Barrett's Esophagus
Drug: Omeprazole
Drug: Melatonin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Melatonin Associated to Acid Inhibition for Chemoprevention in Barret Esophagus: a Pilot Study

Resource links provided by NLM:


Further study details as provided by Aragon Institute of Health Sciences:

Primary Outcome Measures:
  • Oxidative stress [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Biological markers of diseases progression [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    1. Cell proliferation (Ag ki67-mib1) measured by automatic morphometry NIH-Image 6.1).
    2. Apoptosis: measured by IHQ with caspase.
    3. Molecular markers of neoplastic progression.

  • The presence of DNA anomalies (tetraploidy and aneuploidy. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    It will be determined by static cytometry.


Estimated Enrollment: 80
Study Start Date: April 2012
Estimated Study Completion Date: April 2013
Estimated Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Melatonin + omeprazole
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.
Drug: Melatonin
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.
Other Name: Circadin
Active Comparator: 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.
Drug: 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.
Other Name: Generic omeprazole

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01566474

Locations
Spain
Hospital Clínico Universitario Lozano Blesa Recruiting
Zaragoza, Spain, 50009
Contact: Angel Lanas Arbeloa, Physician    +34 976 765786    alanas@unizar.es   
Principal Investigator: Angel Lanas Arbeloa, Physician         
Sponsors and Collaborators
Aragon Institute of Health Sciences
Investigators
Principal Investigator: Angel Lanas Arbeloa, Physician Digestive disease service of Hospital Clinico Lozano Blesa
  More Information

No publications provided

Responsible Party: Aragon Institute of Health Sciences
ClinicalTrials.gov Identifier: NCT01566474     History of Changes
Other Study ID Numbers: ICS10/0273
Study First Received: March 28, 2012
Last Updated: January 23, 2013
Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios

Additional relevant MeSH terms:
Barrett Esophagus
Digestive System Abnormalities
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Melatonin
Omeprazole
Anti-Ulcer Agents
Antioxidants
Central Nervous System Agents
Central Nervous System Depressants
Enzyme Inhibitors
Gastrointestinal Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Proton Pump Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014