Melatonin Associated to Acid Inhibition for Chemoprevention in Barret Esophagus: a Pilot Study
Condition: Barrett's Esophagus
MeSH terms: Barrett Esophagus
Study type: Interventional
Phase: Phase 3

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. 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.
    

Intervention name(s): Omeprazole; Melatonin
Intervention type(s): Drug; Drug
Intervention description(s): 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.; 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 intervention name(s): Generic omeprazole; Circadin
Intervention MeSH terms: Melatonin; Omeprazole
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Prevention