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

NCT01566474 | Completed Phase 3 DMC

• 1 other identifier: ICS10/0273
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Barrett's Esophagus

Outcome Measures

Primary Outcomes (1)

• Oxidative stress

  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.

  6 months

Secondary Outcomes (2)

• Biological markers of diseases progression

  6 months

• The presence of DNA anomalies (tetraploidy and aneuploidy.

  6 months

Study Arms (2)

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.

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.

Drug: Omeprazole

Interventions

Omeprazole DRUG

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.

Also known as: Generic omeprazole

omeprazole

Melatonin DRUG

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.

Also known as: Circadin

Melatonin + omeprazole

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Aragon Institute of Health Sciences: lead

Study Sites (1)

Hospital Clínico Universitario Lozano Blesa

Zaragoza, 50009, Spain

Location

MeSH Terms

Conditions

Barrett Esophagus

Interventions

Omeprazole; Melatonin

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indoles; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Angel Lanas Arbeloa, Physician

  Digestive disease service of Hospital Clinico Lozano Blesa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2012
• First Posted: March 29, 2012
• Study Start: April 1, 2012
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2017
• Last Updated: September 13, 2019

Record last verified: 2019-09

Locations

ES (1)