SThe Effects of Melatonin on GERD Symptoms

Background: Gastroesophageal reflux disease (GERD) is a chronic, persistent and common medical problem. The standard of care for GERD includes chronic administration of acid-suppressive drugs. However, clinical failure in GERD is increasingly reported.

Aim: To determine the efficacy of treatment with melatonin as compared to standard dose proton pump inhibitor (PPI) as compared to placebo in patients with GERD.

Study objectives: [1] To compare the degree of GERD symptoms improvement and esophageal acid sensitivity before and after treatment. [2] To determine the effect of treatment on the % total, upright and supine time pH <4 using 24-hour esophageal pH monitoring. [3] To determine the effect of treatment on frequency and duration of lower esophageal sphincter relaxation. [4] To compare the quality of life and quality of sleep in GERD patients before and after treatment.

Methods: This is a randomized, double blind, parallel groups study of 150 patients with GERD. Patients with classic heartburn symptoms (heartburn and/or regurgitation) and normal upper endoscopy from the gastroenterology department at Rabin Medical Center will be enrolled into the study. At baseline, all enrolled patients will have 24-hour esophageal pH monitoring and a modified acid perfusion test to assess the extent of distal esophageal acid exposure and esophageal acid sensitivity, respectively. Patients will be evaluated by a demographics questionnaire, the GERD Symptom Questionnaire, the Quality of Sleep questionnaire and the SF-36. Baseline urinary excretion of the main melatonin metabolite, 6-sulfatoxymelatonin (6SMT) will be assessed in all subjects at baseline. Patients will be randomized to either melatonin or standard dose PPI or placebo over a period of 4 weeks. In addition patients will fill a diary on a daily basis that documents severity and frequency of GERD-related symptoms. Symptom score (frequency x severity) will be calculated for previous 7 days at baseline and at the end of treatment in all groups. After 4 weeks of treatment, patients will undergo a second 24-hour esophageal pH monitoring, a modified acid perfusion test and will complete the GERD Symptom Questionnaire, the Quality of Sleep Questionnaire and the SF-36.

Implications: This study will determine if melatonin decreases GERD symptoms, acid esophageal exposure and improves quality of life and sleep in patients with GERD. Furthermore, if there will be a significant clinical response to melatonin it will be possible to add this compound to the treatment armamentum of GERD.