Materials and Methods
voice hoarseness, heartburn, GERD, chest pain, throat, cirrhosis, reflux symptoms, renal damage, esophageal sphincter loosening foods, duodenal ulcer, Child-Pugh C, peptic ulcer
ESOPHAGEAL DYSPHAGIA, REFLUX, DISEASE, GERD, CIRRHOSIS, MAY, ACUTE KIDNEY INJURY, DUODENAL ULCER, ADVERSE DRUG REACTIONS, PEPTIC ULCER
This double-blind randomized clinical trial was approved by the ethics committees of nursing, midwifery, and pharmacy schools of Shahid Beheshti University of Medical Sciences (code: IR.SBMU.PHARMACY.REC.1400.168) and registered in the Iranian Registry of Clinical Trials (code: IRCT20121021011192N12). Before initiating the clinical stages, melatonin and placebo were prepared and packaged. Melatonin (3 mg) was prepared as sublingual tablets (Vana DarouGostar Pharmaceutical Company, Iran), and the placebo was prepared at the pharmaceutical laboratory of the Shahid Beheshti University of Medical Sciences, with the same appearance as sublingual melatonin, according to the main drug formulation without melatonin.The clinical stages of this study were initiated on May 1, 2022 and continued until October 1, 2022. The patients were randomly assigned to either the melatonin or placebo group based on the table of random numbers. The patients, physician, and examiner were blinded to the drug or placebo during the trial. The patients in the melatonin group received 20 mg of omeprazole in the morning before breakfast plus 3 mg of sublingual melatonin at night. In the placebo group, the patients received 20 mg of omeprazole in the morning before breakfast plus melatonin placebo sublingually at night.This study was performed on patients with mild to moderate symptoms of GERD, who were referred to the gastroenterology clinic of Shahid Beheshti Hospital as outpatients. At baseline, the patients were explained about the study and the course of treatment, and volunteers signed written informed consent forms for participation in this study. The inclusion criteria were as follows: diagnosis of GERD; age above 18 years; having complaints of heartburn and or regurgitation 2 days or more per week; and a score ≤32 on the Frequency Scale for the Symptoms of GERD (FSSG). In this questionnaire, the symptoms associated with the severity of disease included heartburn, throat burning sensation, esophageal dysphagia, chest pain, and voice hoarseness, which were evaluated in 20 items and scored based on a 0-4 Likert scale, with higher scores indicating more severe symptoms.The exclusion criteria were as follows: history of sensitivity to omeprazole or melatonin; patients with reflux symptoms with diagnosis of peptic ulcer and duodenal ulcer on endoscopy; pregnant or breastfeeding women; current use of drugs causing transient lower esophageal sphincter relaxation (e.g., calcium channel blockers and nitrates); patients with Child-Pugh C cirrhosis; patients with severe renal damage (Acute Kidney Injury Network [AKIN] classification stage 3); shift workers; patients using medications with major interactions with omeprazole or melatonin (e.g., fluvoxamine); patients using alternative or traditional medicines concurrently; and patients with severe symptoms (FSSG score >32).After selecting eligible volunteers for the study, demographic characteristics, including sex, age, smoking habits, and body mass index (BMI), were recorded. Also, before treatment, FSSG and QOL scores were calculated for the patients. To evaluate QOL, the validated Persian version of Mayo-gastroesophageal reflux questionnaire was employed. This questionnaire was completed before and after the study to evaluate the QOL of the patients. It contained 25 items, with the scores ranging from 25 (the lowest QOL) to 175 (the highest QOL)At baseline, the patients received the training needed to optimize their lifestyle for controlling GERD symptoms (e.g., consuming food at low volumes, but higher frequencies per day, not consuming alcohol, not wearing tight clothes, and avoiding lower esophageal sphincter loosening foods). Next, patients in the 2 groups took the medication or placebo for 4 weeks. After 4 weeks, they would return to the gastroenterology clinic for reexamination. In the second visit, they completed the FSSG and GERQ. During 4 weeks, the patients were contacted at least once a week to inquire about their adherence to medications, as well as possible adverse drug reactions (ADRs). If ADRs were attributed to the drug or placebo, the patient was recommended to stop taking the drug or placebo and was excluded from the study.