Randomized Controlled Trial
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pharmacol Ther. Feb 6, 2016; 7(1): 156-161
Published online Feb 6, 2016. doi: 10.4292/wjgpt.v7.i1.156
Therapeutic effect of melatonin on pediatric functional dyspepsia: A pilot study
Katherine Zybach, Craig A Friesen, Jennifer V Schurman
Katherine Zybach, Craig A Friesen, Division of Gastroenterology, Hepatology and Nutrition, Children’s Mercy Kansas City, Kansas City, MO 64108, United States
Jennifer V Schurman, Division of Developmental and Behavioral Sciences, Children’s Mercy Kansas City, Kansas City, MO 64108, United States
Author contributions: Zybach K was the primary contributor to study design, study management, data analysis, and manuscript writing and revision; Friesen CA contributed to study design, analysis, and manuscript writing and revision; Schurman JV contributed to analysis, manuscript writing, and critical review.
Institutional review board statement: The study was reviewed and approved by the Children’s Mercy Hospital Institutional Review Board.
Clinical trial registration statement: This study is registered at ClinicalTrials.gov (NCT00148603).
Informed consent statement: The legal guardians of all study participants provided informed written consent and all study participants provided assent prior to study enrollment.
Conflict-of-interest statement: The authors have no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Craig A Friesen, MD, Division of Gastroenterology, Hepatology and Nutrition, Children’s Mercy Kansas City, 2401 Gillham Road, Kansas City, MO 64108, United States. cfriesen@cmh.edu
Telephone: +1-816-2343016 Fax: +1-816-8021465
Received: August 8, 2015
Peer-review started: August 11, 2015
First decision: September 11, 2015
Revised: October 6, 2015
Accepted: November 23, 2015
Article in press: November 25, 2015
Published online: February 6, 2016
Processing time: 174 Days and 11.6 Hours
Abstract

AIM: To study the effectiveness of melatonin vs placebo in children with functional dyspepsia (FD).

METHODS: The study was conducted as a double blind, randomized, placebo controlled crossover trial. Subjects were aged 8-17 years and diagnosed with FD based on Rome III criteria. All subjects had failed to respond to 4 wk of acid suppression. Subjects receive a continuous two weeks of placebo and a continuous two weeks of melatonin in an order blinded to the participant and the study team. A Global Clinical Score was obtained to assess changes in abdominal pain. Pain was self-reported to be worse (grade 1), no change (grade 2), moderate improvement (grade 3), good (grade 4; minimal pain and not interfering with daily activities), or excellent (grade 5; no pain), respectively. A positive clinical response was defined as a grade 3 or greater response. Subjects wore an actigraph to assess sleep during a one week baseline period and during each treatment period. Subjects’ sleep latency and total sleep time were recorded throughout the duration of the study.

RESULTS: Fourteen subjects were enrolled and 12 completed the study. One withdrew prior to starting both melatonin and placebo and the other before starting melatonin. A positive clinical response (grade 3-5) was achieved in 42% of subjects on melatonin vs 50% of subjects on placebo (NS). Effect size was calculated and revealed a Cohen’s D of 0.343 which demonstrates a medium effect favoring placebo. A grade 4 or grade 5 response was seen in 4 patients on melatonin and 5 patients on placebo. Baseline sleep parameters were in the healthy range with the longest sleep latency being just over 20 min (mean 7.46 ± 8.53 min) and the shortest sleep duration just over 7 h (mean 10.09 ± 2.72 h). The mean latency did not differ between periods of treatment with melatonin as compared to placebo (4.48 ± 6.45 min vs 3.58 ± 4.24 min; NS). The mean sleep duration did not differ between periods of treatment with melatonin as compared to placebo (9.90 ± 3.53 h vs 9.41 ± 2.70 h; NS).

CONCLUSION: Melatonin does not appear to have efficacy in relieving pain in unselected pediatric FD. Future studies should consider FD subtypes, pathophysiologic mechanisms, and baseline sleep disturbances.

Keywords: Melatonin; Abdominal pain; Functional dyspepsia; Sleep latency; Sleep duration; Actigraphy

Core tip: Medical therapy is limited in children with functional dyspepsia. This creates a challenging clinical dilemma with regards to managing their symptoms. Melatonin has been shown to have a positive effect on pain in adults with functional dyspepsia or irritable bowel syndrome, independent of its effects on sleep. To date, there have been no studies to evaluate the effect of melatonin on abdominal pain in children. In the current study, melatonin did not result in improvement in abdominal pain or sleep parameters in children with functional dyspepsia.