Zybach Katherine, Friesen Craig A, Schurman Jennifer V
Katherine Zybach, Craig A Friesen, Division of Gastroenterology, Hepatology and Nutrition, Children's Mercy Kansas City, Kansas City, MO 64108, United States.
World J Gastrointest Pharmacol Ther. 2016 Feb 6;7(1):156-61. doi: 10.4292/wjgpt.v7.i1.156.
To study the effectiveness of melatonin vs placebo in children with functional dyspepsia (FD).
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.
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).
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.
研究褪黑素与安慰剂对功能性消化不良（FD）儿童的疗效。
本研究为双盲、随机、安慰剂对照交叉试验。受试者年龄在8至17岁之间，根据罗马III标准诊断为FD。所有受试者在接受4周抑酸治疗后均无反应。受试者按对参与者和研究团队均保密的顺序，连续两周接受安慰剂治疗，然后连续两周接受褪黑素治疗。通过整体临床评分评估腹痛变化。疼痛程度由受试者自我报告，分别为加重（1级）、无变化（2级）、中度改善（3级）、良好（4级；轻微疼痛且不影响日常活动）或极佳（5级；无疼痛）。阳性临床反应定义为3级或更高等级的反应。受试者在一周基线期及每个治疗期佩戴活动记录仪以评估睡眠情况。在整个研究期间记录受试者的睡眠潜伏期和总睡眠时间。
共招募14名受试者，12名完成研究。1名在开始褪黑素和安慰剂治疗前退出，另1名在开始褪黑素治疗前退出。接受褪黑素治疗的受试者中42%获得阳性临床反应（3 - 5级），接受安慰剂治疗的受试者中这一比例为50%（无统计学差异）。计算效应量显示Cohen's D为0.343，表明有利于安慰剂的中等效应。接受褪黑素治疗的4名患者和接受安慰剂治疗的5名患者出现4级或5级反应。基线睡眠参数处于健康范围内，最长睡眠潜伏期略超过20分钟（平均7.46 ± 8.53分钟），最短睡眠时间略超过7小时（平均10.09 ± 2.72小时）。与安慰剂治疗期相比，褪黑素治疗期的平均潜伏期无差异（4.48 ± 6.45分钟对3.58 ± 4.24分钟；无统计学差异）。与安慰剂治疗期相比，褪黑素治疗期的平均睡眠时间无差异（9.90 ± 3.53小时对9.41 ± 2.70小时；无统计学差异）。
褪黑素似乎对未经筛选的儿童FD患者缓解疼痛无效。未来研究应考虑FD亚型、病理生理机制和基线睡眠障碍。
