褪黑素对低位前切除综合征患者的影响（MELLARS）：一项随机、安慰剂对照、交叉试验的研究方案。

Effect of melatonin in patients with low anterior resection syndrome (MELLARS): a study protocol for a randomised, placebo-controlled, crossover trial.

机构信息

Center for Surgical Science, Department of Surgery, Zealand University Hospital, Køge, Denmark

Center for Surgical Science, Department of Surgery, Zealand University Hospital, Køge, Denmark.

出版信息

BMJ Open. 2023 Sep 11;13(9):e067763. doi: 10.1136/bmjopen-2022-067763.

DOI:10.1136/bmjopen-2022-067763

PMID:37696629

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10496695/

Abstract

INTRODUCTION

After rectal cancer surgery, a majority of patients suffer from sequelae known as low anterior resection syndrome (LARS). It is a collection of symptoms consisting of flatus and/or stool incontinence, evacuation frequency, re-evacuation and urgency. The circadian hormone, melatonin, has shown to possess anti-inflammatory properties, and in high doses, it reduces bowel movements. The aim of the study is to investigate if locally administered melatonin has an alleviating effect on LARS. Secondarily, the effect of melatonin on bowel movements, other patient-reported symptoms, quality of life, depression, anxiety, sleep disturbances, motilin levels and rectal mucosa histology will be examined.

METHODS AND ANALYSIS

This is a randomised, placebo-controlled, double-blinded, two-period crossover trial. The participants are randomised to 28 days of 25 mg melatonin administered rectally via an enema daily (or placebo) followed by a 28-day washout and then 28 days of placebo (or melatonin). Three participants will be included in an internal feasibility test. They will receive 25 mg of melatonin daily for 28 days. Data from these participants will be used to assess the feasibility of the rectally administered melatonin and to analyse the course of recruitment and outcome measurements. Afterwards, 18 participants will be included in the crossover trial. The severity of the LARS symptoms will be evaluated using the LARS Score on the first and last day of each treatment period.

ETHICS AND DISSEMINATION

The Regional Ethics Committee, the Danish Medicines Agency and the Data and Development Support in Region Zealand approved this study. The study will be performed according to the Helsinki II declaration. Written informed consent will be obtained from all participants. The results of the study will be submitted to peer-reviewed journals for publication and presented at congresses.

TRIAL REGISTRATION NUMBERS

EudraCT Registry (2020-004442-11) and ClinicalTrial.gov Registry (NCT05042700).

摘要

简介

在直肠癌手术后，大多数患者会出现被称为低位前切除综合征（LARS）的后遗症。它是一组由气体和/或粪便失禁、排便频率、再排空和急迫感组成的症状。昼夜节律激素褪黑素具有抗炎特性，高剂量时可减少肠蠕动。本研究旨在探讨局部给予褪黑素是否对 LARS 有缓解作用。其次，将研究褪黑素对肠道运动、其他患者报告的症状、生活质量、抑郁、焦虑、睡眠障碍、胃动素水平和直肠黏膜组织学的影响。

方法和分析

这是一项随机、安慰剂对照、双盲、两周期交叉试验。参与者随机接受 28 天 25mg 褪黑素直肠给药（通过灌肠），每日一次（或安慰剂），然后进行 28 天洗脱期，再接受 28 天安慰剂（或褪黑素）。将有 3 名参与者纳入内部可行性测试。他们将每天接受 25mg 褪黑素治疗 28 天。这些参与者的数据将用于评估直肠给予褪黑素的可行性，并分析招募和结果测量的过程。之后，将有 18 名参与者纳入交叉试验。在每个治疗期的第一天和最后一天，使用 LARS 评分评估 LARS 症状的严重程度。