TY - JOUR
T1 - Effect of melatonin in patients with low anterior resection syndrome (MELLARS)
T2 - a study protocol for a randomised, placebo-controlled, crossover trial
AU - Zahid, Jawad Ahmad
AU - Madsen, Michael Tvilling
AU - Bulut, Orhan
AU - Christensen, Peter
AU - Gögenur, Ismail
N1 - © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2023/9/11
Y1 - 2023/9/11
N2 - 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).
AB - 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).
KW - Humans
KW - Cross-Over Studies
KW - Low Anterior Resection Syndrome
KW - Melatonin/pharmacology
KW - Postoperative Complications
KW - Quality of Life
KW - Randomized Controlled Trials as Topic
KW - Rectal Neoplasms
KW - SLEEP MEDICINE
KW - Colorectal surgery
KW - GASTROENTEROLOGY
UR - http://www.scopus.com/inward/record.url?scp=85170626758&partnerID=8YFLogxK
U2 - 10.1136/bmjopen-2022-067763
DO - 10.1136/bmjopen-2022-067763
M3 - Journal article
C2 - 37696629
SN - 2399-9772
VL - 13
SP - e067763
JO - BMJ Paediatrics Open
JF - BMJ Paediatrics Open
IS - 9
M1 - e067763
ER -