Effect of Preoperative Melatonin on Quality of Recovery After Elective Laparoscopic Cholecystectomy

NCT07553143 | Not Yet Recruiting

• 1 other identifier: 3606/T/0026
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

Laparoscopic cholecystectomy is one of the most commonly performed abdominal surgical procedures worldwide. Although the widespread implementation of Enhanced Recovery after Surgery (ERAS) protocols has improved perioperative outcomes, many patients continue to experience postoperative pain, sleep disturbance, anxiety, nausea, and fatigue, symptoms that collectively impair overall quality of recovery (QoR). Melatonin, an endogenous hormone that regulates circadian rhythm, also possesses anxiolytic, analgesic, antioxidant, and anti-inflammatory properties, positioning it as a valuable perioperative adjunct. However, most previous studies have evaluated melatonin primarily for isolated outcomes such as sleep quality or anxiety. Its effect on comprehensive postoperative recovery, assessed using validated patient-reported outcome instruments, remains insufficiently explored, particularly in laparoscopic cholecystectomy populations and in South Asian clinical settings. This prospective, randomized, double-blind, placebo-controlled trial (the MEL-REC trial) aims to evaluate the effect of preoperative oral melatonin on postoperative quality of recovery in patients undergoing elective laparoscopic cholecystectomy under general anaesthesia. The study will be conducted in the Department of Anaesthesiology at Combined Military Hospital (CMH), Dhaka, Bangladesh, over a total study period of 18 months (January 2026 to June 2027), with patient recruitment planned for 8 months (May to December 2026) after taking approval from institutional review board. Eighty four adult patients aged 18-60 years with American Society of Anesthesiologists (ASA) physical status I-II will be randomly allocated in a 1:1 ratio into two equal groups (n = 42 per group) using computer-generated permuted block randomization with centralized pharmacy based allocation concealment. The melatonin group (Group M) will receive oral melatonin 6 mg administered 60 minutes before induction of anaesthesia and the placebo group (Group P) will receive an identical placebo tablet under the same conditions. Neither the participants, the treating anaesthesiologist, the outcome assessor, nor the data analyst will be aware of group allocation until database lock. All patients will receive a standardized anaesthesia and perioperative management protocol, including standardized postoperative analgesia. The primary outcome will be postoperative quality of recovery assessed using the Quality of Recovery-15 (QoR-15) score at 24 ± 2 hours after surgery. Secondary outcomes include postoperative sleep quality measured by the Richards-Campbell Sleep Questionnaire, change in preoperative anxiety (delta-VAS-A score), total opioid consumption during the first 24 hours expressed as intravenous morphine milligram equivalents, incidence of postoperative nausea and vomiting, and time to first rescue analgesic request. All postoperative outcomes will be assessed by a trained research assistant blinded to group allocation. Based on the available evidence, it is anticipated that patients receiving preoperative melatonin will demonstrate higher QoR-15 scores at 24 hours after surgery compared with the placebo group. The melatonin group is also expected to have improved postoperative sleep quality, reduced opioid consumption, and a greater reduction in preoperative anxiety. If a clinically meaningful benefit is confirmed, given its well established safety profile, low cost, and ease of oral administration, preoperative melatonin may represent a practical perioperative adjunct that can be readily incorporated into ERAS protocols for laparoscopic cholecystectomy. The trial will be prospectively registered in the Bangladesh Medical Research Council (BMRC) clinical trial registry or clinicaltrials.gov prior to recruitment.

Conditions

Laparoscopic Cholecystectomy; Opioid Consumption, Postoperative; Postoperative Sleep Quality; PONV in Laparoscopic Cholocystectomies; Postoperative Quality of Recovery; Preoperative Anxiety

Keywords

Postoperative Quality of Recovery; QoR-15; Melatonin; Laparoscopic Cholecystectomy

Outcome Measures

Primary Outcomes (1)

• Quality of Recovery-15 (QoR-15) total score

  Validated 15-item patient-reported outcome. Range 0-150; higher = better recovery. MCID = 6.0 points.

  24 ± 2 hours after surgery

Secondary Outcomes (5)

• Sleep quality

  Morning after surgery (approximately 16-24 hours post-op)

• Change in preoperative anxiety

  From 60 minutes pre-surgery to immediately before induction

• Total opioid consumption

  0-24 hours postoperatively

• Incidence of postoperative nausea and vomiting (PONV)

  0-24 hours postoperatively

• Time to first rescue analgesic request

  0-24 hours postoperatively, measured in minutes from end of surgery

Study Arms (2)

Melatonin Group

EXPERIMENTAL

Single oral tablet of melatonin 6 mg administered 60 minutes before induction of general anaesthesia

Drug: Melatonin (N-acetyl-5-methoxytryptamine)

Placebo Group

PLACEBO COMPARATOR

Single oral placebo tablet identical in appearance, administered 60 minutes before induction

Drug: Placebo

Interventions

Melatonin (N-acetyl-5-methoxytryptamine) DRUG

Oral melatonin 6 mg tablet, single dose, administered 60 ± 15 minutes before induction of general anaesthesia

Melatonin Group

Placebo DRUG

Oral placebo tablet identical in appearance, single dose, same timing

Placebo Group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-60 years
• American Society of Anesthesiologists (ASA) physical status I-II
• Scheduled for elective laparoscopic cholecystectomy under general anesthesia
• Able to understand and provide informed consent
• Willing to participate in the study and complete follow-up assessments
• Body mass index (BMI) 18-35 kg/m2

You may not qualify if:

• Known allergy or hypersensitivity to melatonin or placebo component
• Chronic use of opioids, sedatives, or hypnotics (regular use for ≥4 weeks prior to surgery)
• Current use of beta-adrenergic receptor antagonists (beta-blockers) (suppress endogenous melatonin secretion via inhibition of pineal β₁-adrenergic receptors)
• History of psychiatric disorders requiring ongoing pharmacological treatment
• Pregnancy or lactation
• Severe hepatic impairment (Child-Pugh class B or C), as melatonin undergoes extensive first-pass hepatic metabolism via CYP1A2
• Diagnosed obstructive sleep apnoea requiring continuous positive airway pressure
• Diagnosed circadian rhythm disorder (e.g., delayed sleep phase disorder, advanced sleep phase disorder) requiring medical management
• Use of exogenous melatonin supplements within 30 days prior to surgery
• Inability to complete study questionnaires due to language barrier or cognitive impairment
• History of substance abuse or dependence

Sponsors & Collaborators

• Armed Forces Medical Institute Bangladesh: lead

Study Sites (1)

Department of Anaesthesiology, Combined Military Hospital, Dhaka Cantonment,Dhaka

Dhaka, Dhaka Division, 1206, Bangladesh

Location

Related Links

• Ivry, M., Goitein, D., Welly, W., \& Berkenstadt, H. (2017). Melatonin premedication improves quality of recovery following bariatric surgery - a double blind placebo controlled prospective study. Surgery for obesity and related diseases :official journal
• Andersen, L. P., Gögenur, I., Rosenberg, J., \& Reiter, R. J. (2016). The Safety of Melatonin in Humans. Clinical drug investigation, 36(3), 169-175.
• Gao, Y., Chen, X., Zhou, Q., Song, J., Zhang, X., Sun, Y., Yu, M., \& Li, Y. (2022). Effects of Melatonin Treatment on Perioperative Sleep Quality: A Systematic Review and Meta-Analysis with Trial Sequential Analysis of Randomized Controlled Trials.
• Harpsøe, N. G., Andersen, L. P., Gögenur, I., \& Rosenberg, J. (2015). Clinical pharmacokinetics of melatonin: a systematic review. European journal of clinical pharmacology, 71(8), 901-909. https://doi.org/10.1007/s00228-015-1873-4
• Validation of the postoperative Quality of Recovery-15 questionnaire after emergency surgery and association with quality of life at three months
• Myles, P. S., \& Myles, D. B. (2021). An Updated Minimal Clinically Important Difference for the QoR-15 Scale. Anesthesiology, 135(5), 934-935. https://doi.org/10.1097/ALN.0000000000003977
• Stark, P. A., Myles, P. S., \& Burke, J. A. (2013). Development and psychometric evaluation of a postoperative quality of recovery score: the QoR-15. Anesthesiology, 118(6), 1332-1340. https://doi.org/10.1097/ALN.0b013e318289b84b
• Wang, Z., Li, Y., Lin, D., \& Ma, J. (2021). Effect of Melatonin on Postoperative Pain and Perioperative Opioid Use: A Meta-analysis and Trial Sequential Analysis. Pain practice : the official journal of World Institute of Pain, 21(2), 190-203.

MeSH Terms

Interventions

Melatonin

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Central Study Contacts

Ahsan Habib Noman, Major

CONTACT

+8801769051441; ahsanhabibnoman777@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Graded Specialist & MD Phase B Resident, Principal Investigator

Study Record Dates

• First Submitted: April 21, 2026
• First Posted: April 27, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: May 5, 2026

Record last verified: 2026-04

Locations

BA (1)