The Effect of Melatonin on Postoperative Pain Reduction After Orthognathic Surgery

Orthognathic surgery is a procedure performed to correct dentofacial deformities. It involves osteotomy at the facial skeleton. Considerable pain is expected in the early recovery period.

Melatonin is a hormone that is produced naturally by the body. Synthetic Melatonin is available over the counter for the management of sleeping disorder and jetlag. Clinically, Melatonin can also be used to reduce pain and analgesic consumption in patients undergoing surgery.

Dexamethasone is a type of steroid. It can suppress the inflammatory response. It is an anti-inflammatory, anti-allergic drug. It is commonly used in head and neck and oral surgery for its anti-inflammatory effect to reduce swelling.

This study aims evaluate the efficacy of oral melatonin in the pain reduction following orthognathic surgery.

This is a double-blinded randomized controlled trial. We will recruit 87 patients who are scheduled for double-jaw orthognathic surgery to participate in this three-year study. The study lasts for 2 weeks. Participant will be randomly allocated by computer to one of the three groups. (1) Group D will receive dexamethasone only; (2) Group M will receive melatonin only; and (3) Group DM both melatonin and dexamethasone.

Postoperative pain level and perioperative plasma levels of inflammatory markers and anti-oxidizing enzymes will be recorded and compared among the study groups.

Study Overview

• Status: Suspended
• Conditions: Effect of Drugs
• Intervention / Treatment: Drug: Melatonin; Drug: Dexamethasone Sodium Sulphate 4mg/1mL

Detailed Description

Melatonin (N-acetyl-5-methoxytryptamine) is a neurohormone that is endogenously produced and secreted by the pineal gland in the brain following a circadian rhythm, with a plasma concentration highest at night and lowest during the day.

The normal physiological roles of melatonin in the human body are to regulate diurnal rhythm, sleep, mood, immunity, reproduction, intestinal motility, and metabolism. Oral supplemental melatonin has been used in the management of jetlag and other sleep disorders. Recently, melatonin's analgesic, antioxidative, and neuroprotective properties have been highlighted in a number of animal models and a few human trials, although the exact cellular mechanism is still not yet clearly established. In surgical human trials, some conflicting data have been presented regarding the analgesic properties of exogenous melatonin supplement. Whilst the large proportion of studies showed that perioperative administration of melatonin yielded significantly positive effects in the reduction of postsurgical pain, and the reduction of overall morphine consumption, others demonstrated the opposite with no significant effects in pain experience. The reason for this could be related to the dosage, route of administration, and/or time of administration. To date, there is still no consensus on a standardized dosing regimen for melatonin. In non-surgical trials, melatonin has shown promising benefits in many degenerative diseases and conditions related to chronic inflammation and oxidative stress. Amongst many, the reported positive effects of melatonin ranged from the reduction of radiation dermatitis, control of signs and symptoms of ulcerative colitis, management of chronic retinopathy, and reduction of lung oxidative stress in chronic obstructive pulmonary disease patients.

Hypothesis:

Melatonin can significantly reduce postoperative pain after orthognathic surgery. Antioxidative enzyme activity and level will be elevated and the level of inflammatory markers are reduced. Melatonin has a synergistic effect with dexamethasone.

This is a double-blinded randomized controlled trial. We will recruit 87 patients who are scheduled for double-jaw orthognathic surgery to participate in this three-year study. The study lasts for 2 weeks. Participant will be randomly allocated by computer to one of the three groups. (1) Group D will receive dexamethasone only; (2) Group M will receive melatonin only; and (3) Group DM both melatonin and dexamethasone.

Postoperative pain level and perioperative plasma levels of inflammatory markers and anti-oxidizing enzymes will be recorded and compared among the study groups.

• Study Type: Interventional
• Enrollment (Anticipated): 87
• Phase: Phase 1

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Prince Philip Dental Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ASA Class I
• Age between 18 - 60 inclusive

Exclusion Criteria:

• Pregnancy
• Any pre-existing systemic condition
• Previous history of orthognathic surgery
• Adverse reaction or allergic to oral melatonin
• Need for distraction osteogenesis
• Patient with chronic pain
• Patients with known psychological disorders
• Currently taking oral steroid or anti-inflammatory medication or any analgesic

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Melatonin; Oral Melatonin 10mg at night time one day before the surgery and on the surgical day, and continued at bedtime on the surgical day, post-surgery day 1 and day 2. IV Normal Saline (1mL) on induction and continued q12h for 4 more doses.	Drug: Melatonin; Melatonin (N-acetyl-5-methoxytryptamine) is a neurohormone that is endogenously produced and secreted by the pineal gland in the brain following a circadian rhythm, with a plasma concentration highest at night and lowest during the day.
Active Comparator: Dexamethasone; Placebo capsules at night time one day before the surgery and on the surgical day, and continued at bedtime on the surgical day, post-surgery day 1 and day 2. IV Dexamethasone 4mg/1mL on induction and continued q12h for 4 more doses	Drug: Dexamethasone Sodium Sulphate 4mg/1mL; Dexamethasone is a glucocorticoid commonly used in orthognathic surgery to reduce postoperative facial edema by its potent anti-inflammatory effect; Other Names: Decadron
Experimental: Dexa_Melatonin; Oral Melatonin 10mg at night time one day before the surgery and on the surgical day, and continued at bedtime on the surgical day, post-surgery day 1 and day 2. IV Dexamethasone 4mg/1mL on induction and continued q12h for 4 more doses	Drug: Melatonin; Melatonin (N-acetyl-5-methoxytryptamine) is a neurohormone that is endogenously produced and secreted by the pineal gland in the brain following a circadian rhythm, with a plasma concentration highest at night and lowest during the day.; Drug: Dexamethasone Sodium Sulphate 4mg/1mL; Dexamethasone is a glucocorticoid commonly used in orthognathic surgery to reduce postoperative facial edema by its potent anti-inflammatory effect; Other Names: Decadron

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective pain perception	Self-reported pain level by numerical rating scale	14 days
Total analgesic consumption	Total amount of postoperative analgesic consumed	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first analgesic	Time for patient to request for first dose of analgesic after the surgery (mins)	1 day
Plasma levels of melatonin	Plasma levels of melatonin (pg/mL)	16 days
Plasma levels of inflammatory markers	IL-6 and IL-10 (pg/mL)	16 days
Plasma levels of hydrogen peroxide	Plasma levels of hydrogen peroxide (µM)	16 days
Plasma levels and activities of antioxidative enzymes	superoxide dismutase (U/mL), catalase ((nmol/min/mL), and glutathione peroxidase (nmol/min/mL)	16 days

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Investigators: Principal Investigator: Winnie WS CHOI, PhD, MDS, The University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2022
• Primary Completion (Anticipated): September 1, 2024
• Study Completion (Anticipated): September 1, 2024

Study Registration Dates

• First Submitted: June 20, 2019
• First Submitted That Met QC Criteria: June 20, 2019
• First Posted (Actual): June 21, 2019

Study Record Updates

• Last Update Posted (Actual): June 3, 2022
• Last Update Submitted That Met QC Criteria: May 31, 2022
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: pain; melatonin; surgery; orthognathic
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protective Agents; Antioxidants; Cathartics; Dexamethasone; Melatonin; Sodium sulfate
• Other Study ID Numbers: UW 19-221

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes