The Effect of Melatonin on Postoperative Pain Reduction After Orthognathic Surgery

• ClinicalTrials.gov Identifier: NCT03995004
• Recruitment Status: Not yet recruiting
• First Posted: June 21, 2019
• Last Update Posted: November 4, 2020
• Sponsor: The University of Hong Kong
• Information provided by (Responsible Party): The University of Hong Kong

Tracking Information

• First Submitted Date: June 20, 2019
• First Posted Date: June 21, 2019
• Last Update Posted Date: November 4, 2020
• Estimated Study Start Date: January 2021
• Estimated Primary Completion Date: February 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 20, 2019)

• Subjective pain perception [ Time Frame: 14 days ]
  Self-reported pain level by numerical rating scale
• Total analgesic consumption [ Time Frame: 14 days ]
  Total amount of postoperative analgesic consumed

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 7, 2020)

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

Original Secondary Outcome Measures (submitted: June 20, 2019)

• Time to first analgesic [ Time Frame: 1 day ]
  Time for patient to request for first dose of analgesic after the surgery
• Plasma levels of melatonin [ Time Frame: 16 days ]
  Plasma levels of melatonin
• Plasma levels of inflammatory markers and hydrogen peroxide [ Time Frame: 16 days ]
  IL-6 and IL-10
• Plasma levels of hydrogen peroxide [ Time Frame: 16 days ]
  Plasma levels of hydrogen peroxide
• Plasma levels and activities of antioxidative enzymes [ Time Frame: 16 days ]
  superoxide dismutase, catalase, and glutathione peroxidase

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The Effect of Melatonin on Postoperative Pain Reduction After Orthognathic Surgery
• Official Title: The Effect of Melatonin on Postoperative Pain Reduction After Orthognathic Surgery

Brief Summary

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.

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
• Study Phase: Phase 1

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

M: Oral Melatonin 10mg / IV Normal Saline D: Placebo cap / IV Dexamethasone 4mg DM: Oral Melatonin 10mg / IV Dexamethasone 4mg

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Identical capsules for melatonin and placebo Clear fluid of the same volume for IV dexamethasone vs normal saline

Primary Purpose: Treatment

• Condition: Effect of Drugs

Intervention

• 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 Name: Decadron

Study Arms

• 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.

  Intervention: Drug: Melatonin
• 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

  Intervention: Drug: Dexamethasone Sodium Sulphate 4mg/1mL
• 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

  Interventions:

  • Drug: Melatonin
  • Drug: Dexamethasone Sodium Sulphate 4mg/1mL

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: June 20, 2019): 87
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2024
• Estimated Primary Completion Date: February 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Winnie WS CHOI, PhD, MDS; +85228590266; drwchoi@hku.hk

• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT03995004
• Other Study ID Numbers: UW 19-221
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: The University of Hong Kong
• Study Sponsor: The University of Hong Kong
• Collaborators: Not Provided

Investigators

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

• PRS Account: The University of Hong Kong
• Verification Date: April 2020