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The Effect of Melatonin on Postoperative Pain Reduction After Orthognathic Surgery

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

Tracking Information
First Submitted Date  ICMJE June 20, 2019
First Posted Date  ICMJE June 21, 2019
Last Update Posted Date November 4, 2020
Estimated Study Start Date  ICMJE January 2021
Estimated Primary Completion Date February 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE
 (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  ICMJE The Effect of Melatonin on Postoperative Pain Reduction After Orthognathic Surgery
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE 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  ICMJE Effect of Drugs
Intervention  ICMJE
  • 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  ICMJE
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: June 20, 2019)
87
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2024
Estimated Primary Completion Date February 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Winnie WS CHOI, PhD, MDS +85228590266 drwchoi@hku.hk
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03995004
Other Study ID Numbers  ICMJE 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  ICMJE
Plan to Share IPD: No
Responsible Party The University of Hong Kong
Study Sponsor  ICMJE The University of Hong Kong
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Winnie WS CHOI, PhD, MDS The University of Hong Kong
PRS Account The University of Hong Kong
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP