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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 : January 10, 2020
Sponsor:
Information provided by (Responsible Party):
The University of Hong Kong

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.


Condition or disease Intervention/treatment Phase
Effect of Drugs Drug: Melatonin Drug: Dexamethasone Sodium Sulphate 4mg/1mL Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 87 participants
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
Official Title: The Effect of Melatonin on Postoperative Pain Reduction After Orthognathic Surgery
Estimated Study Start Date : January 2020
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : January 2023


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 Name: 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 Name: Decadron




Primary Outcome Measures :
  1. Subjective pain perception [ Time Frame: 14 days ]
    Self-reported pain level by numerical rating scale

  2. Total analgesic consumption [ Time Frame: 14 days ]
    Total amount of postoperative analgesic consumed


Secondary Outcome Measures :
  1. Time to first analgesic [ Time Frame: 1 day ]
    Time for patient to request for first dose of analgesic after the surgery (mins)

  2. Plasma levels of melatonin [ Time Frame: 16 days ]
    Plasma levels of melatonin (pg/mL)

  3. Plasma levels of inflammatory markers [ Time Frame: 16 days ]
    IL-6 and IL-10 (pg/mL)

  4. Plasma levels of hydrogen peroxide [ Time Frame: 16 days ]
    Plasma levels of hydrogen peroxide (µM)

  5. 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)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03995004


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

Sponsors and Collaborators
The University of Hong Kong
Investigators
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Principal Investigator: Winnie WS CHOI, PhD, MDS The University of Hong Kong

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Responsible Party: The University of Hong Kong
ClinicalTrials.gov Identifier: NCT03995004    
Other Study ID Numbers: UW 19-221
First Posted: June 21, 2019    Key Record Dates
Last Update Posted: January 10, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by The University of Hong Kong:
melatonin
orthognathic
pain
surgery
Additional relevant MeSH terms:
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Pain, Postoperative
Postoperative Complications
Pathologic Processes
Pain
Neurologic Manifestations
Signs and Symptoms
Dexamethasone
Dexamethasone acetate
Melatonin
Sodium sulfate
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antioxidants
Protective Agents
Central Nervous System Depressants
Cathartics