Clinical trial NCT03995004: The Effect of Melatonin on Postoperative Pain Reduction After Orthognathic Surgery
Official title: The Effect of Melatonin on Postoperative Pain Reduction After Orthognathic Surgery
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE1
Conditions: Effect of Drugs
Keywords: melatonin
orthognathic
pain
surgery
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
First posted: 2019-06-21
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: M: Oral Melatonin 10mg / IV Normal Saline D: Placebo cap / IV Dexamethasone 4mg DM: Oral Melatonin 10mg / IV Dexamethasone 4mg
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Subjective pain perception
timeFrame: 14 days
measure: Total analgesic consumption
timeFrame: 14 days
Secondary outcomes:
measure: Time to first analgesic
timeFrame: 1 day
measure: Plasma levels of melatonin
timeFrame: 16 days
measure: Plasma levels of inflammatory markers
timeFrame: 16 days
measure: Plasma levels of hydrogen peroxide
timeFrame: 16 days
measure: Plasma levels and activities of antioxidative enzymes
timeFrame: 16 days
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Prince Philip Dental Hospital
Study officials:
affiliation: The University of Hong Kong
name: Winnie WS CHOI, PhD, MDS
role: PRINCIPAL_INVESTIGATOR
References: