Comparing Two Doses of Oral Melatonin as Premedication in Children Undergoing Surgery

Comparing Two Doses of Oral Melatonin as Premedication in Children Undergoing Surgery: A Double-Blind Randomized Trial

Preoperative anxiety is a common issue in pediatric anesthesia. Children often experience anxiety and uneasiness due to uncertain outcomes. Surgery and anesthesia are among the most traumatic experiences for children, often considered anxiety-inducing medical treatments. Because they lack control over their environment and circumstances, children undergoing medical procedures typically experience significant unease or anxiety. Several studies have reported that 50%-80% of children experience preoperative anxiety.

In order to reduce kids anxiety intensity, several measures are utilized. These strategies are either pharmacological, psychological, or behavioural. Benzodiazepines are popular drugs that can reduce anxiety in children. The most used one in premedication is midazolam. It is a rapid-acting benzodiazepine that has a short elimination half-life. It has sedative, anxiolytic, hypnotic, and anterograde amnesic effects. Midazolam, on the other hand, might have a number of negative consequences, including paradoxical reactions, interactions with opioids, excessive sedation, disorientation, and reduced psychomotor performance.

Melatonin enhances anti-nociceptive effects, most prominently through the modulation of MT1/MT2 receptors in the brain and spinal cord. In addition, it has been demonstrated that melatonin can interact with additional receptors, including those in the GABAergic system, the nitric oxide (NO)arginine route, the N-Methyl-D-aspartate (NMDA) system, and the dopaminergic system, to produce anti-nociceptive and anti-allodynic effects.

Study Overview

• Status: Recruiting
• Conditions: Preoperative Anxiety
• Intervention / Treatment: Drug: melatonin (Circadin ®) 0.2 mg/kg; Drug: melatonin (Circadin ®) 0.4 mg/kg; Drug: placebo group

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Neveen Kohaf, Ph.D; Phone Number: 01060383012; Email: nevenabdo@azhar.edu.eg

Study Locations

• Egypt
  • Cairo Governorate
    • Cairo, Cairo Governorate, Egypt, 11765
      • Recruiting
      • Facualty of Pharmacy, Al Azhar University
      • Contact: Neveen Kohaf; Phone Number: 01060383012; Email: nevenabdo@azhar.edu.eg
      • Principal Investigator: Haider Hamza, M.D
• Iraq
  • Babel
    • Madīnat Bābil, Babel, Iraq, 51015
      • Recruiting
      • Al-Ayen Univerisity
      • Contact: Haider Hamza, M.D; Phone Number: +9647811593388; Email: hussein.hussein@alayen.edu.iq

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients of either sex
• age from 4 to 14 years
• Patients with American society Anesthesiologist physical status I and II
• Patients undergoing elective surgeries

Exclusion Criteria:

• ASA more than III
• Drug allergy.
• Gastrointestinal disorders.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1st group: melatonin 0.2 mg/kg group; patients will receive oral melatonin at a dose of 0.2 mg/kg	Drug: melatonin (Circadin ®) 0.2 mg/kg; Patients will receive oral melatonin at a dose of 0.2 mg/kg as premedication in the morning of the surgery, 90 minutes before the induction of anesthesia, with a maximum dose of melatonin set at 10 mg.
Active Comparator: 2nd group: M04 groupmelatonin 0.4 mg/kg group; patients will receive oral melatonin at a dose of 0.4 mg/kg	Drug: melatonin (Circadin ®) 0.4 mg/kg; Patients will receive oral melatonin at a dose of 0.4 mg/kg as premedication in the morning of the surgery, 90 minutes before the induction of anesthesia, with a maximum dose of melatonin set at 10 mg.
Placebo Comparator: 3rd group: placebo group; patients will receive oral placebo premedication	Drug: placebo group; Patients will receive oral placebo as premedication in the morning of the surgery, 90 minutes before the induction of anesthesia, with a maximum dose of melatonin set at 10 mg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
preoperative anxiety	The child's anxiety level will be assessed by Visual analogue scale-anxiety (VAS-A). The VAS-A consists of a 100 mm horizontal line; the left edge of the line is marked as "calm," while the other end shows "maximum anxiety." The patients were asked to assess their own anxiety and mark it on the anxiety line.	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
preoperative sedation	The sedation level will be assessed using Ramsay Sedation Scale. It divides a patient's level of sedation into six categories ranging from severe agitation at 1 to deep coma at 6.	24 hours

Collaborators and Investigators

• Sponsor: Al-Azhar University
• Collaborators: Al-Ayen Iraqi University
• Investigators: Principal Investigator: Neveen Kohaf, ph.d, Al-Azhar University

Study record dates

Study Major Dates

• Study Start (Estimated): July 12, 2026
• Primary Completion (Estimated): December 15, 2026
• Study Completion (Estimated): December 15, 2026

Study Registration Dates

• First Submitted: June 22, 2024
• First Submitted That Met QC Criteria: June 28, 2024
• First Posted (Actual): July 5, 2024

Study Record Updates

• Last Update Posted (Actual): January 6, 2026
• Last Update Submitted That Met QC Criteria: January 4, 2026
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: placebo; general anesthesia; premedication; preoperative anxiety; major surgery; oral melatonin
• Additional Relevant MeSH Terms: Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indoles; Tryptamines; Melatonin
• Other Study ID Numbers: 042/2021/Babel

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: data will be shared upon resealable request from the principal investigator
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No