Analgesic and Antioxidant Effects of Melatonin in Pediatric Surgery

NCT06724432 | Completed

• 1 other identifier: ethics committee 125222022
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 2

Brief Summary

Background. Long-term consequences of postoperative pain are detrimental in children. We tested the hypothesis that melatonin reduces postoperative pain and oxidative stress involving sirtuin pathway in children undergoing surgery. Methods. Thirty-one children were randomly assigned to oral supplementation with melatonin or placebo, before surgery. Plasma levels of 4-hydroxynonenal (4-HNE), melatonin, sirtuin 1 (SIRT1), and circulating miR-34 and miR-124a were analyzed at T0 (pre-hospitalization), T1 (before surgery), and T2 (1 h after the end of the surgery).

Conditions

Postoperative Pain; Oxidative Stress Response

Keywords

children; surgery; postoperative pain; analgesia; melatonin; 4-hydroxynonenal (4-HNE); sirtuin 1 (SIRT1); miR-34; miR-124a

Outcome Measures

Primary Outcomes (1)

• Plasma levels evaluation of 4-hydroxynonenal (4-HNE), melatonin, sirtuin 1 (SIRT1), and circulating miR-34 and miR-124a

  Melatonin plasma levels were assessed using a competitive enzyme-linked immunosorbent assay (cELISA) kit from Antibodies.com (A87093) according to the manufacturer's instructions. 4-Hydroxynonenal (4-HNE) as a marker of lipid peroxidation was measured to evaluate OS by using a cELISA kit from Antibodies.com (A86962). SIRT1 was quantified using an ELISA kit from Invitrogen (EH427RB). MicroRNAs (miR-34 and miR-124a) were isolated from plasma using the Norgen total RNA isolation kit13.The Plasma microRNAs and spike-in cel-miR-39 expressions were evaluated using the TaqMan miRNA assay.

  Samples of 0.2 mL of plasma were collected at T0 (pre-hospitalization, 1 day before surgery), T1 (before surgery, pre-anesthesia) and T2 (at 1 h after the end of the surgery and awakening after anesthesia), and biochemical analyses performed.

Secondary Outcomes (1)

• control post operative pain in children treated with melatonin compared to placebo

  48 hours after surgery were considered as post-operative period

Study Arms (2)

Melatonin arm

EXPERIMENTAL

Mel treated children receive a single dose of oral melatonin 0.5 mg/kg (for a max 10 mg). Melatonin (Dicoson, Dicofarm, Italy) is prepared by a dedicated resident in a fixed volume of 5 mL by adding water to a syringe without a needle.

Drug: oral melatonin

Control arm

PLACEBO COMPARATOR

Children in the Control group receive 5 ml of 5% dextrose solution.

Drug: Placebo

Interventions

oral melatonin DRUG

Melatonin treated children receive a single dose of oral melatonin 0.5 mg/kg (for a max 10 mg) in a fixed volume of 5 mL of water , 1 hour before induction of anesthesia for surgery

Melatonin arm

Placebo DRUG

Children in the Control group receive 5 ml of 5% dextrose solution once 1 hour before induction of anesthesia

Control arm

Eligibility Criteria

• Age: 3 Years - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Children between 3 and 5 years of age scheduled for elective surgery, parental consent

You may not qualify if:

• Children with cerebral malformations and/or injuries, or surgery in the afternoon or at night to eliminate conditions that could affect melatonin production, or denial of parental consent

Sponsors & Collaborators

• University of Parma: lead
• University of Messina: collaborator
• University of Florida: collaborator
• University of Siena: collaborator
• University of Urbino "Carlo Bo": collaborator

Study Sites (2)

University Hospital of Messina, Italy

Messina, 98125, Italy

Location

Neonatology Unit, Department of Medicine and Surgery, University of Parma, Pietro Barilla Children's Hospital

Parma, 43126, Italy

Location

MeSH Terms

Conditions

Pain, Postoperative; Agnosia

Interventions

Melatonin

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Perceptual Disorders; Neurobehavioral Manifestations; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: children were randomly assigned to oral supplementation with melatonin or placebo (5% dexstrose), before induction of an anesthesia for surgery

Study Record Dates

• First Submitted: December 4, 2024
• First Posted: December 9, 2024
• Study Start: June 1, 2021
• Primary Completion: June 1, 2023
• Study Completion: September 1, 2024
• Last Updated: December 17, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2)