COMT and OPRM1 Polymorphisms and Their Effect on Post-Operative Pain in Children

COMT and OPRM1 Polymorphisms and Their Effect on Post-Operative Pain in Children Undergoing Orthopedic, Abdominal, Thoracic, and Plastic Surgeries.

The goal of this observational study is to investigate whether the A118G single-nucleotide polymorphism (SNP) in the mu-opioid receptor1(OPRM1) and Catechol-O-methyltransferase (COMT) SNPs influence postoperative pain scores in children between the ages of 8 and 18 undergoing orthopedic, abdominal, thoracic, and plastic surgeries.

The main question[s] it aims to answer [is]:

Do OPRM1 and COMT SNPs influence postoperative pain scores in children between the ages of 8 and 18 undergoing orthopedic, abdominal, thoracic, and plastic surgeries?

Participants will be assessed for their pain scores, sedation level, the amount of postoperative analgesics received, duration of their stay in the post-anesthesia care unit, and toxicity.

Study Overview

• Status: Recruiting
• Conditions: Pain; Children, Only; Genetic Change

Detailed Description

Inadequately treated pain in children undergoing surgery is a major concern for health providers. Recent evidence indicates that pain sensitivity differs among races and ethnicities and genetic makeup. Catechol-O-methyltransferase (COMT) polymorphisms (rs6269, rs4633, rs4818 and rs4680) which are inherited together in different phenotypes influence clinical presentations and responses to pain.

A118G single-nucleotide polymorphism (SNP) in the mu-opioid receptor1 (OPRM1) gene is associated with differences in pain perception and opioid requirements. The effect of genome variations in the COMT gene and in the OPRM1 on postoperative pain perception and morphine analgesia in children needs further exploration. The main objective of this study was to investigate whether the OPRM1 and COMT SNPs influence postoperative pain scores in children between the ages of 8 and 18 undergoing orthopedic, abdominal, thoracic, and plastic surgeries. Secondary objective includes assessing whether OPRM1 and COMT SNPs influence postoperative sedation score, intraoperative and postoperative opioid requirements, length of stay in the post anesthesia care unit (PACU), and signs of respiratory depression (RD) and postoperative nausea and vomiting (PONV).

Methodology: A prospective cohort genotype-blinded observational study will be conducted. A convenience sample of 200 children between the ages of 8-18 undergoing orthopedic, abdominal, thoracic, and plastic surgeries will be recruited from the American University of Beirut Medical Center (AUBMC). The primary outcome of the study is the post operative pain score in PACU.

Secondary outcomes include the postoperative sedation score, intraoperative and postoperative opioid requirements, length of stay in the PACU, and signs of RD and PONV. To test the hypothesis that COMT and OPRM1 SNPs are associated with postoperative analgesia outcomes in children, SPSS version 29 will be used. Allelic and genotype frequencies will be examined by the Hardy-Weinberg equilibrium (HWE) test. To analyze the association between the different genetic variations and the outcomes, bivariate analysis will be performed. Variables measured over time will be compared between the groups using an exploratory mixed model analysis. Time to first post-operative opioid requirement will be analyzed using the survival analysis Kaplan Meier curve. Such understanding will pave the way for individual tailoring and optimization of pain assessment and management in children undergoing orthopedic, abdominal, thoracic, and plastic surgical procedures.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Roland Kaddoum, MD; Phone Number: 6380 01350000; Email: rk16@aub.edu.lb
• Study Contact Backup: Name: Thouraya HajAli; Phone Number: 5738 01350000; Email: th64@aub.edu.lb

Study Locations

• Lebanon
  • Beirut, Lebanon
    • Recruiting
    • Roland Kaddoum
    • Contact: Roland Kaddoum, MD; Email: rk16@aub.edu.lb

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Children between the ages of 8-18 undergoing orthopedic, abdominal, thoracic, and plastic surgeries will be recruited from the American University of Beirut Medical Center (AUBMC).

Description

Inclusion Criteria:

• All children 8 years to 18 years
• Undergoing orthopedic, abdominal, thoracic, and plastic surgeries
• American Society of Anesthesiologists classification (ASA) I-II-III

Exclusion Criteria:

• Children with schizoid personality disorders, phobias, and anxiety
• Patients with neuropathic pain associated with surgeries requiring surgical treatment.
• Children presented with all types of depressive disorders, atypical bipolar disorder, or a suspicion of substance abuse.
• American Society of Anesthesiologists classification (ASA) ≥IV
• All patients receiving regional anesthesia, local blocks, epidural and caudal blocks.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain scores	Pain scores measured using the Numerical Rating Scale (NRS) (ranging from 0 to 10, with 0 no pain and 10 worst pain)	Until discharge from PACU (about 3 hours)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative sedation	Postoperative sedation measured using the Richmond Agitation Sedation Scale (RASS) (ranging from -5 to +4, with -5 unarousable and +4 combative)	Until discharge from PACU (about 3 hours)
Use of intraoperative and post-operative opioids	Use of intraoperative and post-operative opioids (Yes/No)	Until discharge from PACU (about 3 hours)
Length of post-anesthesia care unit (PACU) stay	Length of post-anesthesia care unit (PACU) stay measured in hours	Until discharge from PACU (about 3 hours)
Postoperative respiratory depression	Postoperative respiratory depression (Yes/No)	Until discharge from PACU (about 3 hours)
Postoperative nausea and vomiting	Postoperative nausea and vomiting (Yes/No)	Until discharge from PACU (about 3 hours)

Collaborators and Investigators

• Sponsor: American University of Beirut Medical Center
• Investigators: Principal Investigator: Roland Kaddoum, MD, American University of Beirut Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2025
• Primary Completion (Estimated): January 13, 2027
• Study Completion (Estimated): January 13, 2027

Study Registration Dates

• First Submitted: January 9, 2025
• First Submitted That Met QC Criteria: January 10, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 14, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Postoperative Complications; Pathologic Processes; Pain, Postoperative
• Other Study ID Numbers: BIO-2024-0365

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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