μ-opioid Receptor Polymorphism and Opioid Analgesia

Observational Study: The Effect of μ-opioid Receptor Genetic Polymorphism on Neuraxial Opioid Labor Analgesia

In this prospective observational double-blind study, the investigators aim to assess the effect of the single nucleotide polymorphism of the μ-opioid receptor gene (OPRM1, p.118A/G) on the duration of epidural fentanyl labor analgesia.

Study Overview

• Status: Completed
• Conditions: Pharmacogenetic and Duration of Labor Fentanyl Analgesia
• Intervention / Treatment: Drug: Fentanyl

Detailed Description

The single nucleotide polymorphism (SNP), p.118A/G of the µ -opioid receptor gene (OPRM1), may alter pain perception and individual response to opioid analgesia. This SNP leads to a variant µ-opioid receptor in which an asparagine is substituted for aspartate as the 102nd amino acid of the receptor protein (p.Asn102Asp). At the investigators' institution, it is common practice to initiate labor analgesia with epidural fentanyl. No data are available to determine how the µ-opioid polymorphism affects pain perception and response to opioids, such as fentanyl, in the investigators' population. The investigators aim to assess the effect of the single nucleotide polymorphism of the µ-opioid receptor gene (OPRM1, p.118A/G) on duration of epidural fentanyl labor analgesia.

This is a prospective observational and double-blind study. Before initiation of epidural labor analgesia, venous blood will be drawn into coded EDTA tubes. DNA isolation and genotyping of OPRM1:p.118A/G will be performed at the American University of Beirut. In 250 parturients, labor epidural analgesia will be initiated with 100 µg of epidural fentanyl following a test dose of lidocaine and epinephrine. No drugs will be injected until second request of analgesia. Patients will be divided into two groups based on their genetic groups: Group A consists of wild-type homozygote (A118), and Group G includes heterozygote and homozygote carrying the G118 allele. Duration of fentanyl analgesia (primary outcome) will be compared. Data will be presented as a mean ± SD or numbers and percentages. Statistical analysis will be performed with the Student's t-test, Chi-square or Fisher's exact test as appropriate. P value <0.05 will be considered significant.

• Study Type: Observational
• Enrollment (Actual): 250

Contacts and Locations

Study Locations

• Lebanon
  • Beirut, Lebanon
    • American University of Beirut

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Nulliparous parturients ≥ 37 weeks gestation, with ASA I or II, with an uncomplicated course of singleton vertex pregnancy requesting epidural analgesia for pain relief

Description

Inclusion Criteria:

• Nulliparous parturients ≥ 37 weeks gestation, with ASA I or II, with an uncomplicated course of singleton vertex pregnancy (in spontaneous labor or with spontaneous rupture of membrane), requesting epidural analgesia for pain relief

Exclusion Criteria:

• Advanced cervical dilation (> 5 cm) at the time of request for epidural analgesia
• Severe medical or obstetric complications (preeclampsia, uncontrolled pregestational diabetes, etc…)
• Multiple gestation
• Contraindication to epidural analgesia
• Local anesthetics or fentanyl allergy
• History of chronic opioid use or recent acute opioid use.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Nulliparous requesting epidural; Nulliparous parturients ≥ 37 weeks gestation, with ASA I or II, with an uncomplicated course of singleton vertex pregnancy requesting epidural analgesia for pain relief will be included. When the patient requests analgesia, cervical dilatation will be verified by the obstetric resident/attending. Then epidural analgesia will be initiated with a test dose of 3mL of 2% lidocaine and epinephrine 15 µg and a dose of fentanyl 100 µg diluted to a total volume of 10 mL with preservative- free normal saline. Before placement of the epidural, venous blood (2 mL) will be drawn into special tubes. Genotyping of OPRM1: p.118A/G will be also performed.

Drug: Fentanyl; Epidural analgesia will be initiated with 100µg of epidural fentanyl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of epidural fentanyl	The primary outcome variable is duration of epidural fentanyl for labor analgesia.	up to 24h

Secondary Outcome Measures

Outcome Measure	Time Frame
VAS at request for analgesia	up to 24h
Cervical dilation at request for analgesia	up to 24h
Incidence of pruritus, nausea, and vomiting.	up to 24h

Collaborators and Investigators

• Sponsor: American University of Beirut Medical Center
• Investigators: Principal Investigator: Sahar Siddik Sayyid, MD, American Univesity of Beirut

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: March 25, 2014
• First Submitted That Met QC Criteria: March 27, 2014
• First Posted (Estimate): March 31, 2014

Study Record Updates

• Last Update Posted (Actual): February 22, 2018
• Last Update Submitted That Met QC Criteria: February 20, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: Labor analgesia; Opioids; Opioid analgesia; µ-opioid receptor polymorphism
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Perceptual Disorders; Agnosia; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Fentanyl
• Other Study ID Numbers: ANES.SS.11

Plan for Individual participant data (IPD)

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