Mu-Opioid Receptor Genetic Polymorphism and Intrathecal Analgesia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Cynthia Wong, Northwestern University
ClinicalTrials.gov Identifier:
NCT00418015
First received: December 31, 2006
Last updated: March 17, 2014
Last verified: March 2014
  Purpose

Pharmacogenetics has allowed clinicians to identify associations between an individual's genetic profile and his/her response to drugs. The A118G (c.188A>G)is a single nucleotide polymorphism (SNP) of the mu-opioid receptor (OPRM1). The mutated protein, N40D, appears to increase the binding affinity and potency of beta-endorphin approximately 3-fold. Individuals carrying the variant receptor gene (A118G) may show differences in some of the functions mediated by beta-endorphin action at the altered OPRM1. Combined spinal-epidural (CSE) analgesia is a commonly utilized technique for labor analgesia. Analgesia is initiated with the intrathecal administration of a lipid-soluble opioid (e.g. fentanyl), sometimes combined with a local anesthetic. The mean (± SD) duration of analgesia after intrathecal fentanyl 25 microgram was 89 ± 43 min. The ED50 of intrathecal fentanyl for labor analgesia varies between 14 microgram to 18.2 microgram. The wide variability in the duration of analgesia, as was well the differences in ED50 may result from differences known to affect labor pain (e.g., ethnicity, parity, stage of labor). Another possible explanation for the differences in opioid requirements and duration, as well as incidence of side effects such as itching and nausea/vomiting, is that opioid responsiveness is determined by genetic variability of the µ-opioid receptor. The ED50 for intrathecal fentanyl labor analgesia was significantly lower for parturients carrying the A118G variant of the mu-opioid receptor, compared to parturients with the A118 wild type receptor. The purpose of this study is to determine whether polymorphism at nucleotide 118 of OPRM1 influences the duration of intrathecal opioid (fentanyl) labor analgesia, and intrathecal opioid (morphine) postoperative analgesia.


Condition Intervention
Labor Pain
Post-cesarean Delivery
Procedure: Blood Draw

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Mu-Opioid Receptor Genetic Polymorphism and the Duration of Intrathecal Fentanyl Labor Analgesia. Mu-Opioid Receptor Genetic Polymorphism and the Efficacy of Postoperative Intrathecal Morphine Analgesia

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Duration of Intrathecal Fentanyl Analgesia [ Time Frame: Time (0-1440 minutes) to first analgesia request ] [ Designated as safety issue: No ]
    Time from intrathecal drug administration to request for analgesia either in laboring women of after cesarean delivery

  • Duration of Intrathecal Analgesia Following Cesarean Delivery [ Time Frame: 0 to 72 hours following cesarean delivery ] [ Designated as safety issue: No ]
    Time until request for supplemental analgesia following intrathecal morphine/fentanyl for cesarean delivery

  • Visual Analog Pain Scale (0 to 100) at Analgesia Request Following Intrathecal Intervention [ Time Frame: VAS at analgesia request ] [ Designated as safety issue: No ]
    Visual analog pain scale (0 to 100) at 1st request for supplemental analgesia


Secondary Outcome Measures:
  • Severity of Pruritus Following Fentanyl [ Time Frame: Labor analgesia ] [ Designated as safety issue: No ]
    Severity of pruritus during labor analgesia

  • Subjects With Pruritus at 24 Hours Post Morphine [ Time Frame: 24 hours post cesarean delivery ] [ Designated as safety issue: No ]
    Subjects reporting pruritus in the first 24 hours post cesarean delivery


Biospecimen Retention:   Samples With DNA

Blood Samples


Enrollment: 293
Study Start Date: October 2005
Study Completion Date: June 2007
Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Labor analgesia
Labor analgesia receiving fentanyl labor analgesia
Procedure: Blood Draw
Blood for OPRM1 analysis
Cesarean delivery analgesia
Cesarean delivery analgesia consisting of spinal fentanyl and morphine
Procedure: Blood Draw
Blood for OPRM1 analysis

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Pregnant women

Criteria

Inclusion Criteria:

Study 1: Laboring Women

  • Nulliparous women in spontaneous labor or with spontaneous rupture of membranes
  • Term pregnancy (≥ 37 weeks gestation)
  • Vertex presentation
  • Healthy, ASA PS 1-2
  • Desire neuraxial labor analgesia.

Study 2: Cesarean Delivery

  • Nulliparous women undergoing elective primary Cesarean delivery (e.g., for breech presentation, macrosomia)
  • Term pregnancy (≥ 37 weeks gestation)
  • Healthy, ASA PS 1-2
  • Desired spinal anesthesia.

Exclusion Criteria:

Study 1: Laboring Women

  • Chronic or pregnancy induced disease
  • Chronic opioid use
  • History of substance abuse
  • Systemic opioid analgesia before initiation of neuraxial labor analgesia
  • Cervical dilation < 2 cm or > 5 cm of time of request for neuraxial analgesia
  • Allergy to fentanyl

Study 2: Cesarean delivery

  • Chronic or pregnancy induced disease
  • Chronic opioid use
  • Previous abdominal or pelvic surgery
  • Allergy to fentanyl, morphine, or bupivacaine
  • BMI ≥ 40 kg/m2
  • History of substance abuse
  • Failed spinal anesthesia
  • Requirement for systemic opioid supplementation during Cesarean delivery.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00418015

Locations
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Northwestern University
Investigators
Principal Investigator: Cynthia A Wong, M.D. Northwestern University
  More Information

Publications:
Wong CA: Combined spinal-epidural labor analgesia. Techniques in Regional Anesthesia and Pain Management 2003; 7: 181-88

Responsible Party: Cynthia Wong, Professor of Anesthesiology, Northwestern University
ClinicalTrials.gov Identifier: NCT00418015     History of Changes
Other Study ID Numbers: 0524-025
Study First Received: December 31, 2006
Results First Received: February 15, 2011
Last Updated: March 17, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Northwestern University:
µ-opioid receptor
neuraxial labor analgesia
pharmacogenetics

Additional relevant MeSH terms:
Labor Pain
Pain
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms

ClinicalTrials.gov processed this record on September 18, 2014