Mu-Opioid Receptor Genetic Polymorphism and Intrathecal Analgesia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00418015
Recruitment Status : Completed
First Posted : January 4, 2007
Results First Posted : April 18, 2011
Last Update Posted : April 14, 2014
Information provided by (Responsible Party):
Cynthia Wong, Northwestern University

Brief Summary:
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 or disease Intervention/treatment
Labor Pain Post-cesarean Delivery Procedure: Blood Draw

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Study Type : Observational
Actual Enrollment : 293 participants
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
Study Start Date : October 2005
Actual Primary Completion Date : May 2007
Actual Study Completion Date : June 2007

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cesarean Section
U.S. FDA Resources

Group/Cohort Intervention/treatment
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

Primary Outcome Measures :
  1. Duration of Intrathecal Fentanyl Analgesia [ Time Frame: Time (0-1440 minutes) to first analgesia request ]
    Time from intrathecal drug administration to request for analgesia either in laboring women of after cesarean delivery

  2. Duration of Intrathecal Analgesia Following Cesarean Delivery [ Time Frame: 0 to 72 hours following cesarean delivery ]
    Time until request for supplemental analgesia following intrathecal morphine/fentanyl for cesarean delivery

  3. Visual Analog Pain Scale (0 to 100) at Analgesia Request Following Intrathecal Intervention [ Time Frame: VAS at analgesia request ]
    Visual analog pain scale (0 to 100) at 1st request for supplemental analgesia

Secondary Outcome Measures :
  1. Severity of Pruritus Following Fentanyl [ Time Frame: Labor analgesia ]
    Severity of pruritus during labor analgesia

  2. Subjects With Pruritus at 24 Hours Post Morphine [ Time Frame: 24 hours post cesarean delivery ]
    Subjects reporting pruritus in the first 24 hours post cesarean delivery

Biospecimen Retention:   Samples With DNA
Blood Samples

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Pregnant women

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00418015

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

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 Identifier: NCT00418015     History of Changes
Other Study ID Numbers: 0524-025
First Posted: January 4, 2007    Key Record Dates
Results First Posted: April 18, 2011
Last Update Posted: April 14, 2014
Last Verified: March 2014

Keywords provided by Cynthia Wong, Northwestern University:
µ-opioid receptor
neuraxial labor analgesia

Additional relevant MeSH terms:
Labor Pain
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Analgesics, Opioid
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Adjuvants, Anesthesia
Anesthetics, Intravenous
Anesthetics, General