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Mu-Opioid Receptor Genetic Polymorphism and Intrathecal Analgesia

This study is currently recruiting participants.
Verified by Northwestern University, December 2006

Sponsored by: Northwestern University
Information provided by: Northwestern University
ClinicalTrials.gov Identifier: NCT00418015
  Purpose

Pharmocogenetics 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 µ-opioid receptor (OPRM1). The mutated protein, N40D, appears to increase the binding affinity and potency of β-endorphin approximately 3-fold. Individuals carrying the variant receptor gene (A118G) may show differences in some of the functions mediated by β-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 µg was 89 ± 43 min. The ED50 of intrathecal fentanyl for labor analgesia varies between 14 µg to 18.2 µg. 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 µ-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
Labour
Post-Cesarean Delivery
Procedure: Blood Draw

ChemIDplus related topics:   Fentanyl Citrate    Fentanyl   

U.S. FDA Resources

Study Type:   Observational
Study Design:   Screening, Cross-Sectional, Random Sample, Prospective Study
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

Further study details as provided by Northwestern University:

Estimated Enrollment:   265
Study Start Date:   October 2005

Show detailed description  Show Detailed Description

  Eligibility
Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes

Criteria

Inclusion Criteria:Study1) Nulliparous women in spontaneous labor or with spontaneous rupture of membranes, term pregnancy (≥ 37 weeks gestation), vertex presentation, healthy, ASA PS 1-2, who plan neuraxial labor analgesia. Study 2) Nulliparous women undergoing elective primary Cesarean delivery (e.g., for breech presentation, macrosomia), term pregnancy (≥ 37 weeks gestation), healthy, ASA PS 1-2, planned spinal anesthesia.

Exclusion Criteria:1) 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, Cesarean delivery. 2) 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.

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  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00418015

Contacts
Contact: Cynthia Wong, M.D.     312-926-1772     c-wong2@northwestern.edu    
Contact: Robert McCarthy, PharmD.     312-926-9015     r-mccarthy@northwestern.edu    

Locations
United States, Illinois
Northwestern University     Recruiting
      Chicago, Illinois, United States, 60611
      Principal Investigator: Cynthia A Wong, M.D.            

Sponsors and Collaborators
Northwestern University

Investigators
Principal Investigator:     Cynthia A Wong, M.D.     Northwestern University    
  More Information


Publications:
Palmer SN, Giesecke NM, Body SC, Shernan SK, Fox AA, Collard CD. Pharmacogenetics of anesthetic and analgesic agents. Anesthesiology. 2005 Mar;102(3):663-71. Review.
 
Befort K, Filliol D, Decaillot FM, Gaveriaux-Ruff C, Hoehe MR, Kieffer BL. A single nucleotide polymorphic mutation in the human mu-opioid receptor severely impairs receptor signaling. J Biol Chem. 2001 Feb 2;276(5):3130-7. Epub 2000 Nov 6.
 
Bond C, LaForge KS, Tian M, Melia D, Zhang S, Borg L, Gong J, Schluger J, Strong JA, Leal SM, Tischfield JA, Kreek MJ, Yu L. Single-nucleotide polymorphism in the human mu opioid receptor gene alters beta-endorphin binding and activity: possible implications for opiate addiction. Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9608-13.
 
Grosch S, Niederberger E, Lotsch J, Skarke C, Geisslinger G. A rapid screening method for a single nucleotide polymorphism (SNP) in the human MOR gene. Br J Clin Pharmacol. 2001 Dec;52(6):711-4.
 
Hollt V. A polymorphism (A118G) in the mu-opioid receptor gene affects the response to morphine-6-glucuronide in humans. Pharmacogenetics. 2002 Jan;12(1):1-2. No abstract available.
 
Lotsch J, Skarke C, Grosch S, Darimont J, Schmidt H, Geisslinger G. The polymorphism A118G of the human mu-opioid receptor gene decreases the pupil constrictory effect of morphine-6-glucuronide but not that of morphine. Pharmacogenetics. 2002 Jan;12(1):3-9.
 
LaForge KS, Shick V, Spangler R, Proudnikov D, Yuferov V, Lysov Y, Mirzabekov A, Kreek MJ. Detection of single nucleotide polymorphisms of the human mu opioid receptor gene by hybridization or single nucleotide extension on custom oligonucleotide gelpad microchips: potential in studies of addiction. Am J Med Genet. 2000 Oct 9;96(5):604-15.
 
Wang D, Quillan JM, Winans K, Lucas JL, Sadee W. Single nucleotide polymorphisms in the human mu opioid receptor gene alter basal G protein coupling and calmodulin binding. J Biol Chem. 2001 Sep 14;276(37):34624-30. Epub 2001 Jul 16.
 
Town T, Abdullah L, Crawford F, Schinka J, Ordorica PI, Francis E, Hughes P, Duara R, Mullan M. Association of a functional mu-opioid receptor allele (+118A) with alcohol dependency. Am J Med Genet. 1999 Oct 15;88(5):458-61.
 
Shi J, Hui L, Xu Y, Wang F, Huang W, Hu G. Sequence variations in the mu-opioid receptor gene (OPRM1) associated with human addiction to heroin. Hum Mutat. 2002 Apr;19(4):459-60.
 
Schinka JA, Town T, Abdullah L, Crawford FC, Ordorica PI, Francis E, Hughes P, Graves AB, Mortimer JA, Mullan M. A functional polymorphism within the mu-opioid receptor gene and risk for abuse of alcohol and other substances. Mol Psychiatry. 2002;7(2):224-8.
 
Sander T, Gscheidel N, Wendel B, Samochowiec J, Smolka M, Rommelspacher H, Schmidt LG, Hoehe MR. Human mu-opioid receptor variation and alcohol dependence. Alcohol Clin Exp Res. 1998 Dec;22(9):2108-10.
 
Palmer CM, Cork RC, Hays R, Van Maren G, Alves D. The dose-response relation of intrathecal fentanyl for labor analgesia. Anesthesiology. 1998 Feb;88(2):355-61.
 
Nelson KE, Rauch T, Terebuh V, D'Angelo R. A comparison of intrathecal fentanyl and sufentanil for labor analgesia. Anesthesiology. 2002 May;96(5):1070-3.
 
Clarke VT, Smiley RM, Finster M. Uterine hyperactivity after intrathecal injection of fentanyl for analgesia during labor: a cause of fetal bradycardia? Anesthesiology. 1994 Oct;81(4):1083. No abstract available.
 
Landau R, Cahana A, Smiley RM, Antonarakis SE, Blouin JL. Genetic variability of mu-opioid receptor in an obstetric population. Anesthesiology. 2004 Apr;100(4):1030-3. No abstract available.
 
Palmer CM, Emerson S, Volgoropolous D, Alves D. Dose-response relationship of intrathecal morphine for postcesarean analgesia. Anesthesiology. 1999 Feb;90(2):437-44. Erratum in: Anesthesiology 1999 Apr;90(4):1241.
 
Ronaghi M, Uhlen M, Nyren P. A sequencing method based on real-time pyrophosphate. Science. 1998 Jul 17;281(5375):363, 365. No abstract available.
 
Wasson J, Skolnick G, Love-Gregory L, Permutt MA. Assessing allele frequencies of single nucleotide polymorphisms in DNA pools by pyrosequencing technology. Biotechniques. 2002 May;32(5):1144-6, 1148, 1150 passim.
 
Neve B, Froguel P, Corset L, Vaillant E, Vatin V, Boutin P. Rapid SNP allele frequency determination in genomic DNA pools by pyrosequencing. Biotechniques. 2002 May;32(5):1138-42.
 

Study ID Numbers:   0524-025
First Received:   December 31, 2006
Last Updated:   December 31, 2006
ClinicalTrials.gov Identifier:   NCT00418015
Health Authority:   United States: Institutional Review Board

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

Study placed in the following topic categories:
Morphine
Fentanyl

ClinicalTrials.gov processed this record on October 15, 2008




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