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Mu-Opioid Receptor Genetic Polymorphism and Intrathecal Analgesia
This study has been completed.
Study NCT00418015   Information provided by Northwestern University

First Received on December 31, 2006.   Last Updated on April 25, 2011   History of Changes
Results First Received: February 15, 2011  
Study Type: Observational
Study Design: Observational Model: Cohort;   Time Perspective: Prospective
Conditions: Labor Pain
Post-cesarean Delivery
Intervention: Procedure: Blood Draw

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Laboring subject recruited from 10/2005 to 9/2006 Post cesarean delivery subjects recruited from 10/2005 to 5/2007

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Subjects were excluded from the labor analgesia group if they had received an opioid analgesic before initiation of intrathecal analgesia or if they received neuraxial analgesia before 2cm of cervical dilation.

Reporting Groups
  Description
Labor Analgesia OPRM1 c304A Parturients that received spinal fentanyl 15 micrograms and epidural fentanyl labor analgesia who were homozygous for OPRM1 c304
Labor Analgesia OPRM1 c304A>G Parturients receiving spinal fentanyl 15 micrograms and epidural fentanyl labor analgesia that were heterozygous or homozygous for OPRM1 c304A>G
Cesarean Delivery OPRM1 c304A Cesarean delivery subjects receiving morphine 150 micrograms with spinal bupivacaine 12mg and fentanyl 15 micrograms that were homozygous for OPRM1 c304A
Cesarean Delivery OPRM1 c304A>G Cesarean delivery subjects receiving morphine 150 micrograms with spinal bupivacaine 12mg and fentanyl 15 micrograms that were heterozygous for OPRM1 c304A>G

Participant Flow:   Overall Study
    Labor Analgesia OPRM1 c304A     Labor Analgesia OPRM1 c304A>G     Cesarean Delivery OPRM1 c304A     Cesarean Delivery OPRM1 c304A>G  
STARTED     144     46     78     25  
COMPLETED     144     46     78     25  
NOT COMPLETED     0     0     0     0  



  Baseline Characteristics
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Reporting Groups
  Description
Labor Analgesia OPRM1 c304A Parturients that received spinal fentanyl 15 micrograms and epidural fentanyl labor analgesia who were homozygous for OPRM1 c304
Labor Analgesia OPRM1 c304A>G Parturients receiving spinal fentanyl 15 micrograms and epidural fentanyl labor analgesia that were heterozygous or homozygous for OPRM1 c304A>G
Cesarean Delivery OPRM1 c304A Cesarean delivery subjects receiving morphine 150 micrograms with spinal bupivacaine 12mg and fentanyl 15 micrograms that were homozygous for OPRM1 c304A
Cesarean Delivery OPRM1 c304A>G Cesarean delivery subjects receiving morphine 150 micrograms with spinal bupivacaine 12mg and fentanyl 15 micrograms that were heterozygous for OPRM1 c304A>G

Baseline Measures
    Labor Analgesia OPRM1 c304A     Labor Analgesia OPRM1 c304A>G     Cesarean Delivery OPRM1 c304A     Cesarean Delivery OPRM1 c304A>G     Total  
Number of Participants  
[units: participants]
 		  144     46     78     25     293  
Age  
[units: participants]
 		         
<=18 years     0     0     0     0     0  
Between 18 and 65 years     144     46     78     25     293  
>=65 years     0     0     0     0     0  
Age  
[units: years]
Median ( Inter-Quartile Range ) 		  30  
  ( 28 to 34 )   		  32  
  ( 30 to 34 )   		  34  
  ( 31 to 37 )   		  32  
  ( 29 to 35 )   		  32  
  ( 28 to 34 )  
Gender  
[units: participants]
 		         
Female     144     46     78     25     293  
Male     0     0     0     0     0  
Region of Enrollment  
[units: participants]
 		         
United States     144     46     78     25     293  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Duration of Intrathecal Fentanyl Analgesia   [ Time Frame: Time (0-1440 minutes) to first analgesia request ]
  Show Outcome Measure 1

2.  Primary:   Duration of Intrathecal Analgesia Following Cesarean Delivery   [ Time Frame: 0 to 72 hours following cesarean delivery ]
  Show Outcome Measure 2

3.  Primary:   Visual Analog Pain Scale (0 to 100) at Analgesia Request Following Intrathecal Intervention   [ Time Frame: VAS at analgesia request ]
  Show Outcome Measure 3

4.  Secondary:   Severity of Pruritus Following Fentanyl   [ Time Frame: Labor analgesia ]
  Show Outcome Measure 4

5.  Secondary:   Subjects With Pruritus at 24 Hours Post Morphine   [ Time Frame: 24 hours post cesarean delivery ]
  Show Outcome Measure 5


  Serious Adverse Events
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  Other Adverse Events
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  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
A limitation to the finding of this study was the relatively low number of OPRM1 heterozygous subjects.  


Results Point of Contact:  
Name/Title: Dr. Robert J. McCarthy
Organization: Northwestern University Feinberg School of Medicine
phone: 3129269015
e-mail: r-mccarthy@northwestern.edu


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


Responsible Party: Cynthia A. Wong, M.D., 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: April 25, 2011
Health Authority: United States: Institutional Review Board





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