Effect of Mu-opioid Receptor Genetics on 3 Doses of Spinal Morphine for Postoperative Analgesia After Cesarean Section

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2012 by Columbia University.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Richard M. Smiley, Columbia University
ClinicalTrials.gov Identifier:
NCT01465191
First received: November 2, 2011
Last updated: April 1, 2012
Last verified: February 2012
  Purpose

HYPOTHESIS: The response to a given dose of morphine given via a spinal anesthetic for cesarean section will be affected by the genetics of the woman's mu-opioid receptor

Most women undergoing elective cesarean section (CS) receive spinal anesthesia, and most receive a dose of preservative free morphine with the spinal anesthetic. Spinally-administered morphine provides 16-24 hours of high quality pain relief. The dose administered is usually 75-200 micrograms, but surprisingly few dose-response studies exist.

The mu-opioid receptor (OPRM1 gene)is the site of action of endogenous opioid peptides and opioid analgesic drugs like morphine. There is a common genetic variant of this receptor at the 40th amino acid of the protein, with asparagine and asparate being present in different people. The less common variant (aspartate), present in 25-30% of the overall American population (higher in Asian populations, lower in Blacks) at codon 40 that has been shown in many studies to affect opioid analgesia.

This will be a randomized, blinded study of 3 doses of spinal morphine (50, 100, 150 micrograms) given to women undergoing elective cesarean section at term pregnancy. 300 women will be studied (100 per dose). Blood will be obtained for genotyping of OPRM1 and other genes that may affect pain and analgesic responses. The primary outcome will be the amount of intravenous morphine patients self-administer in the 24 hours postsurgery.

The primary outcome (use of intravenous morphine) will be analyzed by dose, and within each dose group by genotype of OPRM1. Secondary outcomes will include pain scores every 6 hours, satisfaction with analgesia, side effects (itching, nausea/vomiting) by dose and genotype.


Condition Intervention Phase
Postoperative Pain
Drug: Morphine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of OPRM1 Genotype on the Dose Response to Spinal Morphine for Post-Cesarean Analgesia

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Milligrams of intravenous morphine used by patient in first 24 hours postoperatively [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    IV morphine use by patient-controlled analgesia will be assessed every 6 hours for 24 hours postop


Secondary Outcome Measures:
  • Pain scores at 6, 12, 18, and 24 hours [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    numerical pain scores at 6, 12, 18, 24 hours

  • nausea [ Time Frame: 6,12, 18, 24 hours postop ] [ Designated as safety issue: No ]
  • itching [ Time Frame: 6, 12, 18, 24 hours postop ] [ Designated as safety issue: No ]
  • patient satisfaction with analgesia [ Time Frame: 24 hours postop ] [ Designated as safety issue: No ]

Estimated Enrollment: 600
Study Start Date: November 2011
Estimated Study Completion Date: November 2013
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 50 micrograms spinal morphine
100 subjects will receive 50 mcg morphine in their spinal anesthetic for cesarean section
Drug: Morphine
Morphine will be given via spinal injection at doses of 50, 100, 150 micrograms as part of a spinal anesthetic for cesarean section
Experimental: 100 mcg
100 subjects will receive 100 mcg morphine in their spinal anesthetic for cesarean section
Drug: Morphine
Morphine will be given via spinal injection at doses of 50, 100, 150 micrograms as part of a spinal anesthetic for cesarean section
Experimental: 150 mcg
100 subjects will receive 150 mcg morphine in their spinal anesthetic for cesarean section
Drug: Morphine
Morphine will be given via spinal injection at doses of 50, 100, 150 micrograms as part of a spinal anesthetic for cesarean section

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • healthy women undergoing elective cesarean

Exclusion Criteria:

  • cardiovascular disease
  • analgesic medications
  • complications of pregnancy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01465191

Contacts
Contact: Richard M Smiley, MD, PhD 212-305-5006 rms7@columbia.edu

Locations
United States, District of Columbia
George Washington University Medical Center Not yet recruiting
Washington, District of Columbia, United States, 20037
Contact: Jeff Berger, MD    202-715-5296    jberger@mfa.gwu.edu   
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Principal Investigator: Richard M Smiley, MD, PhD         
Sponsors and Collaborators
Columbia University
Investigators
Principal Investigator: Richard M Smiley, MD, PhD Columbia University
  More Information

No publications provided

Responsible Party: Richard M. Smiley, Professr of Clinical Anesthesiology, Columbia University
ClinicalTrials.gov Identifier: NCT01465191     History of Changes
Other Study ID Numbers: AAAI2804
Study First Received: November 2, 2011
Last Updated: April 1, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Columbia University:
cesarean
postoperative
morphine
genetics
opioid

Additional relevant MeSH terms:
Pain, Postoperative
Postoperative Complications
Pathologic Processes
Pain
Signs and Symptoms
Morphine
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 19, 2014