Effect of Mu-opioid Receptor Genetics on 3 Doses of Spinal Morphine for Postoperative Analgesia After Cesarean Section
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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 |
- 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
- 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 |
Inclusion Criteria:
- healthy women undergoing elective cesarean
Exclusion Criteria:
- cardiovascular disease
- analgesic medications
- complications of pregnancy
Contacts and Locations| Contact: Richard M Smiley, MD, PhD | 212-305-5006 | rms7@columbia.edu |
| 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 | |
| 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 Anesthetics Morphine Analgesics, Opioid Central Nervous System Depressants |
Physiological Effects of Drugs Pharmacologic Actions Central Nervous System Agents Therapeutic Uses Analgesics Sensory System Agents Peripheral Nervous System Agents Narcotics |
ClinicalTrials.gov processed this record on May 22, 2013