Effect of Mu-opioid Receptor Genetics on 3 Doses of Spinal Morphine for Postoperative Analgesia After Cesarean Section
| Status: | Recruiting |
|---|---|
| Conditions: | Post-Surgical Pain |
| Therapuetic Areas: | Musculoskeletal |
| Healthy: | No |
| Age Range: | 18 - 45 |
| Updated: | 4/2/2016 |
| Start Date: | November 2011 |
| End Date: | November 2016 |
| Contact: | Richard M Smiley, MD, PhD |
| Email: | rms7@columbia.edu |
| Phone: | 212-305-5006 |
Effect of OPRM1 Genotype on the Dose Response to Spinal Morphine for Post-Cesarean Analgesia
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.
It is anticipated that there will be an interim data analysis at 150 evaluable subjects for
assessment of the dose response to morphine in the overall population; then a final analysis
at 300 subjects for the genetic effect assessment.
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.
It is anticipated that there will be an interim data analysis at 150 evaluable subjects for
assessment of the dose response to morphine in the overall population; then a final analysis
at 300 subjects for the genetic effect assessment.
Inclusion Criteria:
- healthy women undergoing elective cesarean
Exclusion Criteria:
- cardiovascular disease
- analgesic medications
- complications of pregnancy
We found this trial at
2
sites
Columbia University Medical Center Situated on a 20-acre campus in Northern Manhattan and accounting for...
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