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

Columbia University

Status and phase: Completed; Phase 4

Conditions: Postoperative Pain

Treatments: Drug: Morphine

Study type: Interventional

Funder types: Other

Identifiers

NCT01465191

AAAI2804

Details and patient eligibility

About

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.

Enrollment: 169 patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• healthy women undergoing elective cesarean

Exclusion criteria

• cardiovascular disease
• analgesic medications
• complications of pregnancy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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169 participants in 3 patient groups

50 micrograms (mcg) spinal morphine

Experimental group

Description:

Subjects will receive 50 mcg morphine in their spinal anesthetic for cesarean section

Treatment:

Drug: Morphine

100 micrograms spinal morphine

Experimental group

Description:

Subjects will receive 100 mcg morphine in their spinal anesthetic for cesarean section

Treatment:

Drug: Morphine

150 micrograms spinal morphine

Experimental group

Description:

Subjects will receive 150 mcg morphine in their spinal anesthetic for cesarean section

Treatment:

Drug: Morphine