Clinical trial NCT01465191: Effect of Mu-opioid Receptor Genetics on 3 Doses of Spinal Morphine for Postoperative Analgesia After Cesarean Section
Official title: Effect of OPRM1 Genotype on the Dose Response to Spinal Morphine for Post-Cesarean Analgesia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Postoperative Pain
Keywords: cesarean
postoperative
morphine
genetics
opioid
Lead sponsor: Columbia University
Sponsor class: OTHER
First posted: 2011-11-04
Enrollment: 169
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* healthy women undergoing elective cesarean

Exclusion Criteria:

* cardiovascular disease
* analgesic medications
* complications of pregnancy

Primary outcomes:
measure: Milligrams of Intravenous Morphine Used by Participant in First 24 Hours Postoperatively
timeFrame: 24 hours
Secondary outcomes:
measure: Visual Analog Scale (VAS) Pain at 6 Hours
timeFrame: 6 hours post-operatively
measure: Visual Analog Scale (VAS) Pain at 12 Hours
timeFrame: 12 hours post-operatively
measure: Visual Analog Scale (VAS) Pain at 18 Hours
timeFrame: 18 hours post-operatively
measure: Visual Analog Scale (VAS) Pain at 24 Hours
timeFrame: 24 hours post-operatively
measure: Visual Analog Scale- Nausea/Vomiting at 6 Hours
timeFrame: 6 hours post-operatively
measure: Visual Analog Scale- Nausea/Vomiting at 12 Hours
timeFrame: 12 hours post-operatively
measure: Visual Analog Scale- Nausea/Vomiting at 18 Hours
timeFrame: 18 hours post-operatively
measure: Visual Analog Scale- Nausea/Vomiting at 24 Hours
timeFrame: 24 hours post-operatively
measure: Visual Analog Scale Pruritus (Itching) at 6 Hours
timeFrame: 6 hours post-operatively
measure: Visual Analog Scale Pruritus (Itching) at 12 Hours
timeFrame: 12 hours post-operatively
measure: Visual Analog Scale Pruritus (Itching) at 18 Hours
timeFrame: 18 hours post-operatively
measure: Visual Analog Scale Pruritus (Itching) at 24 Hours
timeFrame: 24 hours post-operatively
measure: Visual Analog Patient Satisfaction With Analgesia at 24 Hours
timeFrame: 24 hours postoperatively
Other outcomes:
Locations:
city: Washington
country: United States
facility: George Washington University Medical Center
state: District of Columbia
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
Study officials:
affiliation: Columbia University
name: Richard M Smiley, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: