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

Study Overview
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Brief Summary
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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.

Official Title
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Effect of OPRM1 Genotype on the Dose Response to Spinal Morphine for Post-Cesarean Analgesia

Conditions
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Postoperative Pain

Intervention / Treatment
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* Drug: Morphine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy women undergoing elective cesarean Exclusion Criteria: cardiovascular disease analgesic medications complications of pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 50 micrograms (mcg) spinal morphine<br>Subjects will receive 50 mcg morphine in their spinal anesthetic for cesarean section | Drug: Morphine<br>* Morphine will be given via spinal injection at doses of 50, 100, 150 micrograms as part of a spinal anesthetic for cesarean section<br>|
| Experimental: 100 micrograms spinal morphine<br>Subjects will receive 100 mcg morphine in their spinal anesthetic for cesarean section | Drug: Morphine<br>* Morphine will be given via spinal injection at doses of 50, 100, 150 micrograms as part of a spinal anesthetic for cesarean section<br>|
| Experimental: 150 micrograms spinal morphine<br>Subjects will receive 150 mcg morphine in their spinal anesthetic for cesarean section | Drug: Morphine<br>* Morphine will be given via spinal injection at doses of 50, 100, 150 micrograms as part of a spinal anesthetic for cesarean section<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Milligrams of Intravenous Morphine Used by Participant in First 24 Hours Postoperatively | IV morphine use in milligrams, by participant-controlled analgesia will be assessed every 6 hours for 24 hours postoperatively. | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analog Scale (VAS) Pain at 6 Hours | Visual analog pain scale measures pain on a 100 millimeter (mm) scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst pain imaginable (100mm). Pain measured at rest and with movement. | 6 hours post-operatively | 
| Visual Analog Scale (VAS) Pain at 12 Hours | Visual analog pain scale measures pain on a 100 millimeter (mm) scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst pain imaginable (100mm). Pain measured at rest and with movement. | 12 hours post-operatively | 
| Visual Analog Scale (VAS) Pain at 18 Hours | Visual analog pain scale measures pain on a 100 millimeter (mm) scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst pain imaginable (100mm). Pain measured at rest and with movement. | 18 hours post-operatively | 
| Visual Analog Scale (VAS) Pain at 24 Hours | Visual analog pain scale measures pain on a 100 millimeter (mm) scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst pain imaginable (100mm). Pain measured at rest and with movement. | 24 hours post-operatively | 
| Visual Analog Scale- Nausea/Vomiting at 6 Hours | Visual analog nausea/vomiting scale measures nausea and vomiting on a 100mm scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst Nausea/Vomiting Imaginable (100mm). | 6 hours post-operatively | 
| Visual Analog Scale- Nausea/Vomiting at 12 Hours | Visual analog nausea/vomiting scale measures nausea and vomiting on a 100mm scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst Nausea/Vomiting Imaginable (100mm). | 12 hours post-operatively | 
| Visual Analog Scale- Nausea/Vomiting at 18 Hours | Visual analog nausea/vomiting scale measures nausea and vomiting on a 100mm scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst Nausea/Vomiting Imaginable (100mm). | 18 hours post-operatively | 
| Visual Analog Scale- Nausea/Vomiting at 24 Hours | Visual analog nausea/vomiting scale measures nausea and vomiting on a 100mm scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst Nausea/Vomiting Imaginable (100mm). | 24 hours post-operatively | 
| Visual Analog Scale Pruritus (Itching) at 6 Hours | Visual analog pruritus scale measures itching on a 100mm scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst Itching Imaginable (100mm). | 6 hours post-operatively | 
| Visual Analog Scale Pruritus (Itching) at 12 Hours | Visual analog pruritus scale measures itching on a 100mm scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst Itching Imaginable (100mm). | 12 hours post-operatively | 
| Visual Analog Scale Pruritus (Itching) at 18 Hours | Visual analog pruritus scale measures itching on a 100mm scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst Itching Imaginable (100mm). | 18 hours post-operatively | 
| Visual Analog Scale Pruritus (Itching) at 24 Hours | Visual analog pruritus scale measures itching on a 100mm scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst Itching Imaginable (100mm). | 24 hours post-operatively | 
| Visual Analog Patient Satisfaction With Analgesia at 24 Hours | Visual analog patient satisfaction scale measures satisfaction with analgesia on a 100mm scale. Participants make a mark on the scale with one end labeled Completely Dissatisfied (0mm) and the other labeled Completely Satisfied (100mm). | 24 hours postoperatively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cesarean, postoperative, morphine, genetics, opioid