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

Phase 4
Completed
Conditions
Postoperative Pain
Interventions
Registration Number
NCT01465191
Lead Sponsor
Columbia University
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
169
Inclusion Criteria
  • healthy women undergoing elective cesarean
Exclusion Criteria
  • cardiovascular disease
  • analgesic medications
  • complications of pregnancy

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
50 micrograms (mcg) spinal morphineMorphineSubjects will receive 50 mcg morphine in their spinal anesthetic for cesarean section
100 micrograms spinal morphineMorphineSubjects will receive 100 mcg morphine in their spinal anesthetic for cesarean section
150 micrograms spinal morphineMorphineSubjects will receive 150 mcg morphine in their spinal anesthetic for cesarean section
Primary Outcome Measures
NameTimeMethod
Milligrams of Intravenous Morphine Used by Participant in First 24 Hours Postoperatively24 hours

IV morphine use in milligrams, by participant-controlled analgesia will be assessed every 6 hours for 24 hours postoperatively.

Secondary Outcome Measures
NameTimeMethod
Visual Analog Scale (VAS) Pain at 6 Hours6 hours post-operatively

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.

Visual Analog Scale (VAS) Pain at 12 Hours12 hours post-operatively

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.

Visual Analog Scale (VAS) Pain at 18 Hours18 hours post-operatively

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.

Visual Analog Scale (VAS) Pain at 24 Hours24 hours post-operatively

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.

Visual Analog Scale- Nausea/Vomiting at 6 Hours6 hours post-operatively

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).

Visual Analog Scale- Nausea/Vomiting at 12 Hours12 hours post-operatively

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).

Visual Analog Scale- Nausea/Vomiting at 18 Hours18 hours post-operatively

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).

Visual Analog Scale- Nausea/Vomiting at 24 Hours24 hours post-operatively

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).

Visual Analog Scale Pruritus (Itching) at 6 Hours6 hours post-operatively

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).

Visual Analog Scale Pruritus (Itching) at 12 Hours12 hours post-operatively

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).

Visual Analog Scale Pruritus (Itching) at 18 Hours18 hours post-operatively

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).

Visual Analog Scale Pruritus (Itching) at 24 Hours24 hours post-operatively

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).

Visual Analog Patient Satisfaction With Analgesia at 24 Hours24 hours postoperatively

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).

Trial Locations

Locations (2)

Columbia University Medical Center

🇺🇸

New York, New York, United States

George Washington University Medical Center

🇺🇸

Washington, District of Columbia, United States

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