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

Postoperative Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01465191
• Other study ID #: AAAI2804
• Status: Completed
• Phase: Phase 4
• Start date: November 2011
• Est. completion date: May 2014

Study information

• Verified date: November 2020
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 169
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• healthy women undergoing elective cesarean

Exclusion Criteria:

• cardiovascular disease

• analgesic medications

• complications of pregnancy

Related Conditions & MeSH terms

• Pain, Postoperative
• Postoperative Pain

Intervention

Drug:
• Morphine
Morphine will be given via spinal injection at doses of 50, 100, 150 micrograms as part of a spinal anesthetic for cesarean section

Locations

Country	Name	City	State
United States	Columbia University Medical Center	New York	New York
United States	George Washington University Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Columbia University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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