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

NCT01465191 | Completed Phase 4 Results

• 1 other identifier: AAAI2804
• Study Type: interventional
• Target: 169
• Locations: 1 country
• Sites: 2

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.

Conditions

Postoperative Pain

Keywords

cesarean; postoperative; morphine; genetics; opioid

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (13)

• Visual Analog Scale (VAS) Pain at 6 Hours

  6 hours post-operatively

• Visual Analog Scale (VAS) Pain at 12 Hours

  12 hours post-operatively

• Visual Analog Scale (VAS) Pain at 18 Hours

  18 hours post-operatively

• Visual Analog Scale (VAS) Pain at 24 Hours

  24 hours post-operatively

• Visual Analog Scale- Nausea/Vomiting at 6 Hours

  6 hours post-operatively

Study Arms (3)

50 micrograms (mcg) spinal morphine

EXPERIMENTAL

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

Drug: Morphine

100 micrograms spinal morphine

EXPERIMENTAL

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

Drug: Morphine

150 micrograms spinal morphine

EXPERIMENTAL

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

Drug: Morphine

Interventions

Morphine DRUG

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

100 micrograms spinal morphine; 150 micrograms spinal morphine; 50 micrograms (mcg) spinal morphine

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• healthy women undergoing elective cesarean

You may not qualify if:

• cardiovascular disease
• analgesic medications
• complications of pregnancy

Sponsors & Collaborators

• Columbia University: lead

Study Sites (2)

George Washington University Medical Center

Washington D.C., District of Columbia, 20037, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Morphine

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Richard Smiley, MD
• Organization: Columbia University

rms7@cumc.columbia.edu

212-342-2742

Study Officials

• Richard M Smiley, MD, PhD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professr of Clinical Anesthesiology

Study Record Dates

• First Submitted: November 2, 2011
• First Posted: November 4, 2011
• Study Start: November 1, 2011
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: December 10, 2020
• Results First Posted: December 10, 2020

Record last verified: 2020-11

Locations

US (2)