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

NCT ID: NCT01465191

Last Updated: 2020-12-10

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

169 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-11-30

Study Completion Date

2014-05-31

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.

Detailed Description

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Conditions

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Postoperative Pain

Keywords

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cesarean postoperative morphine genetics opioid

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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50 micrograms (mcg) spinal morphine

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

Group Type EXPERIMENTAL

Morphine

Intervention Type 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

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

Group Type EXPERIMENTAL

Morphine

Intervention Type DRUG

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

150 micrograms spinal morphine

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

Group Type EXPERIMENTAL

Morphine

Intervention Type DRUG

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

Interventions

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Morphine

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* healthy women undergoing elective cesarean

Exclusion Criteria

* cardiovascular disease
* analgesic medications
* complications of pregnancy
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Columbia University

OTHER

Sponsor Role lead

Responsible Party

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Richard M. Smiley

Professr of Clinical Anesthesiology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Richard M Smiley, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

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George Washington University Medical Center

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

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Countries

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United States

Other Identifiers

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AAAI2804

Identifier Type: -

Identifier Source: org_study_id