Postoperative PainPhase 4NCT01465191
Effect of Mu-opioid Receptor Genetics on 3 Doses of Spinal Morphine for Postoperative Analgesia After Cesarean Section
A Phase 4 study testing Morphine in people with Postoperative Pain, run by Columbia University at 2 sites in United States.
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… Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Postoperative Pain
- What is being tested?
- Morphine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 169 participants
- Where
- 2 sitesUnited States
- Study dates
- Nov 2011to May 2014
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- healthy women undergoing elective cesarean
Who cannot join
- cardiovascular disease
- analgesic medications
- complications of pregnancy
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Columbia University Medical Center
New York, New York, 10032
George Washington University Medical Center
Washington D.C., District of Columbia, 20037
About this study
Official title: Effect of OPRM1 Genotype on the Dose Response to Spinal Morphine for Post-Cesarean Analgesia
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.
Read more
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
- Being tested
- Morphine
- Keywords
- cesarean, postoperative, morphine, genetics, opioid
- Medical subject headings
- Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MorphineDrug
Morphine will be given via spinal injection at doses of 50, 100, 150 micrograms as part of a spinal anesthetic for cesarean section
| Study group | Role | What they receive |
|---|---|---|
| 50 micrograms (mcg) spinal morphine | Experimental | Subjects will receive 50 mcg morphine in their spinal anesthetic for cesarean section Receives: Drug: Morphine |
| 100 micrograms spinal morphine | Experimental | Subjects will receive 100 mcg morphine in their spinal anesthetic for cesarean section Receives: Drug: Morphine |
| 150 micrograms spinal morphine | Experimental | Subjects will receive 150 mcg morphine in their spinal anesthetic for cesarean section Receives: Drug: Morphine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 hours
Secondary outcomes (13)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 24 hours postoperatively
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2011 (estimated)
- Study startNov 2011
- Primary completionMay 2014
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Postoperative PainStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 169 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Richard M. Smiley, Columbia University
- Investigators
- Richard M Smiley, MD, PhD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01465191
- Sponsor's protocol ID
- AAAI2804
- Status last verified
- Nov 2020
- First submitted
- 2 Nov 2011
- Last updated
- 10 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of OPRM1 Genotype on the Dose Response to Spinal Morphine for Post-Cesarean Analgesia
- ClinicalTrials.gov ID
- NCT01465191
- Acronym / sponsor ID
- AAAI2804
- Conditions
- Postoperative Pain
- Keywords
- cesarean, postoperative, morphine, genetics, opioid
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 169 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Study start
- Nov 2011
- Primary completion
- May 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 4 Nov 2011 (estimated)
- Results
- Posted 10 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 50 micrograms (mcg) spinal morphine | Experimental | Drug: MorphineSubjects will receive 50 mcg morphine in their spinal anesthetic for cesarean section |
| 100 micrograms spinal morphine | Experimental | Drug: MorphineSubjects will receive 100 mcg morphine in their spinal anesthetic for cesarean section |
| 150 micrograms spinal morphine | Experimental | Drug: MorphineSubjects will receive 150 mcg morphine in their spinal anesthetic for cesarean section |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- healthy women undergoing elective cesarean
Key exclusion criteria (3 listed)
- cardiovascular disease
- analgesic medications
- complications of pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MorphineMorphine will be given via spinal injection at doses of 50, 100, 150 micrograms as part of a spinal anesthetic for cesarean section | Drug | 100 micrograms spinal morphine, 150 micrograms spinal morphine, 50 micrograms (mcg) spinal morphine |
Primary outcome
Milligrams of Intravenous Morphine Used by Participant in First 24 Hours Postoperatively
Time frame: 24 hours
IV morphine use in milligrams, by participant-controlled analgesia will be assessed every 6 hours for 24 hours postoperatively.
13 secondary outcomes
Visual Analog Scale (VAS) Pain at 6 Hours
Time frame: 6 hours post-operatively
Visual Analog Scale (VAS) Pain at 12 Hours
Time frame: 12 hours post-operatively
Visual Analog Scale (VAS) Pain at 18 Hours
Time frame: 18 hours post-operatively
Visual Analog Scale (VAS) Pain at 24 Hours
Time frame: 24 hours post-operatively
Visual Analog Scale- Nausea/Vomiting at 6 Hours
Time frame: 6 hours post-operatively
Visual Analog Scale- Nausea/Vomiting at 12 Hours
Time frame: 12 hours post-operatively
Visual Analog Scale- Nausea/Vomiting at 18 Hours
Time frame: 18 hours post-operatively
Visual Analog Scale- Nausea/Vomiting at 24 Hours
Time frame: 24 hours post-operatively
Visual Analog Scale Pruritus (Itching) at 6 Hours
Time frame: 6 hours post-operatively
Visual Analog Scale Pruritus (Itching) at 12 Hours
Time frame: 12 hours post-operatively
Visual Analog Scale Pruritus (Itching) at 18 Hours
Time frame: 18 hours post-operatively
Visual Analog Scale Pruritus (Itching) at 24 Hours
Time frame: 24 hours post-operatively
Visual Analog Patient Satisfaction With Analgesia at 24 Hours
Time frame: 24 hours postoperatively
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Postoperative Pain
RecruitingPhase 4
ESP Blocks for Posterior Spinal Fusion
Postoperative Pain
Recruiting
Effect of Cryotherapeutic and Nanotherapeutic Sodium Hypochlorite on Post-Operative Endodontic Pain.
Symptomatic Irreversible Pulpitis, Symptomatic Apical Periodontitis
RecruitingPhase 2
REctus Sheath Trial
Acute Pain, Postoperative Pain, Acute
Not yet recruiting
Effect of Pectoral Nerve Block (PECS) Using Magnesium Sulfate Added to Dexamethasone on Quality of Recovery and Chronic Post-Mastectomy Pain
Breast Cancer, Postoperative Pain
Active, not recruitingPhase 4
Effect of Dexmedetomidine on Postoperative Pain in Spinal Anesthesia for Cesarean Section at Assuit University Hospital
Cesarean Section
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard M Smiley, MD, PhD principal investigator
Columbia University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Morphine in people with Postoperative Pain, run by Columbia University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Milligrams of Intravenous Morphine Used by Participant in First 24 Hours Postoperatively (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Dec 2020.