Post-operative PainCYP2D6NCT06723379
Genetics of Cytochrome CYP2D6 and Effects of Codeine and Tramadol on Postoperative Pain Management
An observational study of Post-operative Pain, run by Fraser Health at 1 site in Canada.
Trial summary
Codeine is one of the most commonly prescribed opioids in the world. The speed at which our liver metabolizes codeine into morphine depends on an important protein called cytochrome P450 2D6 (CYP2D6). Many people across the world have different CYP2D6 metabolizing speeds. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Post-operative Pain
- How many people
- 22 participants
- Where
- 1 siteCanada
- Study dates
- 25 Nov 2022to 1 Dec 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: For the pilot study, healthy patients (ASA 1 or 2) who are undergoing surgical procedures at Royal Columbian Hospital or Eagle Ridge Hospital with projected moderate postoperative pain will be selected. It is estimated that five patients will be approached to learn more about the study each week and 50-60% will consent to participate given the minimally invasive study procedures and the potential for participants to learn valuable personal pain medication metabolizing genetic status. Therefore, this study aims to enroll approximately ten patients per month up to a maximum of fifty total patients over a five-month span.
Who may be able to join
- Age 18-55 year and otherwise healthy (ASA 1 or 2)
- Undergoing an elective outpatient surgical procedure at Royal Columbian Hospital or Eagle Ridge Hospital with projected moderate post-operative pain
- Surgical procedure that requires general anaesthetic and post-operative pain management routinely managed with either codeine or tramadol by attending surgeon (i.e., ACL repair)
- Attending surgeon routinely prescribes either tramadol or codeine for post-operative pain management
Who cannot join
- Pre-existing chronic pain condition
- Any psychiatric diagnosis, such as depression or anxiety (Lautenbacher et al., 1994)
- History of substance abuse/dependence
- Multiple medical comorbidities (a single well-controlled medical comorbidity will not be a contraindication - i.e., controlled hypothyroidism)
- Allergy, sensitivity, or other contraindication to either codeine or tramadol
- Regional anesthetic (inclusive either of a major peripheral nerve block or neuraxial anesthetic) planned by attending anesthesiologist)
- Unable to provide informed consent
Trial locations and contacts
1 site in 1 country.
Canada1 site
Royal Columbian Hospital
New Westminster, British Columbia, V3L 3W7
About this study
Official title: A Genetic Survey of Cytochrome P450 2D6 Genotypes by Nanopore DNA Sequencing and Clinical Response to Codeine and Tramadol in Postoperative Pain Management
Codeine is one of the most commonly prescribed opioids in the world. The speed at which our liver metabolizes codeine into morphine depends on an important protein called cytochrome P450 2D6 (CYP2D6). Many people across the world have different CYP2D6 metabolizing speeds. Codeine provides inadequate pain management to those who have slow-metabolizing CYP2D6. In contrast, codeine can be life-threatening to those who have rapidly-metabolizing CYP2D6 because of the abruptly high dose of morphine. By analyzing specific genes, we are able to predict a patient's response to medication, thus drug type and dosing can be tailored according to their genetics. The purpose of this study is to observe if nanopore CYP2D6 DNA genetic sequencing can classify patients according to their CYP2D6 phenotype and thus predict their response to codeine and tramadol. The overall project is to determine the practicality of a genetic survey of CYP2D6 for healthy patients undergoing surgical procedures.
Read the detailed description
PURPOSE: The purpose of this study is to investigate if genetic variants of CYP2D6 are a predictive factor for postoperative pain management with conventional codeine and tramadol pain therapy. With CYP2D6 DNA analysis, we hope to be able to correlate a patients' genetics and their physiological response to conventional codeine and tramadol dosing.
RESEARCH QUESTION: Is CYP2D6 metabolizer status a predictive factor for the effectiveness of postoperative pain management with conventional pain therapy doses of codeine and tramadol?
HYPOTHESIS: Our hypothesis is that patients with known rapid metabolizing CYP2D6 variants will have higher incidences of opioid side effects with conventional opioid dosing. On the other hand, patients with known poor-metabolizing CYP2D6 variants will have inadequate pain management with conventional opioid dosing.
JUSTIFICATION: Understanding the relationship between CYP2D6 variants and conventional opioid dosing in a clinical setting will facilitate future studies that investigate personalized dosing in order to improve pain management and reduce risk of opioid side effects.
OBJECTIVES: The primary objective of this study is to determine the practicality of undertaking a medium-scale genetic survey of CYP2D6 for healthy patients undergoing surgical procedures. Secondary objectives include: investigate the feasibility of characterizing CYP2D6 genetic variants into one of four metabolizer groups, investigate if there is a distinguishable pattern between CYP2D6 metabolizer status and postoperative pain management quality with conventional pain therapy dosages such as codeine and tramadol, investigate if there is a distinguishable pattern between CYP2D6 metabolizer status and the presence of opioid side effects with conventional pain therapy dosages such as codeine and tramadol, to raise awareness of the clinical relevance of CYP2D6 variants on codeine and tramadol metabolism as well as the complications that arise from conventional, non-personalized pain management.
RESEARCH DESIGN: Prospective observational feasibility study of healthy elective surgical patients. Projected enrolment up to 50 participants. All participants receive standardized anesthetic with weight based dosing of opiates. Data collected will include: 2-3 ml blood sample taken prior to surgery under general anesthesia, DNA sequencing and genotype identification, chart review during post-operative care unit stay (PACU), and a survey administered by phone 24 after discharge from the PACU.
STATISTICAL ANALYSIS: Given the exploratory nature of this feasibility study and small convenience sample size, data will be summarized using descriptive statistics for most outcome variables. If possible, nonparametric statistical tests may be performed to look at associations between genetic variant and outcomes and differences between the groups.
- Conditions
- Post-operative Pain
- Medical subject headings
- Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Healthy surgical patients | Healthy surgical patients who are undergoing surgical procedures with projected moderate postoperative pain. |
What is being measured
The primary outcome is the main question the study is designed to answer.
CYP2D6 genotypes/phenotypes
CYP2D6 genotype determined by nanopore DNA sequencing which will be cross-referenced with published genotypes to determine CYP2D6 phenotype
Measured: 6 months
Secondary outcomes (7)
Total opiate consumption
Total opiate consumption (morphine milligram equivalents, continuous) observed immediately post-op, before tramadol or codeine administration, and 1 hour or later post tramadol/codeine administration
Measured: 6 months
Pain scores
Pain scores (0 - 10, ordinal) observed immediately post-op, before tramadol or codeine administration, and 1 hour or later post tramadol/codeine administration
Measured: 6 months
Sedation level
Sedation assessments (1 - 4, ordinal) observed immediately post-op, before tramadol or codeine administration, and 1 hour or later post tramadol/codeine administration
Measured: 6 months
Administration of anti-nausea medications
Administration of anti-nausea medications (Yes/No, dichotomous) observed immediately post-op, before tramadol or codeine administration, and 1 hour or later post tramadol/codeine administration
Measured: 6 months
Postoperative Day 1 current pain and worst pain since discharge
Current pain and worst pain since discharge (0 - 10, ordinal) at 24-hour post-op discharge telephone follow-up call
Measured: 6 months
Postoperative Day 1 Nausea and vomiting (Yes/No, dichotomous)
Nausea and vomiting (Yes/No, dichotomous) at 24-hour post-op discharge telephone follow-up call.
Measured: 6 months
Total opioids taken since discharge
Total opioids taken since discharge (morphine milligram equivalents, continuous) at 24-hour post-op discharge telephone follow-up call.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2024
- Study start25 Nov 2022
- Primary completion10 Jul 2024
- Study completion1 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post-operative PainStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fraser Health
- Sponsor type
- University, hospital or other
- Collaborators
- University of British Columbia
- Responsible party
- Principal investigator, Perseus Missirlis, Fraser Health
- Investigators
- Perseus Missirlis, MSc, MD, Principal investigator, Fraser Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06723379
- Sponsor's protocol ID
- 21-01422
- Acronym
- CYP2D6
- Status last verified
- Dec 2024
- First submitted
- 4 Dec 2024
- Last updated
- 9 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Genetic Survey of Cytochrome P450 2D6 Genotypes by Nanopore DNA Sequencing and Clinical Response to Codeine and Tramadol in Postoperative Pain Management
- ClinicalTrials.gov ID
- NCT06723379
- Acronym / sponsor ID
- CYP2D6 / 21-01422
- Conditions
- Post-operative Pain
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Fraser HealthUniversity, hospital or other
- Collaborators
- University of British Columbia
- Study start
- 25 Nov 2022 (actual)
- Primary completion
- 10 Jul 2024 (actual)
- Study completion
- 1 Dec 2024 (actual)
- First posted
- 9 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Codeine is one of the most commonly prescribed opioids in the world. The speed at which our liver metabolizes codeine into morphine depends on an important protein called cytochrome P450 2D6 (CYP2D6). Many people across the world have different CYP2D6 metabolizing speeds. Codeine provides inadequate pain management to those who have slow-metabolizing CYP2D6. In contrast, codeine can be life-threatening to those who have rapidly-metabolizing CYP2D6 because of the abruptly high dose of morphine. By analyzing specific genes, we are able to predict a patient's response to medication, thus drug type and dosing can be tailored according to their genetics. The purpose of this study is to observe if nanopore CYP2D6 DNA genetic sequencing can classify patients according to their CYP2D6 phenotype and thus predict their response to codeine and tramadol. The overall project is to determine the practicality of a genetic survey of CYP2D6 for healthy patients undergoing surgical procedures.
Detailed description
PURPOSE: The purpose of this study is to investigate if genetic variants of CYP2D6 are a predictive factor for postoperative pain management with conventional codeine and tramadol pain therapy. With CYP2D6 DNA analysis, we hope to be able to correlate a patients' genetics and their physiological response to conventional codeine and tramadol dosing.
RESEARCH QUESTION: Is CYP2D6 metabolizer status a predictive factor for the effectiveness of postoperative pain management with conventional pain therapy doses of codeine and tramadol?
HYPOTHESIS: Our hypothesis is that patients with known rapid metabolizing CYP2D6 variants will have higher incidences of opioid side effects with conventional opioid dosing. On the other hand, patients with known poor-metabolizing CYP2D6 variants will have inadequate pain management with conventional opioid dosing.
JUSTIFICATION: Understanding the relationship between CYP2D6 variants and conventional opioid dosing in a clinical setting will facilitate future studies that investigate personalized dosing in order to improve pain management and reduce risk of opioid side effects.
OBJECTIVES: The primary objective of this study is to determine the practicality of undertaking a medium-scale genetic survey of CYP2D6 for healthy patients undergoing surgical procedures. Secondary objectives include: investigate the feasibility of characterizing CYP2D6 genetic variants into one of four metabolizer groups, investigate if there is a distinguishable pattern between CYP2D6 metabolizer status and postoperative pain management quality with conventional pain therapy dosages such as codeine and tramadol, investigate if there is a distinguishable pattern between CYP2D6 metabolizer status and the presence of opioid side effects with conventional pain therapy dosages such as codeine and tramadol, to raise awareness of the clinical relevance of CYP2D6 variants on codeine and tramadol metabolism as well as the complications that arise from conventional, non-personalized pain management.
RESEARCH DESIGN: Prospective observational feasibility study of healthy elective surgical patients. Projected enrolment up to 50 participants. All participants receive standardized anesthetic with weight based dosing of opiates. Data collected will include: 2-3 ml blood sample taken prior to surgery under general anesthesia, DNA sequencing and genotype identification, chart review during post-operative care unit stay (PACU), and a survey administered by phone 24 after discharge from the PACU.
STATISTICAL ANALYSIS: Given the exploratory nature of this feasibility study and small convenience sample size, data will be summarized using descriptive statistics for most outcome variables. If possible, nonparametric statistical tests may be performed to look at associations between genetic variant and outcomes and differences between the groups.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Healthy surgical patients | – | –Healthy surgical patients who are undergoing surgical procedures with projected moderate postoperative pain. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- For the pilot study, healthy patients (ASA 1 or 2) who are undergoing surgical procedures at Royal Columbian Hospital or Eagle Ridge Hospital with projected moderate postoperative pain will be selected. It is estimated that five patients will be approached to learn more about the study each week and 50-60% will consent to participate given the minimally invasive study procedures and the potential for participants to learn valuable personal pain medication metabolizing genetic status. Therefore, this study aims to enroll approximately ten patients per month up to a maximum of fifty total patients over a five-month span.
Key inclusion criteria (4 listed)
- Age 18-55 year and otherwise healthy (ASA 1 or 2)
- Undergoing an elective outpatient surgical procedure at Royal Columbian Hospital or Eagle Ridge Hospital with projected moderate post-operative pain
- Surgical procedure that requires general anaesthetic and post-operative pain management routinely managed with either codeine or tramadol by attending surgeon (i.e., ACL repair)
- Attending surgeon routinely prescribes either tramadol or codeine for post-operative pain management
Key exclusion criteria (7 listed)
- Pre-existing chronic pain condition
- Any psychiatric diagnosis, such as depression or anxiety (Lautenbacher et al., 1994)
- History of substance abuse/dependence
- Multiple medical comorbidities (a single well-controlled medical comorbidity will not be a contraindication - i.e., controlled hypothyroidism)
- Allergy, sensitivity, or other contraindication to either codeine or tramadol
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
CYP2D6 genotypes/phenotypes
Time frame: 6 months
CYP2D6 genotype determined by nanopore DNA sequencing which will be cross-referenced with published genotypes to determine CYP2D6 phenotype
7 secondary outcomes
Total opiate consumption
Time frame: 6 months
Pain scores
Time frame: 6 months
Sedation level
Time frame: 6 months
Administration of anti-nausea medications
Time frame: 6 months
Postoperative Day 1 current pain and worst pain since discharge
Time frame: 6 months
Postoperative Day 1 Nausea and vomiting (Yes/No, dichotomous)
Time frame: 6 months
Total opioids taken since discharge
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2024.
- Individual participant dataSharing planned: No
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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.
Perseus Missirlis, MSc, MD principal investigator
Fraser Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Post-operative Pain, run by Fraser Health at 1 site in Canada.
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 4 inclusion and 7 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 9 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
CYP2D6 genotypes/phenotypes (time frame: 6 months). 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 9 Dec 2024.