Cytochrome P450 2D6 Ultra-rapid MetabolismNCT01050400
CYP2D6 Screening for Adverse Drug Reactions to Codeine in Breast Milk
An observational study of Cytochrome P450 2D6 Ultra-rapid Metabolism, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.
Trial summary
The purpose of this study is to determine if non-invasive salivary genetic screening of breastfeeding mothers taking codeine will allow for the successful identification of mother-infant pairs susceptible to adverse events and to prevent these adverse events by personalizing their medication to their genetics. Read more about this study
- Who is it for?
- Any age, women onlyHealthy volunteers can take part
- Conditions the study is for
- Cytochrome P450 2D6 Ultra-rapid Metabolism
- What is being tested?
- Cytochrome P450 2D6 (CYP2D6) genetic screening.
- How many people
- 330 participants
- Where
- 1 siteCanada
- Study dates
- 24 Feb 2009to 31 Dec 2012
- 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 Any age
- Women only
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Women undergoing elective caesarian section surgery and planning to breastfeed while concurrently taking codeine for post-partum pain relief within St. Joseph's Hospital in London and St. Michael's Hospital in Toronto.
Who may be able to join
- Women who:
- Have a pre-scheduled Caesarean section
- Provide DNA for CYP2D6 genetic analysis
- Breastfeed their infants
- Take codeine-containing medication during breastfeeding (retrospective screening group and non-CYP2D6 ultrarapid metabolizers in prospective screening group)
Who cannot join
- Mothers who do not provide consent prior to Caesarian section surgery
- Mothers who take other sedative medications besides codeine during breastfeeding (these include benzodiazepines, skeletal muscle relaxants, psychotropic agents).
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to determine if non-invasive salivary genetic screening of breastfeeding mothers taking codeine will allow for the successful identification of mother-infant pairs susceptible to adverse events and to prevent these adverse events by personalizing their medication to their genetics.
Read the detailed description
Currently, the opioid analgesic codeine is commonly administered to breastfeeding mothers after Caesarean section for pain relief. Codeine was originally considered safe to use while breastfeeding however, increased risk of adverse drug reactions has been demonstrated in mothers taking codeine, as well as their breastfed infants, when the mother possesses a genetic variation resulting in cytochrome P450 2D6 (CYP2D6) ultra-rapid metabolizer (UM) phenotype. On average, most people convert about 10-15% of their codeine dose to morphine resulting in pain relief however, UM individuals can convert up to 50% of their codeine doses into active morphine. As many as 4% of North Americans may be UMs and these mothers and their breastfed infants are at high risk of serious adverse events despite "safe" codeine dosing due to morphine overproduction and accumulation in the mother and her breast milk. Observed side effects include severe sedation, decreased rate and depth of breathing and even infant death. In response to this problem, our hospital-based clinical trial strives to identify at-risk UM mother-infant pairs by performing a genetic test on non-invasive, voluntary saliva samples from mothers giving birth by Caesarean section and who will need codeine for pain relief while breastfeeding. We believe that this test will allow us to reliably identify at-risk UM mother-infant pairs and prevent adverse drug reactions in both by tailoring analgesic therapy to their genetic results: mothers identified as being UMs will be given other suitable analgesics, such as ibuprofen, in place of codeine-containing preparations. We propose that this prospective study will generate high-level data supporting the cost-effective genetic screening of mothers who will be taking codeine while breastfeeding before they begin taking their medications. Such testing is currently possible on a nation-wide scale through collaboration with the Canadian Pharmacogenomics Network for Drug Safety (CPNDS).
- Being tested
- Cytochrome P450 2D6 (CYP2D6) genetic screening.
- Keywords
- CYP2D6, Genetic Polymorphism, codeine, breastfeeding
- Medical subject headings
- Breast Feeding
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cytochrome P450 2D6 (CYP2D6) genetic screening.Genetic
Genetic screening for cytochrome P450 2D6 (CYP2D6) polymorphism will be conducted on genetic information obtained from non-invasive salivary samples.
| Study group | Role | What they receive |
|---|---|---|
| Observant | Individuals within this group will receive pharmacotherapy according to the established institutional guidelines. Receives: Genetic: Cytochrome P450 2D6 (CYP2D6) genetic screening. | |
| Prospective CYP2D6 genetic screening | Individuals within the prospective group will receive their CYP2D6 genotype results prior to pharmacotherapy and their analgesic regimen will be tailored to their genetic results. Receives: Genetic: Cytochrome P450 2D6 (CYP2D6) genetic screening. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of maternal and neonatal CNS depression in the prospective pharmacogenetic screening group to that of a retrospectively screened population
Measured: 5-8 days post c-section surgery
Secondary outcomes (3)
Incidence of the phase II uridine diphosphate glucuronyltransferase 2B7 (UGT2B7)*2/*2 variant which has been associated with higher morphine 6-glucuronide to morphine ratios.
Measured: Minimum 1 week prior to c-section
Incidence of the C3435T polymorphism in the multi-drug resistance gene (MDR1) which has been associated with significantly greater pain relief from morphine treatment.
Measured: Minimum 1 week prior to c-section
Incidence of the A118G polymorphism in the opioid receptor 1 (OPRM1) which has been associated with reduced response to morphine treatment.
Measured: Minimum 1 week prior to c-section
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2010 (estimated)
- Study start24 Feb 2009
- Primary completion31 Dec 2012
- Study completion31 Dec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cytochrome P450 2D6 Ultra-rapid MetabolismStudies of the same condition, open and under way.
- More trials run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sThe 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
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 330 participants (actual)
Sponsor and investigators
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gideon Koren, MD, Principal investigator, Western University, Canada
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01050400
- Sponsor's protocol ID
- R-09-442
- Status last verified
- Aug 2017
- First submitted
- 11 Jan 2010
- Last updated
- 28 Aug 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CYP2D6 Screening for Adverse Drug Reactions to Codeine in Breast Milk
- ClinicalTrials.gov ID
- NCT01050400
- Acronym / sponsor ID
- R-09-442
- Keywords
- CYP2D6, Genetic Polymorphism, codeine, breastfeeding
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 330 participants (actual)
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sUniversity, hospital or other
- Study start
- 24 Feb 2009 (actual)
- Primary completion
- 31 Dec 2012 (actual)
- Study completion
- 31 Dec 2012 (actual)
- First posted
- 15 Jan 2010 (estimated)
- 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.
The purpose of this study is to determine if non-invasive salivary genetic screening of breastfeeding mothers taking codeine will allow for the successful identification of mother-infant pairs susceptible to adverse events and to prevent these adverse events by personalizing their medication to their genetics.
Detailed description
Currently, the opioid analgesic codeine is commonly administered to breastfeeding mothers after Caesarean section for pain relief. Codeine was originally considered safe to use while breastfeeding however, increased risk of adverse drug reactions has been demonstrated in mothers taking codeine, as well as their breastfed infants, when the mother possesses a genetic variation resulting in cytochrome P450 2D6 (CYP2D6) ultra-rapid metabolizer (UM) phenotype. On average, most people convert about 10-15% of their codeine dose to morphine resulting in pain relief however, UM individuals can convert up to 50% of their codeine doses into active morphine. As many as 4% of North Americans may be UMs and these mothers and their breastfed infants are at high risk of serious adverse events despite "safe" codeine dosing due to morphine overproduction and accumulation in the mother and her breast milk. Observed side effects include severe sedation, decreased rate and depth of breathing and even infant death. In response to this problem, our hospital-based clinical trial strives to identify at-risk UM mother-infant pairs by performing a genetic test on non-invasive, voluntary saliva samples from mothers giving birth by Caesarean section and who will need codeine for pain relief while breastfeeding. We believe that this test will allow us to reliably identify at-risk UM mother-infant pairs and prevent adverse drug reactions in both by tailoring analgesic therapy to their genetic results: mothers identified as being UMs will be given other suitable analgesics, such as ibuprofen, in place of codeine-containing preparations. We propose that this prospective study will generate high-level data supporting the cost-effective genetic screening of mothers who will be taking codeine while breastfeeding before they begin taking their medications. Such testing is currently possible on a nation-wide scale through collaboration with the Canadian Pharmacogenomics Network for Drug Safety (CPNDS).
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Observant | – | Genetic: Cytochrome P450 2D6 (CYP2D6) genetic screening.Individuals within this group will receive pharmacotherapy according to the established institutional guidelines. |
| Prospective CYP2D6 genetic screening | – | Genetic: Cytochrome P450 2D6 (CYP2D6) genetic screening.Individuals within the prospective group will receive their CYP2D6 genotype results prior to pharmacotherapy and their analgesic regimen will be tailored to their genetic results. |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Women undergoing elective caesarian section surgery and planning to breastfeed while concurrently taking codeine for post-partum pain relief within St. Joseph's Hospital in London and St. Michael's Hospital in Toronto.
Key inclusion criteria (5 listed)
- Have a pre-scheduled Caesarean section
- Provide DNA for CYP2D6 genetic analysis
- Breastfeed their infants
- Take codeine-containing medication during breastfeeding (retrospective screening group and non-CYP2D6 ultrarapid metabolizers in prospective screening group)
Key exclusion criteria (2 listed)
- Mothers who do not provide consent prior to Caesarian section surgery
- Mothers who take other sedative medications besides codeine during breastfeeding (these include benzodiazepines, skeletal muscle relaxants, psychotropic agents).
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 |
|---|---|---|
| Cytochrome P450 2D6 (CYP2D6) genetic screening.Genetic screening for cytochrome P450 2D6 (CYP2D6) polymorphism will be conducted on genetic information obtained from non-invasive salivary samples. | Genetic | Observant, Prospective CYP2D6 genetic screening |
Primary outcome
Incidence of maternal and neonatal CNS depression in the prospective pharmacogenetic screening group to that of a retrospectively screened population
Time frame: 5-8 days post c-section surgery
3 secondary outcomes
Incidence of the phase II uridine diphosphate glucuronyltransferase 2B7 (UGT2B7)*2/*2 variant which has been associated with higher morphine 6-glucuronide to morphine ratios.
Time frame: Minimum 1 week prior to c-section
Incidence of the C3435T polymorphism in the multi-drug resistance gene (MDR1) which has been associated with significantly greater pain relief from morphine treatment.
Time frame: Minimum 1 week prior to c-section
Incidence of the A118G polymorphism in the opioid receptor 1 (OPRM1) which has been associated with reduced response to morphine treatment.
Time frame: Minimum 1 week prior to c-section
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 28 Aug 2017.
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.
Gideon Koren, MD principal investigator
Western University, Canada
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 Cytochrome P450 2D6 Ultra-rapid Metabolism, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's 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 5 inclusion and 2 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 28 Aug 2017. 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?
Incidence of maternal and neonatal CNS depression in the prospective pharmacogenetic screening group to that of a retrospectively screened population (time frame: 5-8 days post c-section surgery). 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 28 Aug 2017.