CYP2D6 Screening for Adverse Drug Reactions to Codeine in Breast Milk

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2010 by Lawson Health Research Institute.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Lawson Health Research Institute
ClinicalTrials.gov Identifier:
NCT01050400
First received: January 11, 2010
Last updated: January 13, 2010
Last verified: January 2010
  Purpose

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.


Condition Intervention
Cytochrome P450 2D6 Ultra-rapid Metabolism
Genetic: Cytochrome P450 2D6 (CYP2D6) genetic screening.

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: CYP2D6 Screening for Adverse Drug Reactions to Codeine in Breast Milk

Resource links provided by NLM:


Further study details as provided by Lawson Health Research Institute:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Saliva and breast milk samples.


Estimated Enrollment: 660
Study Start Date: October 2009
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Observant
Individuals within this group will receive pharmacotherapy according to the established institutional guidelines.
Genetic: 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.
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.
Genetic: 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.

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).

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
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.

Criteria

Inclusion Criteria:

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)

Exclusion Criteria:

  • 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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01050400

Contacts
Contact: Catherine Ciszkowski, BMSc 519-661-2111 ext 83221 dnastudy@uwo.ca

Locations
Canada, Ontario
St. Joseph's Hospital Recruiting
London, Ontario, Canada, N6A 4V2
Principal Investigator: Gideon Koren, MD         
Sponsors and Collaborators
Lawson Health Research Institute
Investigators
Principal Investigator: Gideon Koren, MD University of Western Ontario, Canada
  More Information

No publications provided

Responsible Party: Dr. Gideon Koren, University of Western Ontario
ClinicalTrials.gov Identifier: NCT01050400     History of Changes
Other Study ID Numbers: R-09-442
Study First Received: January 11, 2010
Last Updated: January 13, 2010
Health Authority: Canada: Ethics Review Committee

Keywords provided by Lawson Health Research Institute:
CYP2D6
Genetic Polymorphism
codeine
breastfeeding

Additional relevant MeSH terms:
Drug-Related Side Effects and Adverse Reactions
Chemically-Induced Disorders
Codeine
Analgesics
Analgesics, Opioid
Antitussive Agents
Central Nervous System Agents
Central Nervous System Depressants
Narcotics
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014