CYTRAM (Cytochrome P450, Tramadol)

This study has been completed.
Sponsor:
Information provided by:
University Hospital, Caen
ClinicalTrials.gov Identifier:
NCT00952159
First received: August 3, 2009
Last updated: July 1, 2011
Last verified: July 2011
  Purpose

Many methods to detect CYP2D6 poor metabolizers have been validated. Some of them are based on phenotyping (metabolism of dextromethorphan or debrisoquine) and some others on genotyping. Up to now, CYP2D6 pharmacogenetics has been restricted to the field of research, in spite of poor metabolizer profile concerns 5 to 10 % of caucasian population. Nevertheless, the polymorphism of CYP2D6 is responsible for the metabolism of many drugs, particularly of two opioids involved in pain management: codeine and tramadol, their metabolites representing the most effective part of the drug effect. So prescribing codeine or tramadol in a patient poor metabolizer for the CYP2D6 is likely to be ineffective in pain management.

O-demethyl-tramadol, the metabolite of tramadol via CYP2D6, is important to consider because its analgesic effect is 2 to 4 times more potent than tramadol.

The investigators propose to phenotype CYP2D6 in post-operative patients treated by tramadol by monitoring seric concentrations of O-demethyl tramadol and tramadol to make a ratio in comparison with genotype, and to find a threshold to determine poor metabolizers. As already described, genotyping CYP2D6 will use a rapid detection method of the alleles implicated in poor metabolizer status (CYP2D6*3, *4, *5 et *6) in a Caucasian population. Sampling will be executed at two times (H24 and H48 after surgery) and only with blood (three EDTA tubes) during the post-operative monitoring of the patients. This study is likely to include 320 post-operative patients treated with intravenous tramadol during one year in three university hospitals centers (CHU of Caen, Creteil and Rouen).

The first aim of this study is the validation of monitoring seric concentrations of O-demethyl-tramadol and tramadol to make the ratio in order to detect CYP2D6 poor metabolizers in therapeutic situation, comparing the result with genotyping. The finding of a poor metabolizer status in a patient will make the choice of analgesic drugs easier, avoiding tramadol and codeine. The final objective of this research is to be able to determine the CYP2D6 phenotype in a patient treated by tramadol without a good analgesia. By a single take of blood and a rapid response, this method should be liked to improve pain management. Furthermore, CYP2D6 phenotyping is interesting for the patient because many other drugs depend on this way of metabolism.


Condition Intervention
Post-operative Patients Treated by Tramadol
Biological: Monitoring seric concentrations of O-demethyl-tramadol and tramadol

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Validation of a New Method to Detect CYP2D6 Poor Metabolizers by Monitoring Seric Concentrations of O-demethyl-tramadol and Tramadol to Make a Ratio in Comparison With Genotyping in Post-operative Patients Treated With Intravenous Tramadol

Resource links provided by NLM:


Further study details as provided by University Hospital, Caen:

Primary Outcome Measures:
  • To phenotype CYP2D6 in post-operative patients treated by tramadol by monitoring seric concentrations of O-demethyl tramadol and tramadol to make a ratio in comparison with genotype, and to find a threshold to determine poor metabolizers. [ Time Frame: H24 and H48 after surgery ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

We propose to phenotype CYP2D6 in post-operative patients treated by tramadol by monitoring seric concentrations of O-demethyl tramadol and tramadol to make a ratio in comparision with genotype, and to find a threeshold to determine poor metabolizers. As already described, genotyping CYP2D6 will use a rapid detection method of the alleles implicated in poor metabolizer status (CYP2D6*3, *4, *5 et *6) in a caucasian population


Enrollment: 301
Study Start Date: April 2010
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Not Poor metabolizer Biological: Monitoring seric concentrations of O-demethyl-tramadol and tramadol
The first aim of this study is the validation of monitoring seric concentrations of O-demethyl-tramadol and tramadol to make the ratio in order to detect CYP2D6 poor metabolizers in therapeutic situation, comparing the result with genotyping. The finding of a poor metabolizer status in a patient will make the choice of analgesic drugs easier, avoiding tramadol and codeine. The final objective of this research is to be able to determine the CYP2D6 phenotype in a patient treated by tramadol without a good analgesia. By a single take of blood and a rapid response, this method should be liked to improve pain management. Furthermore, CYP2D6 phenotyping is interesting for the patient because many other drugs depend on this way of metabolism.
Poor metabolizer Biological: Monitoring seric concentrations of O-demethyl-tramadol and tramadol
The first aim of this study is the validation of monitoring seric concentrations of O-demethyl-tramadol and tramadol to make the ratio in order to detect CYP2D6 poor metabolizers in therapeutic situation, comparing the result with genotyping. The finding of a poor metabolizer status in a patient will make the choice of analgesic drugs easier, avoiding tramadol and codeine. The final objective of this research is to be able to determine the CYP2D6 phenotype in a patient treated by tramadol without a good analgesia. By a single take of blood and a rapid response, this method should be liked to improve pain management. Furthermore, CYP2D6 phenotyping is interesting for the patient because many other drugs depend on this way of metabolism.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Post-operative patients treated by tramadol

Criteria

Inclusion Criteria:

  • age > 18 years, post-operative patient treated with intravenous tramadol
  • Caucasian origin
  • take of blood at H24 and H48 in the post-operative monitoring

Exclusion Criteria:

  • patient having already been included in the study
  • patient taking opioid drugs before surgery
  • patient taking one or more drugs inhibiting the CYP2D6 before or during surgery
  • pregnancy or breast feeding patients having one or more contraindications for taking tramadol in post-operative analgesia
  • hepatocellular incapacity (TP < 70%)
  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: NCT00952159

Locations
France
Caen University Hospital
Caen, France, 14033
Private Clinic Saint-Martin
Caen, France, 14000
Créteil University Hospital
Créteil, France
Rouen University Hospital
Rouen, France, 76000
Sponsors and Collaborators
University Hospital, Caen
Investigators
Principal Investigator: Blandine de la Gastine, MD University Hospital, Caen
  More Information

No publications provided

Responsible Party: Patrick MICHEL (research and strategy manager), Caen University Hospital
ClinicalTrials.gov Identifier: NCT00952159     History of Changes
Other Study ID Numbers: 2009-A00380-57, 09-013
Study First Received: August 3, 2009
Last Updated: July 1, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Caen:
tramadol
CYP2D6
O-demethyl-tramadol
poor metabolizer
genotyping
phenotyping

Additional relevant MeSH terms:
Tramadol
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014