CYP2D6 Polymorphism in Patients of General Practice in Austria

NCT03859622 | Completed Results

• 1 other identifier: KarlLandsteinerISGM CYP2D6
• Study Type: observational
• Target: 289
• Locations: 1 country
• Sites: 1

Brief Summary

The CYP 2D6 enzyme metabolizes a significant number of drugs frequently prescribed in general practice/ family medicine. Various genetically different variants define if the patient is an ultra-rapid (UM), an normal (NM) (the normal case), an intermediate (IM) or a poor metabolizer (PM). It is estimated that approximately 20- 25 % of frequently described drugs are activated to more active or metabolized to ineffective or less effective drugs by CYP 2D6. Substrates of CYP 2D6 are mainly antidepressants, neuroleptics, opioids (e.g. codeine), beta-blockers, anti-arrhythmic drugs and various other single drugs. In case of an UM a drug can be metabolized too rapidly losing its therapeutic effect, requiring a higher dosage, or it can have a toxic effect, if it is converted too rapidly in the effective form (e.g. codeine). If metabolized too slowly (PM) it can accumulate and reach toxic levels. In this observational study (1) data relating to the number of patients of a single Austrian general practice receiving one or more drugs metabolized by CYP 2D6 are collected by extracting their electronic records of the last 3 years. In addition (2) consecutive patients with unknown genetic status of their CYP 2D6 enzyme visiting the surgery for a routine blood test due to various reasons, are additionally tested for their CYP 2D6 metabolizing status, if they actually take a drug metabolized by CYP 2D6. The aim of the study is to generate CYP 2D6 polymorphism data from Caucasian patients of an average Austrian general practice for the first time, which allows to group patients according to their NM, UM, IM and PM status. This can be of considerable clinical relevance when prescribing specific drugs. This study tries to investigate in how many patients the knowledge of the CYP 2D6 metabolizing status could have an influence on choosing the actually prescribed drug. In addition we plan to describe the distribution of frequent and relevant CYP 2D6 alleles including their combinations in patients of an average Austrian general practice for comparison reasons with other Caucasian populations.

Conditions

Disorder Due Cytochrome P450 CYP2D6 Variant

Keywords

Cytochrome P 450 CYP2D6 Variants; Genetic polymorphism; Practice, Family; Drug metabolism

Outcome Measures

Primary Outcomes (3)

• Frequency of Metabolizer Status (PM, IM, NM, UM) in Patients

  Remark: each participant possesses a) two individual CYP2D6 alleles, b) from the combination of these two alleles one individual genotype is derived and c) from this genotype the genetically determined metabolizer status (PM, IM, NM, UM) is derived. A patient can be considered a ultra-rapid (UM), a normal (NM), an intermediate (IM), or a poor metabolizer (PM) of a given drug

  1 Year

• Frequency of CYP2D6 Alleles in Patients

  The frequency of 19 different CYP2D6 alleles in 287 patients is determined. In 2 out of all 289 patients the determination was not possible due to technical problems. Remark: each participant possesses a) two individual CYP2D6 alleles, b) from the combination of these two alleles one individual genotype is derived and c) from this genotype the genetically determined metabolizer status (PM, IM, NM, UM) is derived.

  1 Year

• Frequency of CYP2D6 Genotypes in Patients

  The frequency of 61 different CYP2D6 genotypes in 287 patients is determined. In 2 out of all 289 patients the determination was not possible due to technical problems. Remark: each participant possesses a) two individual CYP2D6 alleles, b) from the combination of these two alleles one individual genotype is derived and c) from this genotype the genetically determined metabolizer status (PM, IM, NM, UM) is derived.

  1 Year

Secondary Outcomes (2)

• Number of Participants in Whom the Family Physician Considered Prior Knowledge of Their Metabolizer Status Important Before the CYP2D6-specific Drug Was Prescriped.

  1 Year

• Specific Number of Patients of the Whole Practice Population Whose Electronic Health Records (EHRs) Were Assessed.

  1 Year

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Unselected consecutive patients of an Austrian general practice suffering from chronic diseases visting the practice office for a routine blood test

You may qualify if:

• Patients with clinical diagnosis of hypertension, diabetes, chronic heart failure, hyperlipidemias, depression, schizophrenia, cardial arrhythmias, thyroid diseases and dementia

You may not qualify if:

• acute infectious diseases

Sponsors & Collaborators

• Karl Landsteiner Institute for Systematics in General Medicine: lead

Study Sites (1)

Practice Office

Angern, Lower Austria, A 2261, Austria

Location

Related Publications (1)

• Kamenski G, Ayazseven S, Berndt A, Fink W, Kamenski L, Zehetmayer S, Puhringer H. Clinical Relevance of CYP2D6 Polymorphisms in Patients of an Austrian Medical Practice: A Family Practice-Based Observational Study. Drugs Real World Outcomes. 2020 Mar;7(1):63-73. doi: 10.1007/s40801-019-00177-4.

  PMID: 31863305 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

DNA extraction from peripheral white blood cells

Results Point of Contact

• Title: Dr.med.Gustav Kamenski
• Organization: Karl Landsteiner Institute of General Medicine

kamenski@aon.at

+4322832226

Study Officials

• Gustav Kamenski

  Karl Landsteiner Institute for Systematics in General Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: General Practitioner/Family Physician

Study Record Dates

• First Submitted: October 20, 2018
• First Posted: March 1, 2019
• Study Start: October 9, 2017
• Primary Completion: October 9, 2018
• Study Completion: October 9, 2018
• Last Updated: October 30, 2019
• Results First Posted: October 30, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: 2018 and 2019
• Access Criteria: Researchers working in the pharmacogenetic field

Locations

AU (1)