Response to Donepezil, Drug Plasma Concentration and the CYP2D6 and APOE Genetic Polymorphisms
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|ClinicalTrials.gov Identifier: NCT03349320|
Recruitment Status : Completed
First Posted : November 21, 2017
Last Update Posted : December 18, 2017
Pharmacological treatment of AD is currently based on cholinesterase inhibitors (ChEI) and memantine, which have been shown to lead to modest, although effective, clinical benefits. Donepezil is a ChEI metabolized through the cytochrome P (CYP) 450, primarily by the 3A4 and 2D6 isoforms. The CYP2D6 gene presents polymorphisms that can alter its expression. The plasma therapeutic level ranges from 30 to 75 ng/mL, and 50% of acetylcholinesterase inhibition is achieved when the concentration reaches 15.6 ng/mL. An optimal plasma level is greater than 50 ng/mL.
These polymorphisms may influence the individual's response to treatment with donepezil and the concentration of the drug in AD patients, without achieving the desired effect. However, most of the individuals are EM, i.e., the metabolism of the drug occurs according to the expected kinetics and is associated with the presence of one or two wild-type alleles.
Objective: investigate the pattern of clinical response to donepezil in a group of patients with AD and AD with cerebrovascular disease (CVD) in relation to the plasmatic concentration of donepezil and polymorphisms of the CYP2D6 and apolipoprotein E (APOE) genes.
|Condition or disease|
|Late Onset Alzheimer Disease|
|Study Type :||Observational|
|Actual Enrollment :||37 participants|
|Official Title:||Clinical Response to Donepezil in Mild and Moderate Dementia: Relationship to the Drug Plasma Concentration and the CYP2D6 and APOE Genetic Polymorphisms|
|Actual Study Start Date :||June 2009|
|Actual Primary Completion Date :||March 2013|
|Actual Study Completion Date :||March 2013|
- Association among donepezil serum concentration after 3, 6, and 12 months of treatment onset and clinical response. [ Time Frame: September, 2009 until March, 2013 ]Evaluate the serum concentration of donepezil after 3, 6, and 12 months of treatment onset in patients considered good responders (i.e., those who had an increment >1 in MMSE in comparison to baseline assessment after 1 year of donepezil treatment) in contrast to those considered bad responders (i.e., who had a reduction, a stabilization or an increment of 1 in MMSE in comparison to baseline assessment after 1 year of donepezil treatment).
- Evaluation of baseline cognitive performance [ Time Frame: June, 2009 until March, 2012 ]Assess the baseline cognitive performance among included patients (notedly, MMSE test, CERAD batteries, and in the Pfeffer Functional Activities Questionnaire).
- Evaluation of CYP2D6 and APOE polymorphisms [ Time Frame: June, 2009 until March, 2012 ]Evaluation of CYP2D6 and APOE polymorphisms among included patients.
- Evaluate donepezil serum concentration after 3 months of treatment onset. [ Time Frame: September, 2009 until June, 2012 ]Measurement of donepezil serum concentration after 3 months of treatment onset.
- Evaluate donepezil serum concentration after 6 months of treatment onset. [ Time Frame: December, 2009 until September, 2012 ]Measurement of donepezil serum concentration after 6 months of treatment onset.
- Evaluate donepezil serum concentration after 12 months of treatment onset. [ Time Frame: June, 2010 until March, 2013 ]Measurement of donepezil serum concentration after 12 months of treatment onset.
Biospecimen Retention: Samples With DNA
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Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03349320
|Study Chair:||Paulo Caramelli, MD, PhD||Federal University of Minas Gerais|