Response to Donepezil, Drug Plasma Concentration and the CYP2D6 and APOE Genetic Polymorphisms (NCT03349320) | Clinical Trial Compass
CompletedNot Applicable
Response to Donepezil, Drug Plasma Concentration and the CYP2D6 and APOE Genetic Polymorphisms
37 participantsStarted 2009-06
Plain-language summary
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.
Who can participate
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion Criteria:
* Patients fulfilling the National Institute on Aging and the Alzheimer's Association diagnostic criteria of probable AD dementia or the NINDS-AIREN (National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherché et l'Enseignement en Neurosciences) diagnostic criteria of AD with cerebrovascular disease (AD + CVD)
* Patients presenting mild or moderate dementia according to the Clinical Dementia Rating (CDR), i.e., CDR 1 or 2, respectively
Exclusion Criteria:
* Patients treated with ChEI or memantine before study entry
* Patients diagnosed with frontotemporal dementia, dementia with Lewy bodies or vascular dementia,
* Patients classified as CDR 3 or with Mild Cognitive Impairment
* Illiterate patients
* Disagreement between the first investigator and the treating physician regarding the diagnosis
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Association among donepezil serum concentration after 3, 6, and 12 months of treatment onset and clinical response.