Late Onset Alzheimer DiseaseNCT03349320
Response to Donepezil, Drug Plasma Concentration and the CYP2D6 and APOE Genetic Polymorphisms
An observational study of Late Onset Alzheimer Disease, run by Federal University of Minas Gerais.
Trial 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. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Late Onset Alzheimer Disease
- How many people
- 37 participants
- Where
- No sites listed yet
- Study dates
- Jun 2009to Mar 2013
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: A longitudinal, naturalist study, conducted at the Geriatric Outpatient Clinic of the Hospital das Clínicas at the Federal University of Minas Gerais (UFMG), in Belo Horizonte (MG), Brazil. The sample comprised patients evaluated from June, 2009 until March, 2013
Who may be able to join
- 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
Who cannot join
- 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
About this study
Official title: Clinical Response to Donepezil in Mild and Moderate Dementia: Relationship to the Drug Plasma Concentration and the CYP2D6 and APOE Genetic Polymorphisms
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.
Read the detailed description
Patients taking donepezil were seen four times (from June 2009 to March 2013) and were submitted to the MMSE test, the Consortium to Establish a Registry for Alzheimer'sDisease battery (CERAD), and the Pfeffer Functional Activities Questionnaire. CERAD memory evaluation was further divided into five components: incidental recall (CERAD151 INC), immediate recall 1 and 2 (CERAD-RM1, CERAD-RM2, respectively) and delayed recall after five minutes (CERAD-R). Each aspect was analyzed individually and compared between groups at baseline and after 12 months of treatment with donepezil. All patients had blood samples (10mL) collected to obtain donepezil plasmatic concentration (DPC) measurements and for APOE and CYP2D6 genotyping.
- Conditions
- Late Onset Alzheimer Disease
- Keywords
- Alzheimer, APOE, CYP2D6, Donepezil, Genetics
- Medical subject headings
- Alzheimer Disease
What is being measured
The primary outcome is the main question the study is designed to answer.
Association among donepezil serum concentration after 3, 6, and 12 months of treatment onset and clinical response.
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).
Measured: September, 2009 until March, 2013
Secondary outcomes (5)
Evaluation of baseline cognitive performance
Assess the baseline cognitive performance among included patients (notedly, MMSE test, CERAD batteries, and in the Pfeffer Functional Activities Questionnaire).
Measured: June, 2009 until March, 2012
Evaluation of CYP2D6 and APOE polymorphisms
Evaluation of CYP2D6 and APOE polymorphisms among included patients.
Measured: June, 2009 until March, 2012
Evaluate donepezil serum concentration after 3 months of treatment onset.
Measurement of donepezil serum concentration after 3 months of treatment onset.
Measured: September, 2009 until June, 2012
Evaluate donepezil serum concentration after 6 months of treatment onset.
Measurement of donepezil serum concentration after 6 months of treatment onset.
Measured: December, 2009 until September, 2012
Evaluate donepezil serum concentration after 12 months of treatment onset.
Measurement of donepezil serum concentration after 12 months of treatment onset.
Measured: June, 2010 until March, 2013
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2017
- Study startJun 2009
- Primary completionMar 2013
- Study completionMar 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Late Onset Alzheimer DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Federal University of Minas Gerais
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Luís Felipe José Ravic de Miranda, Federal University of Minas Gerais
- Investigators
- Paulo Caramelli, MD, PhD, Study chair, Federal University of Minas Gerais
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03349320
- Sponsor's protocol ID
- 0172 /2010
- Status last verified
- Dec 2017
- First submitted
- 21 Jun 2017
- Last updated
- 18 Dec 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Response to Donepezil in Mild and Moderate Dementia: Relationship to the Drug Plasma Concentration and the CYP2D6 and APOE Genetic Polymorphisms
- ClinicalTrials.gov ID
- NCT03349320
- Acronym / sponsor ID
- 0172 /2010
- Conditions
- Late Onset Alzheimer Disease
- Keywords
- Alzheimer, APOE, CYP2D6, Donepezil, Genetics
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Federal University of Minas GeraisUniversity, hospital or other
- Study start
- Jun 2009 (actual)
- Primary completion
- Mar 2013 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 21 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Patients taking donepezil were seen four times (from June 2009 to March 2013) and were submitted to the MMSE test, the Consortium to Establish a Registry for Alzheimer'sDisease battery (CERAD), and the Pfeffer Functional Activities Questionnaire. CERAD memory evaluation was further divided into five components: incidental recall (CERAD151 INC), immediate recall 1 and 2 (CERAD-RM1, CERAD-RM2, respectively) and delayed recall after five minutes (CERAD-R). Each aspect was analyzed individually and compared between groups at baseline and after 12 months of treatment with donepezil. All patients had blood samples (10mL) collected to obtain donepezil plasmatic concentration (DPC) measurements and for APOE and CYP2D6 genotyping.
Study design
- Observational model
- Other
- Time perspective
- Prospective
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- A longitudinal, naturalist study, conducted at the Geriatric Outpatient Clinic of the Hospital das Clínicas at the Federal University of Minas Gerais (UFMG), in Belo Horizonte (MG), Brazil. The sample comprised patients evaluated from June, 2009 until March, 2013
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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).
5 secondary outcomes
Evaluation of baseline cognitive performance
Time frame: June, 2009 until March, 2012
Evaluation of CYP2D6 and APOE polymorphisms
Time frame: June, 2009 until March, 2012
Evaluate donepezil serum concentration after 3 months of treatment onset.
Time frame: September, 2009 until June, 2012
Evaluate donepezil serum concentration after 6 months of treatment onset.
Time frame: December, 2009 until September, 2012
Evaluate donepezil serum concentration after 12 months of treatment onset.
Time frame: June, 2010 until March, 2013
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paulo Caramelli, MD, PhD study chair
Federal University of Minas Gerais
Questions about this trial
What is this clinical trial studying?
An observational study of Late Onset Alzheimer Disease, run by Federal University of Minas Gerais.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Association among donepezil serum concentration after 3, 6, and 12 months of treatment onset and clinical response. (time frame: September, 2009 until March, 2013). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2017.