Alzheimer DiseaseNCT05532644
Correlation of P-glycoprotein Polymorphisms With Microbial Metabolites in Patients With Alzheimer's Disease on Medication
An observational study of Alzheimer Disease, run by Aristotle University Of Thessaloniki at 1 site in Greece.
Trial summary
The importance of the proposed study concerns the understanding of the way in which each drug acts in each organism separately, both at the genome level and at the microbiome level. Read more about this study
- Who is it for?
- Ages 50 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- AD drugs
- How many people
- 135 participants
- Where
- 1 siteGreece
- Study dates
- Sep 2022to Sep 2024
- 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 50 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients with verified AD receiving treatment
Patients with verified AD, which are monitored in the A' Neurological Clinic of AHEPA Hospital and the Hellenic Society of Alzheimer's Disease and Related Disorders (Alzheimer Hellas), are candidates for inclusion in the study. Patients should be in a mild or moderate stage of disease and should undergo a treatment (cholinesterase inhibitors or NMDA receptor antagonists) according to international guidelines. They will form the control team before receiving treatment, and there will be a group of healthy controls.
Trial locations and contacts
1 site in 1 country.
Greece1 site
Aristotle University of Thessaloniki
Thessaloniki
Magda Tsolaki, Professor, 0030 2310 2411 56, tsolakim1@gmail.com
Emmanouela Basgiouraki, bmanwlia@yahoo.com
About this study
Official title: Correlation of P-glycoprotein Polymorphisms With Microbial Metabolites in Patients With Alzheimer's Disease (AD) on Medication
The importance of the proposed study concerns the understanding of the way in which each drug acts in each organism separately, both at the genome level and at the microbiome level. It is often observed that various treatments do not have the expected results in all patients, while, at the same time, new pathophysiological mechanisms for each disease are found. The involvement of the intestinal microbiome is one of these mechanisms and as it affects not only the progression of the disease but also the way in which drugs are metabolized (hence their action) should now be considered in every possible case. This led to the emergence of a new field of study related to personalized medicine, pharmacomicrobiomics. It includes microbiology, genomics, and pharmacology, and studies the changes that the human microbiome shows in drug exposure, action, and toxicity. However, this field is relatively new, and although there have been several reports of microbial biotransformation, there has been little in-depth research into the specificity of bacterial strains or the factors that can predict drug transformations. Therefore, this study will give the impetus for the individualized treatment, which will not only concern the genome (which is constantly evolving in recent years) but also the intestinal microbiome, which as mentioned above, is involved in many pathological conditions.
Importance of the study
Although a considerable number of studies have focused on the relationship between the microbiome and the pathogenesis of Alzheimer's Disease (AD), we have not seen any studies on the effect of drugs currently used in the treatment of AD (which are primarily cholinesterase inhibitors), such as rivastigmine, galantamine and donepezil and the NMDA (N-methyl-D-aspartate) glutamate receptor antagonist (memantine). There is also no reference to the composition and / or activity of the microbiome or to the effect of the latter on the pharmacokinetics and / or pharmacodynamics of these drugs. Also, although the human microbiome is influenced by genetic factors in the body, the effect of polymorphisms on the P-gp gene, which is involved in the pathophysiology of AD, the microbiome or its metabolites, has not been studied.
Read the detailed description
Study design
In the proposed study, the patients will be divided into those receiving cholinesterase inhibitors (rivastigmine, galantamine and donepezil) and those receiving NMDA receptor antagonist therapy (memantine), based on the treatment they follow for AD. . A medical history of patients and controls, neuropsychological assessments using the respective questionnaires used in AD (which will be repeated at the end of the study-3 months) and a stool sample will be taken. Finally, a blood sample will be taken at the beginning of treatment to study P-gp ABCB1 gene polymorphisms and RLs and LPSs levels, and one at the end of the study to examinate drug levels RLs and LPSs levels in blood.
Duration:
Based on the required number of samples (patients and controls) the collection of these will last 6 months. Laboratory tests will take place in the next 12 months. Therefore, the main part of the study (sampling, laboratory analyzes) is expected to be completed in 18 months, while the stage of processing, analysis and verification of results is expected to last 6 months. The total duration of the study is expected to be 24 months.
Number of Subjects
135 subjects.
- 45 patients receiving treatment with cholinesterase inhibitors (rivastigmine, galantamine and donepezil).
- 45 patients receiving NMDA receptor antagonist (memantine).
- 45 healthy controls.
Patient Eligibility Screening Form (ESF):
An eligibility form documenting the patient's fulfillment of the entry criteria will be completed by the assessor. The following information will be included in the ESF:
- Patient identification: Initials (First initial of first name and first initial of surname), date of birth and Patient Identification Number.
- Written informed consent will be obtained from the subject. The informed consent form must be co-signed by the physician. The nature of the study and the potential risks associated with the trial will be explained to all subject candidates and their responsible informants.
- Signature and date: the ESF may be completed by an assessor but it is required that the principal investigator/study clinician sign and date the ESF to verify eligibility of the patient for inclusion.
Measured parameters:
For each patient who will participate in the study there should be a record of personal history that will include:
- Age
- Place of residence
- Eating habits (Mediterranean diet will be recommended)
- Smoking
- Medication followed in the last year
- Duration of the disease
- Other pathological conditions
Questionnaires
The neuropsychological assessment will include the following questionnaires, which are validated in Greek elderly population:
- Mini Mental Status Examination (MMSE)
- Montreal Cognitive Assessment (MoCA)
- Geriatrics Depression Scale (GDS)
- Functional or Cognitive Assessment scale (FUCAS)
Measurement methods
- The finding of P-gp ABCB1 gene polymorphisms will be performed with isolation of DNA with appropriate kits from the blood sample and will follow PCR technique with suitable primers and DNA electrophoresis or techniques real time PCR (taqman assay).
- Levels of RLs and LPs will be measured by the method ELISA and the use of corresponding antibodies.
- Drug levels in the blood will be measured by fluid high performance chromatography coupled to mass spectrometry (HPLC / MS).
- Conditions
- Alzheimer Disease
- Being tested
- AD drugs
- Keywords
- Alzheimer's Disease, P-gp, polymorphisms, microbiome, drugs, lipopolysaccharides, rhamnolipids
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AD drugsOther
AD drugs
| Study group | Role | What they receive |
|---|---|---|
| Patients receiving cholinesterase inhibitors | Not described Receives: Other: AD drugs | |
| Patients receiving memantine | Not described Receives: Other: AD drugs | |
| Healthy people | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Genetics
The primary target of this study is the correlation of the distribution of genotypes and haplotypes of ABCB1 polymorphisms of patients with AD with Rhamnolipids (RLs) and Polysaccharides (LPSs) levels, as well as with steady-state levels of the respective drugs in the blood.
Measured: 6 months
Secondary outcomes (1)
Microbiome
A secondary aim of this study is the comparison of the levels of RLs and LPSs as bacterial metabolites, in patients with AD following specific treatment with those of healthy controls and correlation with the course of the disease.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2022
- Study startSep 2022 (estimated)
- Primary completionDec 2023 (estimated)
- Study completionSep 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Aristotle University Of ThessalonikiThe sponsor's other registered studies.
- 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
- Case crossover
- Time perspective
- Prospective
- Enrolment
- 135 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Aristotle University Of Thessaloniki
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Magda Tsolaki, Aristotle University Of Thessaloniki
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05532644
- Sponsor's protocol ID
- MicroGeneAD
- Status last verified
- Sep 2022
- First submitted
- 4 Sep 2022
- Last updated
- 8 Sep 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Correlation of P-glycoprotein Polymorphisms With Microbial Metabolites in Patients With Alzheimer's Disease (AD) on Medication
- ClinicalTrials.gov ID
- NCT05532644
- Acronym / sponsor ID
- MicroGeneAD
- Conditions
- Alzheimer Disease
- Keywords
- Alzheimer's Disease, P-gp, polymorphisms, microbiome, drugs, lipopolysaccharides, rhamnolipids
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 135 participants (estimated)
- Lead sponsor
- Aristotle University Of ThessalonikiUniversity, hospital or other
- Study start
- Sep 2022 (estimated)
- Primary completion
- Dec 2023 (estimated)
- Study completion
- Sep 2024 (estimated)
- First posted
- 8 Sep 2022 (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.
The importance of the proposed study concerns the understanding of the way in which each drug acts in each organism separately, both at the genome level and at the microbiome level. It is often observed that various treatments do not have the expected results in all patients, while, at the same time, new pathophysiological mechanisms for each disease are found. The involvement of the intestinal microbiome is one of these mechanisms and as it affects not only the progression of the disease but also the way in which drugs are metabolized (hence their action) should now be considered in every possible case. This led to the emergence of a new field of study related to personalized medicine, pharmacomicrobiomics. It includes microbiology, genomics, and pharmacology, and studies the changes that the human microbiome shows in drug exposure, action, and toxicity. However, this field is relatively new, and although there have been several reports of microbial biotransformation, there has been little in-depth research into the specificity of bacterial strains or the factors that can predict drug transformations. Therefore, this study will give the impetus for the individualized treatment, which will not only concern the genome (which is constantly evolving in recent years) but also the intestinal microbiome, which as mentioned above, is involved in many pathological conditions.
Importance of the study
Although a considerable number of studies have focused on the relationship between the microbiome and the pathogenesis of Alzheimer's Disease (AD), we have not seen any studies on the effect of drugs currently used in the treatment of AD (which are primarily cholinesterase inhibitors), such as rivastigmine, galantamine and donepezil and the NMDA (N-methyl-D-aspartate) glutamate receptor antagonist (memantine). There is also no reference to the composition and / or activity of the microbiome or to the effect of the latter on the pharmacokinetics and / or pharmacodynamics of these drugs. Also, although the human microbiome is influenced by genetic factors in the body, the effect of polymorphisms on the P-gp gene, which is involved in the pathophysiology of AD, the microbiome or its metabolites, has not been studied.
Detailed description
Study design
In the proposed study, the patients will be divided into those receiving cholinesterase inhibitors (rivastigmine, galantamine and donepezil) and those receiving NMDA receptor antagonist therapy (memantine), based on the treatment they follow for AD. . A medical history of patients and controls, neuropsychological assessments using the respective questionnaires used in AD (which will be repeated at the end of the study-3 months) and a stool sample will be taken. Finally, a blood sample will be taken at the beginning of treatment to study P-gp ABCB1 gene polymorphisms and RLs and LPSs levels, and one at the end of the study to examinate drug levels RLs and LPSs levels in blood.
Duration:
Based on the required number of samples (patients and controls) the collection of these will last 6 months. Laboratory tests will take place in the next 12 months. Therefore, the main part of the study (sampling, laboratory analyzes) is expected to be completed in 18 months, while the stage of processing, analysis and verification of results is expected to last 6 months. The total duration of the study is expected to be 24 months.
Number of Subjects
135 subjects.
- 45 patients receiving treatment with cholinesterase inhibitors (rivastigmine, galantamine and donepezil).
- 45 patients receiving NMDA receptor antagonist (memantine).
- 45 healthy controls.
Patient Eligibility Screening Form (ESF):
An eligibility form documenting the patient's fulfillment of the entry criteria will be completed by the assessor. The following information will be included in the ESF:
- Patient identification: Initials (First initial of first name and first initial of surname), date of birth and Patient Identification Number.
- Written informed consent will be obtained from the subject. The informed consent form must be co-signed by the physician. The nature of the study and the potential risks associated with the trial will be explained to all subject candidates and their responsible informants.
- Signature and date: the ESF may be completed by an assessor but it is required that the principal investigator/study clinician sign and date the ESF to verify eligibility of the patient for inclusion.
Measured parameters:
For each patient who will participate in the study there should be a record of personal history that will include:
- Age
- Place of residence
- Eating habits (Mediterranean diet will be recommended)
- Smoking
- Medication followed in the last year
- Duration of the disease
- Other pathological conditions
Questionnaires
The neuropsychological assessment will include the following questionnaires, which are validated in Greek elderly population:
- Mini Mental Status Examination (MMSE)
- Montreal Cognitive Assessment (MoCA)
- Geriatrics Depression Scale (GDS)
- Functional or Cognitive Assessment scale (FUCAS)
Measurement methods
- The finding of P-gp ABCB1 gene polymorphisms will be performed with isolation of DNA with appropriate kits from the blood sample and will follow PCR technique with suitable primers and DNA electrophoresis or techniques real time PCR (taqman assay).
- Levels of RLs and LPs will be measured by the method ELISA and the use of corresponding antibodies.
- Drug levels in the blood will be measured by fluid high performance chromatography coupled to mass spectrometry (HPLC / MS).
Study design
- Observational model
- Case crossover
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Patients receiving cholinesterase inhibitors | – | Other: AD drugs |
| Patients receiving memantine | – | Other: AD drugs |
| Healthy people | – | – |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with verified AD receiving treatment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AD drugsAD drugs | Other | Patients receiving cholinesterase inhibitors, Patients receiving memantine |
Primary outcome
Genetics
Time frame: 6 months
The primary target of this study is the correlation of the distribution of genotypes and haplotypes of ABCB1 polymorphisms of patients with AD with Rhamnolipids (RLs) and Polysaccharides (LPSs) levels, as well as with steady-state levels of the respective drugs in the blood.
1 secondary outcome
Microbiome
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2022.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Alzheimer Disease, run by Aristotle University Of Thessaloniki at 1 site in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: status not confirmed, as of the sponsor's last update on 8 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Magda Tsolaki (0030 2310 2411 56, tsolakim1@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Genetics (time frame: 6 months). 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 8 Sep 2022.