Dementia AlzheimersDEM-BIOTANCT05943925
Dementias and Microbiota Composition: Is Possible to Revert the Dementia Symptoms Reverting the Microbiota Composition?
An observational study of Dementia Alzheimers and Dementia With Lewy Bodies, run by University Rovira i Virgili at 1 site in Spain.
Trial summary
Dementia is the major cause of disability and dependency among older adults worldwide affecting memory, cognitive abilities and behavior, interfering with one's ability to perform daily lives activities. Read more about this study
- Who is it for?
- Ages 60 years and olderHealthy volunteers can take part
- Conditions the study is for
- Dementia Alzheimers, Dementia With Lewy Bodies, Parkinson Disease Dementia
- What is being tested?
- Probiotic supplement
- How many people
- 240 participants
- Where
- 1 siteSpain
- Study dates
- 16 Apr 2021to 1 Feb 2025
- 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 60 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Clinic patients from hospitals and other diagnostic medical centers.
Who may be able to join
- Study 1, microbiota composition study- AD, PD, LBD, FTD-behavioral variant or MCI-amnesic
- diagnosed by the neurology service (or healthy subjects, without any of these diagnostics).
- more than 60 years
- Study 2-probiotic intervention,:
- AD diagnosed by the neurology service;
- more than 65 years.
Who cannot join
- Study 1, microbiota study:
- Comorbidity with other significant neurology disease,
- Infectious treatment with antibiotics in the previous 6 months prior to providing the stool sample,
- corticosteroid use,
- immunosuppressors or immunostimulants treatment,
- illnesses of the Gastro Intestinal tract,
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- large doses of commercial probiotics consumed (greater than or equal to 10 elevated to 8 colony forming unit per organisms per day).
- Study 2-probiotic intervention:
- Comorbidity with other significant neurology disease,
- Infectious treatment with antibiotics in the previous 6 months prior to providing the stool sample,
- corticosteroid use,
- immunosuppressors or immunostimulants treatment,
- illnesses of the GI tract,
- large doses of commercial probiotics consumed (greater than or equal to 10 elevated to 8 cfu per organisms per day).
Trial locations and contacts
1 site in 1 country.
Spain1 site, 1 recruiting
- Recruiting
Dr. Margarita Torrente
Tarragona, 43007
Margarita Torrente, Dr, +34 977558176, margarita.torrente@urv.cat
David Mateo, Predoc, +34 977759325, david.mateo@urv.cat
About this study
Dementia is the major cause of disability and dependency among older adults worldwide affecting memory, cognitive abilities and behavior, interfering with one's ability to perform daily lives activities. Although age is the strongest known risk factor for the onset of dementia, it is not a natural or inevitable consequence of aging. Dementia not only affects older people, since up to 9% of the cases appear before 65 years. The impact of dementia is highly important in financial terms also in human costs to countries, societies and individuals.
Dementia is an umbrella term for several diseases, being Alzheimer's disease (AD) the most common form, contributing to 60-70% of cases. Other major forms include Lewy bodies Dementias (LBDs) and frontotemporal dementia (FTD).
Read more
The role of the gastrointestinal microbiota in human brain development and function is an area of increasing interest and research. A large number of studies suggest that the gut microbiota can influence the brain, cognition and behavior of the patients, and also modulate brain plasticity, modifying brain chemistry via various mechanisms like neural, immune and endocrine Within these last two years some studies have showed differences in the microbiota of the AD patients from healthy controls. In this sense, increasing number of studies, most of them in animal models, support the notion that probiotics have significant benefit in maintaining homeostasis of the Central Nervous System. And recent studies try to replicate this finding in AD patients with controversial results.
The main objective of DEM-BIOTA project is to improve the knowledge of the relationship between microbiota and dementia. DEM-BIOTA will explore the microbiota differences between dementias: AD, LBDs, that includes: Parkinson disease dementia (PDD) and Lewy Body Dementia (LBD) and FTD-behavioral variant, also in Mild Cognitive Impairment (MCI) to study the progression; in our context (Mediterranean diet and lifestyle) and characterize them in relation to neurocognitive and neuropsychiatric symptoms as well as patient functionality (dependency level). Moreover, the capacity of a probiotic compound in reverting or improving neurocognitive and neuropsychiatric symptoms and patient functionality in a sample of AD patients will be also studied.
Read the detailed description
Hypothesis: Currently any other study to our knowledge has studied the relationship between gut microbiota and dementia symptoms in our country. Although there are few recent studies that have explored relations between microbiota and dementia, they were conducted in Japan or USA. Taken into account the important factor of diet and lifestyle in microbiota composition and the differences between these countries (Japan and USA) and Mediterranean diet and lifestyle, it was the need of a relational study in our context. The hypothesis is that although it will be different microbiota between healthy and demented subjects, the microbiota composition of healthy subjects in Mediterranean context could significant differ from the above-mentioned studies.
In the few studies already conducted, the patients included were diagnosticated of AD or it were included patients from all type of dementias. Even though AD is the most common type of dementia, there are more types of dementias that should be considered differentially as the features are significantly different. Given the diversity through the symptoms across dementias, a characterization of the gut microbiota of different types of dementia will be described, specifically, AD, LBDs: LBD and PDD separately, and FTD-behavioral variant. Furthermore, MCI subjects will be also studied in order to explore the microbiota changes before the onset of dementia (taking into account the high percentage of MCI that progress to dementia). These studies could reveal a risk factor compositional microbiota to develop dementia. The hypothesis is that microbiota will differ through different dementias and could be related to the feature symptoms of each one, being MCI subjects between healthy and dementia patients, in terms of microbiota composition.
As pointed out in the introduction, preclinical research shows that probiotics may improve cognitive performances in animal models with impaired cognition. However, data about the effects of probiotics on cognitive performance or psychopathological symptoms in humans are scarce and controversial. This lack of agreement could due to the differences in the population studied (young adults, elderly, healthy and clinic population, neurologic and psychiatric patients), the measures (different mood scales and different cognitive assessments), the probiotic compositions and the duration of treatment (from 3 weeks to 12 weeks). Considering the lack of knowledge about the probiotics potential treating dementia symptoms, dementia AD patients will be treated with a probiotic compound (a probiotic mixture already successful in improving cognitive impairment in AD patients, but only assessed by a cognitive screening and with no analysis of microbiota). The study will be conducted in an elderly group affected from AD, with a broad type of neuropsychological, neuropsychiatric and functional measures, and microbiota characterization at 12 and 24 weeks of treatment. An improvement of dementia symptoms due to probiotic consumption is expected, not only neuropsychological but also at a neuropsychiatric and functional level and these changes will be related to the changes of microbiota composition.
General objective: The main objective of DEM-BIOTA is to confirm the relationship between microbiota and dementia in our model of diet and lifestyle, improving the knowledge of the relationship between microbiota and dementias. This means to explore the possible differences between dementias in relation to microbiota in our context (Mediterranean diet and style of life) and characterize them in relation to neurocognitive and neuropsychiatric symptoms as well as patient functionality (dependency level). Moreover, the capacity of a probiotic compound in reverting or improving neurocognitive and neuropsychiatric symptoms and patient functionality will be studied.
This objective will be achieved through a multidisciplinary study considering microbiota composition and deep study of the dementia symptoms taking into account the personal characteristics of each patient. The final issue is to draw a relational map about the microbiota composition and dementia symptoms and the identification of the microbiota strains that are a risk factor of produce a deficit in metabolites. The project proposes to finally study how can a probiotic mixture improve AD symptoms, and study in deep the microbiota composition changes along with the changes (or not) of dementia symptoms.
This main objective will be carried out by combining our previous knowledge, partly of the collaboration with European Union partners, with data provided by literature on international studies on human population.
The aim match with the activities addressed in 1st Challenge identified in the Spanish Strategy for R+D+I Targeted to Societal Challenges "Health, Geographical change and Well-being": 1.1.2. Understanding disease; 1.2.1. Development of effective prevention and detection programs and improvement of disease propensity assessment.
1.3. SPECIFIC OBJECTIVES
- - Protocol revision and preparation. Revision of the all tests and scales, writing down all the protocols, alignment the study protocols with the hospitals' procedures, timetables, sample collection protocols, etc.
- - Study the microbiota composition (from stool samples of the patients) of AD patients in our context (Mediterranean lifestyle). Describe the microbiota composition from AD patients in relation with their healthy controls. To what extent does it differ from their controls and from the AD patient's composition of other countries?
- - Study microbiota composition differences (from stool samples of the patients) between some of the most known dementias: AD, PDD, LBD, FTD-behavioral variant Describe and compare microbiota composition between some of the most known dementias: AD, PDD, LBD, FTD-behavioral variant. Describe and compare microbiota composition between MCI patients and AD patients. Describe and compare microbiota composition between MCI patients and PDD, LBD, FTD-behavioral variant patients. Are there any relations between the microbiota composition of all experimental groups with neuropsychological, neuropsychiatric and functional characteristics present in these dementias and in these patients? All these relations could be modulated by life stressors and diet (adherence to Mediterranean diet)?
- - Study the effects of a probiotic compound in AD patients. In relation to AD symptoms: neuropsychological, neuropsychiatric and functional In relation to microbiota composition (analyzed from the stool samples of the patients) Until what extend and how the microbiota composition explains the AD symptoms? Can this probiotic compound improve the symptoms and is in general a good treatment/complement to the nowadays treatment?
- - Dissemination and formation. Dissemination of results at scientific (open access journals, congresses and other national and international meetings) and social level disclosure (newspapers, research group web, webs of the hospitals and Alzheimer association, conferences to general public, radio, television, etc.), as well as formation to patients, professionals and general public.
- Conditions
- Dementia Alzheimers, Dementia With Lewy Bodies, Parkinson Disease Dementia, Dementia Frontotemporal, Mild Cognitive Impairment
- Being tested
- No intervention, Probiotic supplement
- Keywords
- cognitive status, functional status, neuropsychiatric status, microbiota
- Medical subject headings
- Alzheimer Disease, Lewy Body Disease, Pick Disease of the Brain, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No interventionOther
no intervention
Probiotic supplementDietary supplement
A total of 60 Alzheimer Disease (AD) patients will be recruited, 30 will ingest the probiotic mixture and 30 will ingest placebo (randomized assignment to the groups will be done). The experimental group will take the probiotic ingest daily: Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, and Lactobacillus fermentum (2 × 109 colony forming units (CFU)/g of each). This mixture of bacteria has been showed to have positive results with 12 weeks treatment.
| Study group | Role | What they receive |
|---|---|---|
| Healthy control group | The criteria for the recruitment will be:
Inclusion criteria: more than 60 years. Exclusion criteria: Significant neurology disease diagnosed, infectious treatment with antibiotics in the previous 6 months prior to providing the stool sample, corticosteroid use, immunosuppressors or immunostimulants treatment, illnesses of the gastrointestinal (GI) tract, large doses of commercial probiotics consumed (greater than or equal to 108 colony forming units (cfu) per organisms per day).
This control group were recruited from relatives of the patients enrolled or general population and interviewed at the hospital (relatives, University or their homes).
Neuropsychological, functional and neuropsychiatric assessment and stool sample. Receives: Other: No intervention | |
| Alzheimer Disease (AD) | The criteria for the recruitment will be:
Inclusion criteria: Alzheimer Disease (AD) diagnosed by the neurology service; more than 60 years.
Exclusion criteria: Comorbidity with other significant neurology disease, infectious treatment with antibiotics in the previous 6 months prior to providing the stool sample, corticosteroid use, immunosuppressors or immunostimulants treatment, illnesses of the GI tract, large doses of commercial probiotics consumed (greater than or equal to 108 colony forming units (cfu) per organisms per day).
Neuropsychological, functional and neuropsychiatric assessment and stool sample. Receives: Other: No intervention | |
| Mild Cognitive Impairment (MCI)- amnesic | The criteria for the recruitment will be:
Inclusion criteria: Mild Cognitive Impairment (MCI) amnesic, diagnosed by the neurology service; more than 60 years.
Exclusion criteria: Comorbidity with other significant neurology disease, infectious treatment with antibiotics in the previous 6 months prior to providing the stool sample, corticosteroid use, immunosuppressors or immunostimulants treatment, illnesses of the gastrointestinal (GI) tract, large doses of commercial probiotics consumed (greater than or equal to 108 colony forming units (cfu) per organisms per day).
Neuropsychological, functional and neuropsychiatric assessment and stool sample. Receives: Other: No intervention | |
| Parkinson Disease Dementia (PDD) | The criteria for the recruitment will be:
Inclusion criteria: Parkinson Disease Dementia (PDD) diagnosed by the neurology service; more than 60 years.
Exclusion criteria: Comorbidity with other significant neurology disease, infectious treatment with antibiotics in the previous 6 months prior to providing the stool sample, corticosteroid use, immunosuppressors or immunostimulants treatment, illnesses of the gastrointestinal (GI) tract, large doses of commercial probiotics consumed (greater than or equal to 108 colony forming units (cfu) per organisms per day).
Neuropsychological, functional and neuropsychiatric assessment and stool sample. Receives: Other: No intervention | |
| Lewy bodies dementia (LBD) | The criteria for the recruitment will be:
Inclusion criteria: Lewy Body Dementia (LBD) diagnosed by the neurology service; more than 60 years.
Exclusion criteria: Comorbidity with other significant neurology disease, infectious treatment with antibiotics in the previous 6 months prior to providing the stool sample, corticosteroid use, immunosuppressors or immunostimulants treatment, illnesses of the gastrointestinal (GI) tract, large doses of commercial probiotics consumed (greater than or equal to 108 colony forming units (cfu) per organisms per day).
Neuropsychological, functional and neuropsychiatric assessment and stool sample. Receives: Other: No intervention | |
| Frontotemporal Dementia (FTD)-behavioral variant | The criteria for the recruitment will be:
Inclusion criteria: Frontotemporal Dementia (FTD)-behavioral variant diagnosed by the neurology service; more than 60 years.
Exclusion criteria: Comorbidity with other significant neurology disease, infectious treatment with antibiotics in the previous 6 months prior to providing the stool sample, corticosteroid use, immunosuppressors or immunostimulants treatment, illnesses of the gastrointestinal (GI) tract, large doses of commercial probiotics consumed (greater than or equal to 108 colony forming units (cfu) per organisms per day).
Neuropsychological, functional and neuropsychiatric assessment and stool sample. Receives: Other: No intervention | |
| Alzheimer disease (AD)-control | Inclusion criteria: Alzheimer Disease (AD) diagnosed by the neurology service; more than 65 years. Exclusion criteria: Comorbidity with other significant neurology disease, infectious treatment with antibiotics in the previous 6 months prior to providing the stool sample, corticosteroid use, immunosuppressors or immunostimulants treatment, illnesses of the gastrointestinal (GI) tract, large doses of commercial probiotics consumed (greater than or equal to 108 colony forming units (cfu) per organisms per day).
Neuropsychological, functional and neuropsychiatric assessment and stool sample at basal, 12 weeks and 24 weeks. Receives: Dietary Supplement: Probiotic supplement | |
| Alzheimer disease (AD)-probiotic | Inclusion criteria: Alzheimer Disease (AD) diagnosed by the neurology service; more than 65 years. Exclusion criteria: Comorbidity with other significant neurology disease, infectious treatment with antibiotics in the previous 6 months prior to providing the stool sample, corticosteroid use, immunosuppressors or immunostimulants treatment, illnesses of the gastrointestinal (GI) tract, large doses of commercial probiotics consumed (greater than or equal to 108 colony forming units (cfu) per organisms per day).
Neuropsychological, functional and neuropsychiatric assessment and stool sample at basal, 12 weeks and 24 weeks. Receives: Dietary Supplement: Probiotic supplement |
What is being measured
The primary outcome is the main question the study is designed to answer.
Shotgun sequencing metagenomics analysis (NextSeq2000)
Gut microbiome was analysed using a shotgun metagenomic approach. DNA was extracted from samples using the DNA Preparation with Tagmentation kit, according to manufacturer protocols (Illumina, California, USA, catalog no. 20018705). Sequencing libraries concentration was determined by Qubit 4.0 fluorometer and Qubit dsDNA High Sensivity Assay Kit (Thermo Fisher Scientific, Massachusetts, USA). Sequencing libraries length was checked by Agilent TapeStation and Agilent High Sensitivity DNA kit (Agilent Technologies, California, USA). Sequencing libraries with concentration below 750 per Molar and length out of 400-600 bp range were discarded. Final sequencing libraries were mixed at 750 bp and sequenced using the NextSeq 2000 sequencing system (Illumina, California, USA) as 2x150-bp paired-end reads. Samples below 7,5 million reads were discarded. Shotgun metagenomic reads were profiled for microbial species relative abundances by mapping them to several databases with Kraken2.
Measured: Baseline for all the group subjects subjects in microbiota composition study. Baseline, change from baseline at 12 weeks and change from baseline at 24 weeks for Alzheimer Disease (AD) patients in the probiotic study.
Neuropsychology assessment: Mini Mental State Examination (MMSE)
Mini Mental State Examination (MMSE), screening test for cognitive deterioration.
At Baseline for no intervention study, study 1.
For the probiotic study, study 2, at baseline, change at 12 weeks and change at 24 weeks
Measured: Baseline for all the group subjects subjects in microbiota composition study. Baseline, change from baseline at 12 weeks and change from baseline at 24 weeks for AD patients in the probiotic study.
Neuropsychology assessment: Global Deterioration Scale-Functional Assessment Staging (GDS-FAST)
Global Deterioration Scale-Functional Assessment Staging (GDS-FAST)
At Baseline for no intervention study, study 1.
For the probiotic study, study 2, at baseline, change from baseline at 12 weeks and change from baseline at 24 weeks.
Measured: Baseline for all the group subjects subjects in microbiota composition study. Baseline, change from baseline at 12 weeks and change from baseline at 24 weeks for AD patients in the probiotic study.
Neuropsychology assessment: Clinical Dementia Rating (CDR)
Clinical Dementia Rating (CDR) score.
At Baseline for no intervention study, study 1.
For the probiotic study, study 2, at baseline, change from the baseline at 12 weeks and change from baseline at 24 weeks.
Measured: Baseline for all the group subjects subjects in microbiota composition study. Baseline, change from baseline at 12 weeks and change from baseline at 24 weeks for AD patients in the probiotic study.
Neuropsychology assessment: Memory Impairment Screen (MIS)
Memory Impairment Screen (MIS). Screening test for memory impairment.
At Baseline for no intervention study, study 1.
Measured: Baseline for all the group subjects subjects in microbiota composition study.
Neuropsychology assessment: Categorical Recall Test (Barcelona-2 Test)
Categorical Recall Test (Barcelona-2 Test), semantic and phonemic fluency tests
At Baseline for no intervention study, study 1.
Measured: Baseline for all the group subjects subjects in microbiota composition study.
Neuropsychology assessment: Orientation
Orientation in Time, Space and Person (Barcelona-2 Test)
At Baseline for no intervention study, study 1.
Measured: Baseline for all the group subjects subjects in microbiota composition study.
Neuropsychology assessment: Free and Cue Selective Reminding Test (FCSRT)
Free and Cue Selective Reminding Test (FCSRT). Long and short Memory assessment test.
At Baseline for no intervention study, study 1.
Measured: Baseline for all the group subjects subjects in microbiota composition study.
Neuropsychology assessment: Trial Making Test (TMT) A and B
TMT A and B. Measures visuospatial, attention and executive functions.
At Baseline for no intervention study, study 1.
Measured: Baseline for all the group subjects subjects in microbiota composition study.
Neuropsychology assessment: Boston Abbreviated Naming Test
Boston Abbreviated Naming Test
At Baseline for no intervention study, study 1.
Measured: Baseline for all the group subjects subjects in microbiota composition study.
Neuropsychology assessment: Verbal span
Verbal Span (Barcelona-2 Test), that assesses attentional span and control/working memory.
At Baseline for no intervention study, study 1.
Measured: Baseline for all the group subjects subjects in microbiota composition study.
Neuropsychology assessment: Clock test
Clock Test, screening test for detecting cognitive impairment
At Baseline for no intervention study, study 1.
Measured: Baseline for all the group subjects subjects in microbiota composition study.
Neuropsychology assessment: Frontal Assessment Battery (FAB)
Frontal Assessment Battery (FAB), that assesses impairments related to frontal lobe function.
At Baseline for no intervention study, study 1.
Measured: Baseline for all the group subjects subjects in microbiota composition study.
Neuropsychology assessment: Simple and semi complex constructive praxis (Barcelona-2 Test)
Simple and semi complex constructive praxis (Barcelona-2 Test)
At Baseline for no intervention study, study 1.
Measured: Baseline for all the group subjects subjects in microbiota composition study.
Neuropsychology assessment: Abbreviated Barcelona-2 Test
Abbreviated Barcelona-2 Test. Abbreviated neuropsychological battery already normalised in Spanish populations.
Only for the probiotic study, study 2, at baseline, change from baseline at 12 weeks and change from baseline at 24 weeks.
Measured: Baseline, change from baseline at 12 weeks and change from baseline at 24 weeks for AD patients in the probiotic study.
Neuropsychiatric assessment: Golberg Anxiety and Depression Scale
Golberg Anxiety and Depression Scale (more punctuation, more anxiety or depression symptoms) At Baseline for no intervention study
For the probiotic study:
At baseline, change from baseline at 12 weeks and change from baseline at 24 weeks.
Measured: Baseline for all the group subjects subjects in microbiota composition study. Baseline, change from baseline at 12 weeks and change from baseline at 24 weeks for AD patients in the probiotic study.
Neuropsychiatric assessment: Neuropsychiatric Symptoms (Barcelona-2 Test)
For microbiota composition study, the following tests will be assessed:
Neuropsychiatric Symptoms (Barcelona-2 Test), (more punctuation, more neuropsychiatric symptoms) At Baseline for no intervention study
For the probiotic study:
At baseline, change from baseline at 12 weeks and change from baseline 24 weeks.
Measured: Baseline for all the group subjects subjects in microbiota composition study. Baseline, change from baseline at 12 weeks and change from baseline at 24 weeks for AD patients in the probiotic study.
Functional assessment
For microbiota composition study, the following tests will be assessed:
Activities of Daily Living (ADL) (Barcelona-2 Test), (more punctuation, more dependent; punctuation total scale 0-100, Instrumental activities 0-60 + Basic activities 0-40) At Baseline for no intervention study
For the probiotic study:
At baseline, change from baseline at 12 weeks and change from baseline at 24 weeks, the following tests will be assessed:
Activities of Daily Living ADL (Barcelona-2 Test), (more punctuation, more dependent; punctuation total scale 0-100, Instrumental activities 0-60 + Basic activities 0-40)
Measured: Baseline for all the group subjects subjects in microbiota composition study. Baseline, change from baseline at 12 weeks and change from baseline at 24 weeks for AD patients in the probiotic study.
Secondary outcomes (3)
Assessment of stress events
For microbiota composition study, the following tests will be assessed:
Life Events Questionnaire, adapted from the Predimed-Plus study, which provides information on successfully overcome stressful events that could affect and modify the main variables under study (more punctuation, more stress).
At Baseline for no intervention study
For the probiotic study:
At baseline, change from baseline at 12 weeks and change from baseline at24 weeks, the following tests will be assessed:
Life Events Questionnaire, adapted from the Predimed-Plus study, which provides information on successfully overcome stressful events that could affect and modify the main variables under study (more punctuation, more stress).
Measured: Baseline for all the group subjects subjects in microbiota composition study. Baseline, change from baseline at 12 weeks and change from baseline at 24 weeks for AD patients in the probiotic study.
Mediterranean lifestyle assessment
For microbiota composition study, the following tests will be assessed:
Mediterranean lifestyle index interview (MEDLIFE), which provides information on how the patient follows the Mediterranean diet and lifestyle habits, more punctuation, more adhered to Mediterranean lifestyle.
At Baseline for no intervention study
For the probiotic study:
At baseline, change from baseline at 12 weeks and change from baseline at24 weeks, the following tests will be assessed:
Mediterranean lifestyle index interview (MEDLIFE), which provides information on how the patient follows the Mediterranean diet and lifestyle habits, more punctuation, more adhered to Mediterranean lifestyle.
Measured: Baseline for all the group subjects subjects in microbiota composition study. Baseline, change from baseline at 12 weeks and change from baseline at 24 weeks for AD patients in the probiotic study.
Cognitive reserve assessment
For microbiota composition study, the following tests will be assessed:
Cognitive reserve scale (more punctuation more cognitive reserve, score 0-25) At Baseline for no intervention study
For the probiotic study:
At baseline, change from baseline at 12 weeks and change from baseline at 24 weeks, the following tests will be assessed:
Cognitive reserve scale (more punctuation more cognitive reserve, score 0-25)
Measured: Baseline for all the group subjects subjects in microbiota composition study. Baseline, change from baseline at 12 weeks and change from baseline at 24 weeks for AD patients in the probiotic study.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2023
- Study start16 Apr 2021
- Primary completion31 Jan 2025 (estimated)
- Study completion1 Feb 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (23)Papers the sponsor has linked to this study.
- Other trials for Dementia AlzheimersStudies 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
- Case-control
- Time perspective
- Other
- Enrolment
- 240 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Rovira i Virgili
- Sponsor type
- University, hospital or other
- Collaborators
- Ministerio de Ciencia e Innovación, Spain
- Responsible party
- Principal investigator, Margarita Torrente, University Rovira i Virgili
- Investigators
- Margarita Torrente, Dr, Principal investigator, University Rovira i Virgili
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05943925
- Sponsor's protocol ID
- PID2019-103888RB-I00
- Acronym
- DEM-BIOTA
- Status last verified
- Jun 2023
- First submitted
- 26 Apr 2023
- Last updated
- 13 Jul 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: It is not decided yet.
Publications
Cabrera C, Vicens P, Torrente M. Modifiable Risk Factors for Dementia: The Role of Gut Microbiota. Curr Alzheimer Res. 2021;18(13):993-1009. doi: 10.2174/1567205018666211215152411.
PubMed 34911422Agahi A, Hamidi GA, Daneshvar R, Hamdieh M, Soheili M, Alinaghipour A, Esmaeili Taba SM, Salami M. Does Severity of Alzheimer's Disease Contribute to Its Responsiveness to Modifying Gut Microbiota? A Double Blind Clinical Trial. Front Neurol. 2018 Aug 15;9:662. doi: 10.3389/fneur.2018.00662. eCollection 2018.
PubMed 30158897Akbari E, Asemi Z, Daneshvar Kakhaki R, Bahmani F, Kouchaki E, Tamtaji OR, Hamidi GA, Salami M. Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial. Front Aging Neurosci. 2016 Nov 10;8:256. doi: 10.3389/fnagi.2016.00256. eCollection 2016.
PubMed 27891089Benton D, Williams C, Brown A. Impact of consuming a milk drink containing a probiotic on mood and cognition. Eur J Clin Nutr. 2007 Mar;61(3):355-61. doi: 10.1038/sj.ejcn.1602546. Epub 2006 Dec 6.
PubMed 17151594Davari S, Talaei SA, Alaei H, Salami M. Probiotics treatment improves diabetes-induced impairment of synaptic activity and cognitive function: behavioral and electrophysiological proofs for microbiome-gut-brain axis. Neuroscience. 2013 Jun 14;240:287-96. doi: 10.1016/j.neuroscience.2013.02.055. Epub 2013 Mar 7.
PubMed 23500100Kelly JR, Allen AP, Temko A, Hutch W, Kennedy PJ, Farid N, Murphy E, Boylan G, Bienenstock J, Cryan JF, Clarke G, Dinan TG. Lost in translation? The potential psychobiotic Lactobacillus rhamnosus (JB-1) fails to modulate stress or cognitive performance in healthy male subjects. Brain Behav Immun. 2017 Mar;61:50-59. doi: 10.1016/j.bbi.2016.11.018. Epub 2016 Nov 16.
PubMed 27865949Messaoudi M, Lalonde R, Violle N, Javelot H, Desor D, Nejdi A, Bisson JF, Rougeot C, Pichelin M, Cazaubiel M, Cazaubiel JM. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br J Nutr. 2011 Mar;105(5):755-64. doi: 10.1017/S0007114510004319. Epub 2010 Oct 26.
PubMed 20974015Saji N, Niida S, Murotani K, Hisada T, Tsuduki T, Sugimoto T, Kimura A, Toba K, Sakurai T. Analysis of the relationship between the gut microbiome and dementia: a cross-sectional study conducted in Japan. Sci Rep. 2019 Jan 30;9(1):1008. doi: 10.1038/s41598-018-38218-7.
PubMed 30700769Tillisch K, Labus J, Kilpatrick L, Jiang Z, Stains J, Ebrat B, Guyonnet D, Legrain-Raspaud S, Trotin B, Naliboff B, Mayer EA. Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology. 2013 Jun;144(7):1394-401, 1401.e1-4. doi: 10.1053/j.gastro.2013.02.043. Epub 2013 Mar 6.
PubMed 23474283Vogt NM, Kerby RL, Dill-McFarland KA, Harding SJ, Merluzzi AP, Johnson SC, Carlsson CM, Asthana S, Zetterberg H, Blennow K, Bendlin BB, Rey FE. Gut microbiome alterations in Alzheimer's disease. Sci Rep. 2017 Oct 19;7(1):13537. doi: 10.1038/s41598-017-13601-y.
PubMed 29051531Soldevila-Domenech N, Forcano L, Vintro-Alcaraz C, Cuenca-Royo A, Pinto X, Jimenez-Murcia S, Garcia-Gavilan JF, Nishi SK, Babio N, Gomis-Gonzalez M, Corella D, Sorli JV, Fernandez-Carrion R, Martinez-Gonzalez MA, Marti A, Salas-Salvado J, Castaner O, Fernandez-Aranda F, Torre R. Interplay between cognition and weight reduction in individuals following a Mediterranean Diet: Three-year follow-up of the PREDIMED-Plus trial. Clin Nutr. 2021 Sep;40(9):5221-5237. doi: 10.1016/j.clnu.2021.07.020. Epub 2021 Aug 5.
PubMed 34474192Buschke H. Cued recall in amnesia. J Clin Neuropsychol. 1984 Nov;6(4):433-40. doi: 10.1080/01688638408401233.
PubMed 6501581Buschke H, Kuslansky G, Katz M, Stewart WF, Sliwinski MJ, Eckholdt HM, Lipton RB. Screening for dementia with the memory impairment screen. Neurology. 1999 Jan 15;52(2):231-8. doi: 10.1212/wnl.52.2.231.
PubMed 9932936Dubois B, Slachevsky A, Litvan I, Pillon B. The FAB: a Frontal Assessment Battery at bedside. Neurology. 2000 Dec 12;55(11):1621-6. doi: 10.1212/wnl.55.11.1621.
PubMed 11113214Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975 Nov;12(3):189-98. doi: 10.1016/0022-3956(75)90026-6. No abstract available.
PubMed 1202204
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dementias and Microbiota Composition: Is Possible to Revert the Dementia Symptoms Reverting the Microbiota Composition?
- ClinicalTrials.gov ID
- NCT05943925
- Acronym / sponsor ID
- DEM-BIOTA / PID2019-103888RB-I00
- Conditions
- Dementia Alzheimers, Dementia With Lewy Bodies, Parkinson Disease Dementia, Dementia Frontotemporal, Mild Cognitive Impairment
- Keywords
- cognitive status, functional status, neuropsychiatric status, microbiota
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 240 participants (estimated)
- Lead sponsor
- University Rovira i VirgiliUniversity, hospital or other
- Collaborators
- Ministerio de Ciencia e Innovación, Spain
- Study start
- 16 Apr 2021 (actual)
- Primary completion
- 31 Jan 2025 (estimated)
- Study completion
- 1 Feb 2025 (estimated)
- First posted
- 13 Jul 2023 (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.
Dementia is the major cause of disability and dependency among older adults worldwide affecting memory, cognitive abilities and behavior, interfering with one's ability to perform daily lives activities. Although age is the strongest known risk factor for the onset of dementia, it is not a natural or inevitable consequence of aging. Dementia not only affects older people, since up to 9% of the cases appear before 65 years. The impact of dementia is highly important in financial terms also in human costs to countries, societies and individuals.
Dementia is an umbrella term for several diseases, being Alzheimer's disease (AD) the most common form, contributing to 60-70% of cases. Other major forms include Lewy bodies Dementias (LBDs) and frontotemporal dementia (FTD).
The role of the gastrointestinal microbiota in human brain development and function is an area of increasing interest and research. A large number of studies suggest that the gut microbiota can influence the brain, cognition and behavior of the patients, and also modulate brain plasticity, modifying brain chemistry via various mechanisms like neural, immune and endocrine Within these last two years some studies have showed differences in the microbiota of the AD patients from healthy controls. In this sense, increasing number of studies, most of them in animal models, support the notion that probiotics have significant benefit in maintaining homeostasis of the Central Nervous System. And recent studies try to replicate this finding in AD patients with controversial results.
The main objective of DEM-BIOTA project is to improve the knowledge of the relationship between microbiota and dementia. DEM-BIOTA will explore the microbiota differences between dementias: AD, LBDs, that includes: Parkinson disease dementia (PDD) and Lewy Body Dementia (LBD) and FTD-behavioral variant, also in Mild Cognitive Impairment (MCI) to study the progression; in our context (Mediterranean diet and lifestyle) and characterize them in relation to neurocognitive and neuropsychiatric symptoms as well as patient functionality (dependency level). Moreover, the capacity of a probiotic compound in reverting or improving neurocognitive and neuropsychiatric symptoms and patient functionality in a sample of AD patients will be also studied.
Detailed description
Hypothesis: Currently any other study to our knowledge has studied the relationship between gut microbiota and dementia symptoms in our country. Although there are few recent studies that have explored relations between microbiota and dementia, they were conducted in Japan or USA. Taken into account the important factor of diet and lifestyle in microbiota composition and the differences between these countries (Japan and USA) and Mediterranean diet and lifestyle, it was the need of a relational study in our context. The hypothesis is that although it will be different microbiota between healthy and demented subjects, the microbiota composition of healthy subjects in Mediterranean context could significant differ from the above-mentioned studies.
In the few studies already conducted, the patients included were diagnosticated of AD or it were included patients from all type of dementias. Even though AD is the most common type of dementia, there are more types of dementias that should be considered differentially as the features are significantly different. Given the diversity through the symptoms across dementias, a characterization of the gut microbiota of different types of dementia will be described, specifically, AD, LBDs: LBD and PDD separately, and FTD-behavioral variant. Furthermore, MCI subjects will be also studied in order to explore the microbiota changes before the onset of dementia (taking into account the high percentage of MCI that progress to dementia). These studies could reveal a risk factor compositional microbiota to develop dementia. The hypothesis is that microbiota will differ through different dementias and could be related to the feature symptoms of each one, being MCI subjects between healthy and dementia patients, in terms of microbiota composition.
As pointed out in the introduction, preclinical research shows that probiotics may improve cognitive performances in animal models with impaired cognition. However, data about the effects of probiotics on cognitive performance or psychopathological symptoms in humans are scarce and controversial. This lack of agreement could due to the differences in the population studied (young adults, elderly, healthy and clinic population, neurologic and psychiatric patients), the measures (different mood scales and different cognitive assessments), the probiotic compositions and the duration of treatment (from 3 weeks to 12 weeks). Considering the lack of knowledge about the probiotics potential treating dementia symptoms, dementia AD patients will be treated with a probiotic compound (a probiotic mixture already successful in improving cognitive impairment in AD patients, but only assessed by a cognitive screening and with no analysis of microbiota). The study will be conducted in an elderly group affected from AD, with a broad type of neuropsychological, neuropsychiatric and functional measures, and microbiota characterization at 12 and 24 weeks of treatment. An improvement of dementia symptoms due to probiotic consumption is expected, not only neuropsychological but also at a neuropsychiatric and functional level and these changes will be related to the changes of microbiota composition.
General objective: The main objective of DEM-BIOTA is to confirm the relationship between microbiota and dementia in our model of diet and lifestyle, improving the knowledge of the relationship between microbiota and dementias. This means to explore the possible differences between dementias in relation to microbiota in our context (Mediterranean diet and style of life) and characterize them in relation to neurocognitive and neuropsychiatric symptoms as well as patient functionality (dependency level). Moreover, the capacity of a probiotic compound in reverting or improving neurocognitive and neuropsychiatric symptoms and patient functionality will be studied.
This objective will be achieved through a multidisciplinary study considering microbiota composition and deep study of the dementia symptoms taking into account the personal characteristics of each patient. The final issue is to draw a relational map about the microbiota composition and dementia symptoms and the identification of the microbiota strains that are a risk factor of produce a deficit in metabolites. The project proposes to finally study how can a probiotic mixture improve AD symptoms, and study in deep the microbiota composition changes along with the changes (or not) of dementia symptoms.
This main objective will be carried out by combining our previous knowledge, partly of the collaboration with European Union partners, with data provided by literature on international studies on human population.
The aim match with the activities addressed in 1st Challenge identified in the Spanish Strategy for R+D+I Targeted to Societal Challenges "Health, Geographical change and Well-being": 1.1.2. Understanding disease; 1.2.1. Development of effective prevention and detection programs and improvement of disease propensity assessment.
1.3. SPECIFIC OBJECTIVES
- - Protocol revision and preparation. Revision of the all tests and scales, writing down all the protocols, alignment the study protocols with the hospitals' procedures, timetables, sample collection protocols, etc.
- - Study the microbiota composition (from stool samples of the patients) of AD patients in our context (Mediterranean lifestyle). Describe the microbiota composition from AD patients in relation with their healthy controls. To what extent does it differ from their controls and from the AD patient's composition of other countries?
- - Study microbiota composition differences (from stool samples of the patients) between some of the most known dementias: AD, PDD, LBD, FTD-behavioral variant Describe and compare microbiota composition between some of the most known dementias: AD, PDD, LBD, FTD-behavioral variant. Describe and compare microbiota composition between MCI patients and AD patients. Describe and compare microbiota composition between MCI patients and PDD, LBD, FTD-behavioral variant patients. Are there any relations between the microbiota composition of all experimental groups with neuropsychological, neuropsychiatric and functional characteristics present in these dementias and in these patients? All these relations could be modulated by life stressors and diet (adherence to Mediterranean diet)?
- - Study the effects of a probiotic compound in AD patients. In relation to AD symptoms: neuropsychological, neuropsychiatric and functional In relation to microbiota composition (analyzed from the stool samples of the patients) Until what extend and how the microbiota composition explains the AD symptoms? Can this probiotic compound improve the symptoms and is in general a good treatment/complement to the nowadays treatment?
- - Dissemination and formation. Dissemination of results at scientific (open access journals, congresses and other national and international meetings) and social level disclosure (newspapers, research group web, webs of the hospitals and Alzheimer association, conferences to general public, radio, television, etc.), as well as formation to patients, professionals and general public.
Study design
- Observational model
- Case-control
- Time perspective
- Other
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Healthy control group | – | Other: No interventionThe criteria for the recruitment will be: Inclusion criteria: more than 60 years. Exclusion criteria: Significant neurology disease diagnosed, infectious treatment with antibiotics in the previous 6 months prior to providing the stool sample, corticosteroid use, immunosuppressors or immunostimulants treatment, illnesses of the gastrointestinal (GI) tract, large doses of commercial probiotics consumed (greater than or equal to 108 colony forming units (cfu) per organisms per day). This control group were recruited from relatives of the patients enrolled or general population and interviewed at the hospital (relatives, University or their homes). Neuropsychological, functional and neuropsychiatric assessment and stool sample. |
| Alzheimer Disease (AD) | – | Other: No interventionThe criteria for the recruitment will be: Inclusion criteria: Alzheimer Disease (AD) diagnosed by the neurology service; more than 60 years. Exclusion criteria: Comorbidity with other significant neurology disease, infectious treatment with antibiotics in the previous 6 months prior to providing the stool sample, corticosteroid use, immunosuppressors or immunostimulants treatment, illnesses of the GI tract, large doses of commercial probiotics consumed (greater than or equal to 108 colony forming units (cfu) per organisms per day). Neuropsychological, functional and neuropsychiatric assessment and stool sample. |
| Mild Cognitive Impairment (MCI)- amnesic | – | Other: No interventionThe criteria for the recruitment will be: Inclusion criteria: Mild Cognitive Impairment (MCI) amnesic, diagnosed by the neurology service; more than 60 years. Exclusion criteria: Comorbidity with other significant neurology disease, infectious treatment with antibiotics in the previous 6 months prior to providing the stool sample, corticosteroid use, immunosuppressors or immunostimulants treatment, illnesses of the gastrointestinal (GI) tract, large doses of commercial probiotics consumed (greater than or equal to 108 colony forming units (cfu) per organisms per day). Neuropsychological, functional and neuropsychiatric assessment and stool sample. |
| Parkinson Disease Dementia (PDD) | – | Other: No interventionThe criteria for the recruitment will be: Inclusion criteria: Parkinson Disease Dementia (PDD) diagnosed by the neurology service; more than 60 years. Exclusion criteria: Comorbidity with other significant neurology disease, infectious treatment with antibiotics in the previous 6 months prior to providing the stool sample, corticosteroid use, immunosuppressors or immunostimulants treatment, illnesses of the gastrointestinal (GI) tract, large doses of commercial probiotics consumed (greater than or equal to 108 colony forming units (cfu) per organisms per day). Neuropsychological, functional and neuropsychiatric assessment and stool sample. |
| Lewy bodies dementia (LBD) | – | Other: No interventionThe criteria for the recruitment will be: Inclusion criteria: Lewy Body Dementia (LBD) diagnosed by the neurology service; more than 60 years. Exclusion criteria: Comorbidity with other significant neurology disease, infectious treatment with antibiotics in the previous 6 months prior to providing the stool sample, corticosteroid use, immunosuppressors or immunostimulants treatment, illnesses of the gastrointestinal (GI) tract, large doses of commercial probiotics consumed (greater than or equal to 108 colony forming units (cfu) per organisms per day). Neuropsychological, functional and neuropsychiatric assessment and stool sample. |
| Frontotemporal Dementia (FTD)-behavioral variant | – | Other: No interventionThe criteria for the recruitment will be: Inclusion criteria: Frontotemporal Dementia (FTD)-behavioral variant diagnosed by the neurology service; more than 60 years. Exclusion criteria: Comorbidity with other significant neurology disease, infectious treatment with antibiotics in the previous 6 months prior to providing the stool sample, corticosteroid use, immunosuppressors or immunostimulants treatment, illnesses of the gastrointestinal (GI) tract, large doses of commercial probiotics consumed (greater than or equal to 108 colony forming units (cfu) per organisms per day). Neuropsychological, functional and neuropsychiatric assessment and stool sample. |
| Alzheimer disease (AD)-control | – | Dietary Supplement: Probiotic supplementInclusion criteria: Alzheimer Disease (AD) diagnosed by the neurology service; more than 65 years. Exclusion criteria: Comorbidity with other significant neurology disease, infectious treatment with antibiotics in the previous 6 months prior to providing the stool sample, corticosteroid use, immunosuppressors or immunostimulants treatment, illnesses of the gastrointestinal (GI) tract, large doses of commercial probiotics consumed (greater than or equal to 108 colony forming units (cfu) per organisms per day). Neuropsychological, functional and neuropsychiatric assessment and stool sample at basal, 12 weeks and 24 weeks. |
| Alzheimer disease (AD)-probiotic | – | Dietary Supplement: Probiotic supplementInclusion criteria: Alzheimer Disease (AD) diagnosed by the neurology service; more than 65 years. Exclusion criteria: Comorbidity with other significant neurology disease, infectious treatment with antibiotics in the previous 6 months prior to providing the stool sample, corticosteroid use, immunosuppressors or immunostimulants treatment, illnesses of the gastrointestinal (GI) tract, large doses of commercial probiotics consumed (greater than or equal to 108 colony forming units (cfu) per organisms per day). Neuropsychological, functional and neuropsychiatric assessment and stool sample at basal, 12 weeks and 24 weeks. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Clinic patients from hospitals and other diagnostic medical centers.
Key inclusion criteria (6 listed)
- Study 1, microbiota composition study- AD, PD, LBD, FTD-behavioral variant or MCI-amnesic
- diagnosed by the neurology service (or healthy subjects, without any of these diagnostics).
- more than 60 years
- AD diagnosed by the neurology service;
- more than 65 years.
Key exclusion criteria (14 listed)
- Comorbidity with other significant neurology disease,
- Infectious treatment with antibiotics in the previous 6 months prior to providing the stool sample,
- corticosteroid use,
- immunosuppressors or immunostimulants treatment,
- illnesses of the Gastro Intestinal tract,
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 |
|---|---|---|
| No interventionno intervention | Other | Alzheimer Disease (AD), Frontotemporal Dementia (FTD)-behavioral variant, Healthy control group, Lewy bodies dementia (LBD), Mild Cognitive Impairment (MCI)- amnesic, Parkinson Disease Dementia (PDD) |
| Probiotic supplementA total of 60 Alzheimer Disease (AD) patients will be recruited, 30 will ingest the probiotic mixture and 30 will ingest placebo (randomized assignment to the groups will be done). The experimental group will take the probiotic ingest daily: Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, and Lactobacillus fermentum (2 × 109 colony forming units (CFU)/g of each). This mixture of bacteria has been showed to have positive results with 12 weeks treatment. | Dietary supplement | Alzheimer disease (AD)-control, Alzheimer disease (AD)-probiotic |
Primary outcome
Shotgun sequencing metagenomics analysis (NextSeq2000)
Time frame: Baseline for all the group subjects subjects in microbiota composition study. Baseline, change from baseline at 12 weeks and change from baseline at 24 weeks for Alzheimer Disease (AD) patients in the probiotic study.
Gut microbiome was analysed using a shotgun metagenomic approach. DNA was extracted from samples using the DNA Preparation with Tagmentation kit, according to manufacturer protocols (Illumina, California, USA, catalog no. 20018705). Sequencing libraries concentration was determined by Qubit 4.0 fluorometer and Qubit dsDNA High Sensivity Assay Kit (Thermo Fisher Scientific, Massachusetts, USA). Sequencing libraries length was checked by Agilent TapeStation and Agilent High Sensitivity DNA kit (Agilent Technologies, California, USA). Sequencing libraries with concentration below 750 per Molar and length out of 400-600 bp range were discarded. Final sequencing libraries were mixed at 750 bp and sequenced using the NextSeq 2000 sequencing system (Illumina, California, USA) as 2x150-bp paired-end reads. Samples below 7,5 million reads were discarded. Shotgun metagenomic reads were profiled for microbial species relative abundances by mapping them to several databases with Kraken2.
Neuropsychology assessment: Mini Mental State Examination (MMSE)
Time frame: Baseline for all the group subjects subjects in microbiota composition study. Baseline, change from baseline at 12 weeks and change from baseline at 24 weeks for AD patients in the probiotic study.
Mini Mental State Examination (MMSE), screening test for cognitive deterioration. At Baseline for no intervention study, study 1. For the probiotic study, study 2, at baseline, change at 12 weeks and change at 24 weeks
Neuropsychology assessment: Global Deterioration Scale-Functional Assessment Staging (GDS-FAST)
Time frame: Baseline for all the group subjects subjects in microbiota composition study. Baseline, change from baseline at 12 weeks and change from baseline at 24 weeks for AD patients in the probiotic study.
Global Deterioration Scale-Functional Assessment Staging (GDS-FAST) At Baseline for no intervention study, study 1. For the probiotic study, study 2, at baseline, change from baseline at 12 weeks and change from baseline at 24 weeks.
Neuropsychology assessment: Clinical Dementia Rating (CDR)
Time frame: Baseline for all the group subjects subjects in microbiota composition study. Baseline, change from baseline at 12 weeks and change from baseline at 24 weeks for AD patients in the probiotic study.
Clinical Dementia Rating (CDR) score. At Baseline for no intervention study, study 1. For the probiotic study, study 2, at baseline, change from the baseline at 12 weeks and change from baseline at 24 weeks.
Neuropsychology assessment: Memory Impairment Screen (MIS)
Time frame: Baseline for all the group subjects subjects in microbiota composition study.
Memory Impairment Screen (MIS). Screening test for memory impairment. At Baseline for no intervention study, study 1.
Neuropsychology assessment: Categorical Recall Test (Barcelona-2 Test)
Time frame: Baseline for all the group subjects subjects in microbiota composition study.
Categorical Recall Test (Barcelona-2 Test), semantic and phonemic fluency tests At Baseline for no intervention study, study 1.
Neuropsychology assessment: Orientation
Time frame: Baseline for all the group subjects subjects in microbiota composition study.
Orientation in Time, Space and Person (Barcelona-2 Test) At Baseline for no intervention study, study 1.
Neuropsychology assessment: Free and Cue Selective Reminding Test (FCSRT)
Time frame: Baseline for all the group subjects subjects in microbiota composition study.
Free and Cue Selective Reminding Test (FCSRT). Long and short Memory assessment test. At Baseline for no intervention study, study 1.
Neuropsychology assessment: Trial Making Test (TMT) A and B
Time frame: Baseline for all the group subjects subjects in microbiota composition study.
TMT A and B. Measures visuospatial, attention and executive functions. At Baseline for no intervention study, study 1.
Neuropsychology assessment: Boston Abbreviated Naming Test
Time frame: Baseline for all the group subjects subjects in microbiota composition study.
Boston Abbreviated Naming Test At Baseline for no intervention study, study 1.
Neuropsychology assessment: Verbal span
Time frame: Baseline for all the group subjects subjects in microbiota composition study.
Verbal Span (Barcelona-2 Test), that assesses attentional span and control/working memory. At Baseline for no intervention study, study 1.
Neuropsychology assessment: Clock test
Time frame: Baseline for all the group subjects subjects in microbiota composition study.
Clock Test, screening test for detecting cognitive impairment At Baseline for no intervention study, study 1.
Neuropsychology assessment: Frontal Assessment Battery (FAB)
Time frame: Baseline for all the group subjects subjects in microbiota composition study.
Frontal Assessment Battery (FAB), that assesses impairments related to frontal lobe function. At Baseline for no intervention study, study 1.
Neuropsychology assessment: Simple and semi complex constructive praxis (Barcelona-2 Test)
Time frame: Baseline for all the group subjects subjects in microbiota composition study.
Simple and semi complex constructive praxis (Barcelona-2 Test) At Baseline for no intervention study, study 1.
Neuropsychology assessment: Abbreviated Barcelona-2 Test
Time frame: Baseline, change from baseline at 12 weeks and change from baseline at 24 weeks for AD patients in the probiotic study.
Abbreviated Barcelona-2 Test. Abbreviated neuropsychological battery already normalised in Spanish populations. Only for the probiotic study, study 2, at baseline, change from baseline at 12 weeks and change from baseline at 24 weeks.
Neuropsychiatric assessment: Golberg Anxiety and Depression Scale
Time frame: Baseline for all the group subjects subjects in microbiota composition study. Baseline, change from baseline at 12 weeks and change from baseline at 24 weeks for AD patients in the probiotic study.
Golberg Anxiety and Depression Scale (more punctuation, more anxiety or depression symptoms) At Baseline for no intervention study For the probiotic study: At baseline, change from baseline at 12 weeks and change from baseline at 24 weeks.
Neuropsychiatric assessment: Neuropsychiatric Symptoms (Barcelona-2 Test)
Time frame: Baseline for all the group subjects subjects in microbiota composition study. Baseline, change from baseline at 12 weeks and change from baseline at 24 weeks for AD patients in the probiotic study.
For microbiota composition study, the following tests will be assessed: Neuropsychiatric Symptoms (Barcelona-2 Test), (more punctuation, more neuropsychiatric symptoms) At Baseline for no intervention study For the probiotic study: At baseline, change from baseline at 12 weeks and change from baseline 24 weeks.
Functional assessment
Time frame: Baseline for all the group subjects subjects in microbiota composition study. Baseline, change from baseline at 12 weeks and change from baseline at 24 weeks for AD patients in the probiotic study.
For microbiota composition study, the following tests will be assessed: Activities of Daily Living (ADL) (Barcelona-2 Test), (more punctuation, more dependent; punctuation total scale 0-100, Instrumental activities 0-60 + Basic activities 0-40) At Baseline for no intervention study For the probiotic study: At baseline, change from baseline at 12 weeks and change from baseline at 24 weeks, the following tests will be assessed: Activities of Daily Living ADL (Barcelona-2 Test), (more punctuation, more dependent; punctuation total scale 0-100, Instrumental activities 0-60 + Basic activities 0-40)
3 secondary outcomes
Assessment of stress events
Time frame: Baseline for all the group subjects subjects in microbiota composition study. Baseline, change from baseline at 12 weeks and change from baseline at 24 weeks for AD patients in the probiotic study.
Mediterranean lifestyle assessment
Time frame: Baseline for all the group subjects subjects in microbiota composition study. Baseline, change from baseline at 12 weeks and change from baseline at 24 weeks for AD patients in the probiotic study.
Cognitive reserve assessment
Time frame: Baseline for all the group subjects subjects in microbiota composition study. Baseline, change from baseline at 12 weeks and change from baseline at 24 weeks for AD patients in the probiotic study.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2023.
- Background: PubMed 34911422Cabrera C, Vicens P, Torrente M. Modifiable Risk Factors for Dementia: The Role of Gut Microbiota. Curr Alzheimer Res. 2021;18(13):993-1009. doi: 10.2174/1567205018666211215152411.
- Background: PubMed 30158897Agahi A, Hamidi GA, Daneshvar R, Hamdieh M, Soheili M, Alinaghipour A, Esmaeili Taba SM, Salami M. Does Severity of Alzheimer's Disease Contribute to Its Responsiveness to Modifying Gut Microbiota? A Double Blind Clinical Trial. Front Neurol. 2018 Aug 15;9:662. doi: 10.3389/fneur.2018.00662. eCollection 2018.
- Background: PubMed 27891089Akbari E, Asemi Z, Daneshvar Kakhaki R, Bahmani F, Kouchaki E, Tamtaji OR, Hamidi GA, Salami M. Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial. Front Aging Neurosci. 2016 Nov 10;8:256. doi: 10.3389/fnagi.2016.00256. eCollection 2016.
- Background: PubMed 17151594Benton D, Williams C, Brown A. Impact of consuming a milk drink containing a probiotic on mood and cognition. Eur J Clin Nutr. 2007 Mar;61(3):355-61. doi: 10.1038/sj.ejcn.1602546. Epub 2006 Dec 6.
- Background: PubMed 23500100Davari S, Talaei SA, Alaei H, Salami M. Probiotics treatment improves diabetes-induced impairment of synaptic activity and cognitive function: behavioral and electrophysiological proofs for microbiome-gut-brain axis. Neuroscience. 2013 Jun 14;240:287-96. doi: 10.1016/j.neuroscience.2013.02.055. Epub 2013 Mar 7.
- Background: PubMed 27865949Kelly JR, Allen AP, Temko A, Hutch W, Kennedy PJ, Farid N, Murphy E, Boylan G, Bienenstock J, Cryan JF, Clarke G, Dinan TG. Lost in translation? The potential psychobiotic Lactobacillus rhamnosus (JB-1) fails to modulate stress or cognitive performance in healthy male subjects. Brain Behav Immun. 2017 Mar;61:50-59. doi: 10.1016/j.bbi.2016.11.018. Epub 2016 Nov 16.
- Background: PubMed 20974015Messaoudi M, Lalonde R, Violle N, Javelot H, Desor D, Nejdi A, Bisson JF, Rougeot C, Pichelin M, Cazaubiel M, Cazaubiel JM. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br J Nutr. 2011 Mar;105(5):755-64. doi: 10.1017/S0007114510004319. Epub 2010 Oct 26.
- Background: PubMed 30700769Saji N, Niida S, Murotani K, Hisada T, Tsuduki T, Sugimoto T, Kimura A, Toba K, Sakurai T. Analysis of the relationship between the gut microbiome and dementia: a cross-sectional study conducted in Japan. Sci Rep. 2019 Jan 30;9(1):1008. doi: 10.1038/s41598-018-38218-7.
- Background: PubMed 23474283Tillisch K, Labus J, Kilpatrick L, Jiang Z, Stains J, Ebrat B, Guyonnet D, Legrain-Raspaud S, Trotin B, Naliboff B, Mayer EA. Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology. 2013 Jun;144(7):1394-401, 1401.e1-4. doi: 10.1053/j.gastro.2013.02.043. Epub 2013 Mar 6.
- Background: PubMed 29051531Vogt NM, Kerby RL, Dill-McFarland KA, Harding SJ, Merluzzi AP, Johnson SC, Carlsson CM, Asthana S, Zetterberg H, Blennow K, Bendlin BB, Rey FE. Gut microbiome alterations in Alzheimer's disease. Sci Rep. 2017 Oct 19;7(1):13537. doi: 10.1038/s41598-017-13601-y.
- Background: PubMed 34474192Soldevila-Domenech N, Forcano L, Vintro-Alcaraz C, Cuenca-Royo A, Pinto X, Jimenez-Murcia S, Garcia-Gavilan JF, Nishi SK, Babio N, Gomis-Gonzalez M, Corella D, Sorli JV, Fernandez-Carrion R, Martinez-Gonzalez MA, Marti A, Salas-Salvado J, Castaner O, Fernandez-Aranda F, Torre R. Interplay between cognition and weight reduction in individuals following a Mediterranean Diet: Three-year follow-up of the PREDIMED-Plus trial. Clin Nutr. 2021 Sep;40(9):5221-5237. doi: 10.1016/j.clnu.2021.07.020. Epub 2021 Aug 5.
- Background: PubMed 6501581Buschke H. Cued recall in amnesia. J Clin Neuropsychol. 1984 Nov;6(4):433-40. doi: 10.1080/01688638408401233.
- Pena-Casanova J. (2019). Teoria e Interpretacion: Normalidad, Semiologia y Patologia Neuropsicologicas. Programa integrado de exploracion neuropsicologica. Test Barcelona-2. Masquelibros, S.L., Jaen. International Standrad Book Number: 978-84-120274-0-2.Link provided by the sponsor.
- Individual participant dataSharing planned: Undecided. It is not decided yet.
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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.
Margarita Torrente, Dr principal investigator
University Rovira i Virgili
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 Dementia Alzheimers and Dementia With Lewy Bodies, run by University Rovira i Virgili at 1 site in Spain.
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 6 inclusion and 14 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: status not confirmed, as of the sponsor's last update on 13 Jul 2023. 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 Spain. 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 Margarita Torrente, Dr (+34977558176, margarita.torrente@urv.cat), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Shotgun sequencing metagenomics analysis (NextSeq2000) (time frame: Baseline for all the group subjects subjects in microbiota composition study. Baseline, change from baseline at 12 weeks and change from baseline at 24 weeks for Alzheimer Disease (AD) patients in the probiotic study.). The study lists 18 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05943925, which also lists 23 linked publications.
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 13 Jul 2023.