- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03847714
Probiotics in Dementia (PIDE)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Dementia is a disease that presents with deterioration in memory, thinking, behaviour and the ability to perform everyday activities. Worldwide 47.5 million people are affected and incidence of dementia is increasing. Dementia leads to disability and dependency among older people worldwide and thereby has a huge physical, psychological, social and economic impact on caregivers, families and society. Alzheimer's disease (AD) is the most common form of dementia accounting for 60-70% of the cases; other forms include Lewy body dementia, frontotemporal dementia, vascular dementia and Parkinson's disease with dementia. In AD, pathologic protein aggregates of amyloid beta and hyperphosphorylated tangles of tau-protein which deposit as neurofibrillary tangles are typical features. This leads to neuroinflammation, mainly mediated by the innate immune system. The most important cells in this process are microglia cells, which represent the resident macrophages of the brain. Although microglia is able to remove extracellular amyloid beta, in later stages of the disease cells remain in a dystrophic state and cannot exert their beneficial functions. Microglia maturation and function is critically dependent on short-chain fatty acids produced by the gut microbiome and therefore highlights the microbiome as a potential diagnostic and therapeutic target in dementia.
The role of the commensal microbial population of the human body - especially the intestinal microbiome - in various diseases is emerging due to the development of advanced analysis techniques. Recently the concept of the gut brain-axis has been established. Several pathways including the autonomic nervous system, the enteric nervous system, the neuroendocrine system and the immune system allow a communication between gut and brain but may also be involved in disease development.
During ageing, the gut microbiome composition undergoes changes. A decrease in diversity, a loss of beneficial taxa and an increase of facultative pathogens has been described. Diet and the place of residence play an important role in the shaping of the microbiome. Aging is also associated with inflammation - often termed as "inflammaging" associated with an increase in gut permeability, mucosal inflammation and bacterial translocation.
Since the main risk factor for developing dementia, especially AD, is aging, it is very likely that the gut-brain axis is critically involved in dementia development.
Animal studies so far suggest that AD is associated with changes in the gut microbiome composition with a decrease in beneficial, anti-inflammatory genera. Furthermore, genetic alterations in amyloid genes can influence microbiome composition in mice, pointing towards a vicious cycle in AD development.
In humans, so far only limited evidence on the microbiome composition in patients with dementia is available. There is evidence that the composition of the microbiome in subgingival plaques is altered in dementia and associated with cognitive function. Recently the first human study identified phylum- through genus-wide differences in bacterial abundance including decreased Firmicutes, increased Bacteroidetes, and decreased Bifidobacterium in the stool of AD patients.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
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Graz, Austria
- Medical University Graz
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Age >18 years
- Dementia of Alzheimer type and mixed type (diagnosis by a board-certified neurologist/psychiatrist and according to ICD10)
- Mini Mental State Examination 21-26
- Stable treatment with anti-dementia drugs including phytotherapeutics (>3 months) or no intention to start anti-dementia drugs
- Informed consent
Exclusion Criteria:
- Other forms of dementia
- Inflammatory bowel diseases
- Liver cirrhosis
- Antibiotic treatment within the last 4 weeks
- Febrile illness within the last 4 weeks
- Acute hospital admission for dementia-unrelated reasons within the last 4 weeks
- Dysphagia
- Any other condition or circumstance, which, in the opinion of the investigator, would affect the patient's ability to participate in the protocol
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Probiotic
Bifidobacterium bifidum W23, B. lactis W51, B. lactis W52, Lactobacillus acidophilus W22, L. casei W56, L. paracasei W20, L. plantarum W62, L. salivarius W24, Lactococcus lactis W19, 7.5 × 109 Colony Forming Units/g twice daily dissolved in water
|
The probiotic supplement is a commercially available food for special medical purposes and includes 9 bacterial strains with at least 7.5 billion organisms (7.5 × 109 Colony Forming Units/g) per 1 portion (= 3 g).
Other Names:
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Placebo Comparator: Placebo
3g of a similar looking and tasting powder, twice daily
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similar looking and tasting powder
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Butyrate producing bacteria
Time Frame: 6 months
|
abundance of butyrate producing bacteria
|
6 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Butyrate producing bacteria
Time Frame: 12 months
|
abundance of butyrate producing bacteria
|
12 months
|
diaminooxidase concentration in serum
Time Frame: 6 months
|
marker of intestinal permeability
|
6 months
|
diaminooxidase concentration in serum
Time Frame: 12 months
|
marker of intestinal permeability
|
12 months
|
zonulin concentration in stool
Time Frame: 6 months
|
marker of intestinal permeability
|
6 months
|
zonulin concentration in stool
Time Frame: 12 months
|
marker of intestinal permeability
|
12 months
|
calprotectin concentration in stool
Time Frame: 6 months
|
marker of intestinal inflammation
|
6 months
|
calprotectin concentration in stool
Time Frame: 12 months
|
marker of intestinal inflammation
|
12 months
|
soluble CD 14 concentration in serum
Time Frame: 6 months
|
marker of systemic inflammation
|
6 months
|
soluble CD 14 concentration in serum
Time Frame: 12 months
|
marker of systemic inflammation
|
12 months
|
lipopolysaccharide binding protein concentration in serum
Time Frame: 6 months
|
marker of systemic inflammation
|
6 months
|
lipopolysaccharide binding protein concentration in serum
Time Frame: 12 months
|
marker of systemic inflammation
|
12 months
|
lipopolysaccharide concentration in serum
Time Frame: 6 months
|
marker of bacterial translocation
|
6 months
|
lipopolysaccharide concentration in serum
Time Frame: 12 months
|
marker of bacterial translocation
|
12 months
|
peptidoglycan concentration in serum
Time Frame: 6 months
|
marker of bacterial translocation
|
6 months
|
peptidoglycan concentration in serum
Time Frame: 12 months
|
marker of bacterial translocation
|
12 months
|
bacterial DNA concentration in serum
Time Frame: 6 months
|
marker of bacterial translocation
|
6 months
|
bacterial DNA concentration in serum
Time Frame: 12 months
|
marker of bacterial translocation
|
12 months
|
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS cog)
Time Frame: 6 months
|
Questionnaire to assess cognitive function, 0-70 points
|
6 months
|
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS cog)
Time Frame: 12 months
|
Questionnaire to assess cognitive function, 0-70 points
|
12 months
|
Mini mental state examination
Time Frame: 6 months
|
Questionnaire to assess cognitive function, 0-30 points
|
6 months
|
Mini mental state examination
Time Frame: 12 months
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Questionnaire to assess cognitive function, 0-30 points
|
12 months
|
clinician's interview-based impression of change with caregiver input (CIBIC+)
Time Frame: 6 months
|
Questionnaire to assess overall change during the study, 1-7 points
|
6 months
|
clinician's interview-based impression of change with caregiver input (CIBIC+)
Time Frame: 12 months
|
Questionnaire to assess overall change during the study, 1-7 points
|
12 months
|
Barthel index
Time Frame: 6 months
|
Assessment of activities of daily living, 0-100 points
|
6 months
|
Barthel index
Time Frame: 12 months
|
Assessment of activities of daily living, 0-100 points
|
12 months
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- PIDE
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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