Probiotics in Dementia

Dementia; Alzheimer, Mixed Type (Etiology) Clinical Trial

— PIDE  

Official title:

Probiotics in Dementia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03847714
• Other study ID #: PIDE
• Status: Active, not recruiting
• Phase: N/A
• Start date: June 15, 2019
• Est. completion date: December 2025

Study information

• Verified date: March 2024
• Source: Medical University of Graz
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Dementia is associated with changes in gut microbiome composition, gut barrier dysfunction, intestinal inflammation and systemic inflammation. Probiotics are a possibility to modulate the gut-brain axis. In this study the effect of probiotics on the gut microbiome and, gut barrier function, inflammation and cognitive dysfunction will be studied.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 58
• Est. completion date: December 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Dementia
• Dementia; Alzheimer, Mixed Type (Etiology)

Intervention

Dietary Supplement:
• Omni-Biotic Stress Repair
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).
• placebo
similar looking and tasting powder

Locations

Country	Name	City	State
Austria	Medical University Graz	Graz

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Graz

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Butyrate producing bacteria	abundance of butyrate producing bacteria	6 months
Secondary	Butyrate producing bacteria	abundance of butyrate producing bacteria	12 months
Secondary	diaminooxidase concentration in serum	marker of intestinal permeability	6 months
Secondary	diaminooxidase concentration in serum	marker of intestinal permeability	12 months
Secondary	zonulin concentration in stool	marker of intestinal permeability	6 months
Secondary	zonulin concentration in stool	marker of intestinal permeability	12 months
Secondary	calprotectin concentration in stool	marker of intestinal inflammation	6 months
Secondary	calprotectin concentration in stool	marker of intestinal inflammation	12 months
Secondary	soluble CD 14 concentration in serum	marker of systemic inflammation	6 months
Secondary	soluble CD 14 concentration in serum	marker of systemic inflammation	12 months
Secondary	lipopolysaccharide binding protein concentration in serum	marker of systemic inflammation	6 months
Secondary	lipopolysaccharide binding protein concentration in serum	marker of systemic inflammation	12 months
Secondary	lipopolysaccharide concentration in serum	marker of bacterial translocation	6 months
Secondary	lipopolysaccharide concentration in serum	marker of bacterial translocation	12 months
Secondary	peptidoglycan concentration in serum	marker of bacterial translocation	6 months
Secondary	peptidoglycan concentration in serum	marker of bacterial translocation	12 months
Secondary	bacterial DNA concentration in serum	marker of bacterial translocation	6 months
Secondary	bacterial DNA concentration in serum	marker of bacterial translocation	12 months
Secondary	Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS cog)	Questionnaire to assess cognitive function, 0-70 points	6 months
Secondary	Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS cog)	Questionnaire to assess cognitive function, 0-70 points	12 months
Secondary	Mini mental state examination	Questionnaire to assess cognitive function, 0-30 points	6 months
Secondary	Mini mental state examination	Questionnaire to assess cognitive function, 0-30 points	12 months
Secondary	clinician's interview-based impression of change with caregiver input (CIBIC+)	Questionnaire to assess overall change during the study, 1-7 points	6 months
Secondary	clinician's interview-based impression of change with caregiver input (CIBIC+)	Questionnaire to assess overall change during the study, 1-7 points	12 months
Secondary	Barthel index	Assessment of activities of daily living, 0-100 points	6 months
Secondary	Barthel index	Assessment of activities of daily living, 0-100 points	12 months