Probiotics in Dementia (PIDE)

March 12, 2024 updated by: Medical University of Graz
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.

Study Overview

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

Interventional

Enrollment (Estimated)

58

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Graz, Austria
        • Medical University Graz

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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:
  • Omni-Biotic SR-9, Winclove 825
Placebo Comparator: Placebo
3g of a similar looking and tasting powder, twice daily
similar looking and tasting powder

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
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

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 15, 2019

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

February 11, 2019

First Submitted That Met QC Criteria

February 18, 2019

First Posted (Actual)

February 20, 2019

Study Record Updates

Last Update Posted (Actual)

March 13, 2024

Last Update Submitted That Met QC Criteria

March 12, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

microbiome sequencing data will be published at nucleotide archive

IPD Sharing Time Frame

at time of publication; no limit

IPD Sharing Access Criteria

open

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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