Precision Probiotic Supplementation in Individuals With Mild Cognitive Impairment

Summary

The overarching goal of this randomized-controlled trial is to investigate the role and mechanism of the microbiota-gut-brain axis in MCI. The main questions it aims to answer are:

Aim 1: To investigate the association between gut microbiota, MCI and AD biomarkers. Investigators plan to compare gut microbiota profiles in a well-characterized cohort between individuals with MCI and cognitively normal adults using metagenomics sequencing data. Also, the relationship between gut microbiota and AD biomarkers, such as amyloid PET and plasma tau, will be explored in MCI and cognitively normal adults.

Aim 2: To determine the efficacy of precision probiotic supplementation on cognitive decline (primary outcome) and functional brain changes (secondary outcome) in individuals with MCI due to AD using a randomized, double-blind, placebo-controlled trial. Investigators plan to recruit 120 individuals with MCI due to AD, i.e., MCI with positive amyloid biomarkers. Participants will be randomized to a 12-month supplement of precision probiotics based on the individual gut probiotic profile or placebo. The primary outcome measure will be the changes in cognitive functions over 6 months (primary endpoint) and 12 months. The secondary outcome measure will be resting-state functional brain changes.

Aim 3: To investigate potential mediators underlying the effect of probiotic supplementation. The most apparent mediator will be a shift or changes in gut microbiota. Other potential mediators will be related to decreased lipopolysaccharide, proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6 and IL-10, and increased brain- derived neurotrophic factor, short-chain fatty acid, etc.

Conditions

• Mild Cognitive Impairment

Interventions

DIETARY_SUPPLEMENT

Precision probiotics

The precision probiotics will be designed based on the results of probiotic signatures and consensus clustering described in the PRELIMINARY AND SUPPORTING Data section and available probiotics from GenMont Biotech Inc. (https://www.genmont.com.tw/) The individual gut microbiota will determine the supplement and composition of probiotics.

Sponsors & Collaborators

• National Science and Technology Council

  collaborator FED

• Far Eastern Memorial Hospital

  collaborator OTHER

• National Yang Ming Chiao Tung University

  lead OTHER

Principal Investigators

• Yen-Ling Chiu · Far Eastern Memorial Hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

60 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-03-18

Primary Completion

2025-07-31

Completion

2027-07-31