protocolSection identificationModule nctId: NCT06278688, orgStudyIdInfo id: 112R10438Y, briefTitle: Precision Probiotic Supplementation in Individuals With Mild Cognitive Impairment, statusModule overallStatus: NOT_YET_RECRUITING, startDateStruct date: 2024-03-18, primaryCompletionDateStruct date: 2025-07-31, completionDateStruct date: 2027-07-31, studyFirstPostDateStruct date: 2024-02-26, lastUpdatePostDateStruct date: 2024-02-26, sponsorCollaboratorsModule leadSponsor name: National Yang Ming University, class: OTHER, collaborators name: National Science and Technology Council, collaborators name: Far Eastern Memorial Hospital, descriptionModule briefSummary: 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., conditionsModule conditions: Mild Cognitive Impairment, designModule studyType: INTERVENTIONAL, phases: NA, designInfo allocation: RANDOMIZED, interventionModel: PARALLEL, primaryPurpose: TREATMENT, maskingInfo masking: DOUBLE, whoMasked: PARTICIPANT, whoMasked: INVESTIGATOR, enrollmentInfo count: 120, type: ESTIMATED, armsInterventionsModule interventions name: Precision probiotics, outcomesModule primaryOutcomes measure: The changes in attention, primaryOutcomes measure: The changes in memory, primaryOutcomes measure: The changes in executive function, secondaryOutcomes measure: The changes in global cognition at the 12th month from baseline., secondaryOutcomes measure: The changes in brain imaging at the 12th month from baseline., eligibilityModule sex: ALL, minimumAge: 60 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule, hasResults: False