A Longitudinal Study to Explore the Impact of Gut Microbiome on Brain Health in Alzheimer's Disease

February 15, 2025 updated by: Can Sheng, Jining Medical University

A Longitudinal Study to Explore the Impact of Gut Microbiome on Brain Health in Alzheimer's Disease: China Healthy Brain and Gut Microbiome Study (CHBGMS)

Gut microbiota dysfunction is associated with Alzheimer's disease (AD). However, the potential modulatory mechanism remains unclear. Previous studies have shown that gut-derived metabolites short-chain fatty acids (SCFAs) may be the key mediators between gut microbiota and brain, participating in the modulatory pathway "gut microbiota-SCFAs-brain networks". In this project, high-throughput targeted metabolomics technique will be used to explore the differences of SCFAs in the spectrum of AD, including cognitively normal individuals, subjective cognitive decline (SCD), mild cognitive impairment (MCI), and AD dementia. Then, the gut microbiome and multi-modal MRI techniques will be combined to elucidate potential interaction mechanisms of "gut microbiota-SCFAs-brain networks". Finally, based on multi-omics features extracted from gut microbiome, metabolomics, and neuroimaging after five years, the diagnostic model of SCD due to preclinical AD will be established using machine learning methods.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Estimated)

285

Contacts and Locations

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

Study Contact

Study Contact Backup

Study Locations

  • China
    • Shandong
      • Jining, Shandong, China, 272029
        • Recruiting
        • Department of Neurolgy, the Affiliated Hospital of Jining Medical University
        • Contact:
        • Contact:

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Probability Sample

Study Population

Volunteers recruited from both clinical and communities, and signed up with informed consent.

Description

Inclusion Criteria:

  • Cognitively normal group:

    1. normal performance on standardized cognitive tests;
    2. with no cognitive complaints or any concerns (worries).

  • SCD group:

    1. self-experienced persistent decline in memory, rather than other domains of cognition;
    2. normal performance on standardized cognitive tests;
    3. failure to meet the criteria for MCI or dementia;
    4. age at onset of SCD ≥ 60 years old;
    5. onset of SCD within the last 5 years;
    6. concerns (worries) associated with SCD;
    7. feeling of worse performance than others of the same age group.

  • MCI group:

    1. having impaired scores on both measures in at least one cognitive domain (memory, language, or speed/executive function);
    2. having impaired scores in each of the three cognitive domains (memory, language, or speed/executive function);
    3. the Functional Activities Questionnaire (FAQ)≥9.

  • AD dementia group:

    1. meet the criteria for dementia and have impaired daily functional activities;
    2. episodic memory deficit; 3) Clinical Dementia Rating (CDR) ≥ 1.

Exclusion Criteria:

  • a history of stroke;
  • major depression and anxiety;
  • other central nervous system disorders that may cause cognitive impairment, such as Parkinson's disease, tumors, encephalitis, and epilepsy;
  • cognitive impairment caused by traumatic brain injury;
  • systemic diseases, such as thyroid dysfunction, syphilis and HIV;
  • psychosis or congenital mental developmental delay;
  • a history of using antibiotics, probiotics, prebiotics, or synbiotics within 3 months;
  • the use of corticosteroid, immune stimulating medications, and immunosuppressive agents;
  • major gastrointestinal tract surgery in past 5 years;
  • severe gastrointestinal diseases, such as irritable bowel syndrome, infammatory bowel disease, severe gastritis, other dysfunction in digestion and absorption, which has been reported to infuence gut microbiota

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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Cognitively normal group
(1) normal performance on standardized cognitive tests; (2) with no cognitive complaints or any concerns (worries).
Subjective cognitive decline (SCD) group
(1) self-experienced persistent decline in memory, rather than other domains of cognition; (2) normal performance on standardized cognitive tests; (3) failure to meet the criteria for MCI or dementia; (4) age at onset of SCD ≥ 60 years old; (5) onset of SCD within the last 5 years; (6) concerns (worries) associated with SCD; (7) feeling of worse performance than others of the same age group.
Diagnostic test: Multi-omics features extraction
Based on multi-omics features extracted from clinical data, gut microbiome, metabolomics, and multi-modal MRI, the diagnostic model of SCD due to preclinical AD will be established.
Mild cognitive impairment (MCI) group
(1) having impaired scores on both measures in at least one cognitive domain (memory, language, or speed/executive function); (2) having impaired scores in each of the three cognitive domains (memory, language, or speed/executive function); (3) the Functional Activities Questionnaire (FAQ)≥9.
AD dementia group
(1) meet the criteria for dementia and have impaired daily functional activities; (2) episodic memory deficit; 3) Clinical Dementia Rating (CDR) ≥ 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The changes of gut microbiome in the spectrum of AD
Time Frame: 5 year
Using the 16S rRNA Illumina Miseq sequencing technique, the diversity and compositions of gut microbiome will be compared in different stages of AD, including cognitively normal individuals, SCD, MCI and AD dementia.
5 year
The changes of SCFAs in the spectrum of AD
Time Frame: 5 year
Using the high-throughput target metabolomics technique, SCFAs will be compared in different stages of AD, including cognitively normal individuals, SCD, MCI and AD dementia.
5 year
Multi-omics biomarkers associated with conversion to cognitive impairment for SCD subjects
Time Frame: 5 years
SCD subjects will be followed for five years. The investigators aim to characterize those who convert to MCI or AD dementia during the follow-up, and further find the multi-omics features associated with the progression of AD. Based on multi-omics features extracted from clinical data, gut microbiome, metabolomics, and multi-modal MRI, the diagnostic model of SCD due to preclinical AD will be established.
5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The interaction mechanisms of "gut microbiota-SCFAs-brain networks"
Time Frame: 5 years
The gut microbiome, SCFAs and multi-modal MRI techniques will be combined to elucidate potential interaction mechanisms of "gut microbiota-SCFAs-brain networks".
5 years

Collaborators and Investigators

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

Sponsor

Jining Medical University

Collaborators

Xuanwu Hospital, Beijing

Investigators

  • Principal Investigator: Can Sheng, PhD, The Affiliated Hospital of Jining Medical University

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)

January 1, 2024

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2029

Study Registration Dates

First Submitted

February 15, 2025

First Submitted That Met QC Criteria

February 15, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 15, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • JiningMU_Shc1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The information of neuropsychological tests, and other clinical data are to be shared with other researchers.

IPD Sharing Time Frame

When summary data are published or starting 12 months after publication.

IPD Sharing Access Criteria

When summary data are published or starting 12 months after publication.

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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