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NCT Number: NCT06837272

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

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.

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Key information

Age range

60 year–80 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Cognitively normal group:
  • normal performance on standardized cognitive tests;
  • with no cognitive complaints or any concerns (worries).
  • SCD group:
  • self-experienced persistent decline in memory, rather than other domains of cognition;
  • normal performance on standardized cognitive tests;
  • failure to meet the criteria for MCI or dementia;
  • age at onset of SCD ≥ 60 years old;
  • onset of SCD within the last 5 years;
  • concerns (worries) associated with SCD;
  • feeling of worse performance than others of the same age group.
  • MCI group:
  • having impaired scores on both measures in at least one cognitive domain (memory, language, or speed/executive function);
  • having impaired scores in each of the three cognitive domains (memory, language, or speed/executive function);
  • the Functional Activities Questionnaire (FAQ)≥9.
  • AD dementia group:
  • meet the criteria for dementia and have impaired daily functional activities;
  • 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

Treatment and study plan

Multi-omics features extraction

Diagnostic Test

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.

Primary outcomes

  1. 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.

  2. 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.

  3. 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.

Secondary outcomes

  1. 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".

Study contacts

Contact information is provided by the study sponsor or research team.

Can Sheng, PhD

CONTACT

[email protected]

86-18701257298

Yun Guo, Master

CONTACT

[email protected]

86-18863030588

Sponsors and collaborators

Lead sponsor

Jining Medical University

Other

Collaborators

  • Xuanwu Hospital, Beijing

Registry information

Official study title

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)

Important dates

Study start
2024
Primary completion
2026
Study completion
2029
First posted
Feb 20, 2025
Registry last updated
Feb 20, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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