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Microbiome Composition and Function Contributes to Cognitive Impairment and Neuroinflammation in Parkinson's Disease

Sponsor
California State University, San Bernardino (Other)
Overall Status
Recruiting
CT.gov ID
NCT05419453
Collaborator
National Institutes of Health (NIH) (NIH), National Institute of Neurological Disorders and Stroke (NINDS) (NIH)
100
Enrollment
1
Location
59
Anticipated Duration (Months)
1.7
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Cognitive impairment is a common non-motor symptom among individuals living with Parkinson's disease (PD). Traditionally, cognitive impairment is thought to reflect disruptions in dopaminergic frontal-striatal systems. However, the current conceptualization does not thoroughly explain the heterogeneous profiles or trajectories of cognitive impairment in PD; suggesting that alternative mechanisms may contribute to cognitive impairments. Identification of alternative mechanisms of cognitive impairment may lead to better prognostic prediction and yield novel treatment targets. The gut is implicated as a site of early pathology in PD. Early signs of PD pathology (alpha synuclein and Lewy body aggregates) are detected in the gastrointestinal tract years before motor symptoms manifest. Recent studies provide evidence that individuals with PD have an altered gut-bacterial composition (termed dysbiosis) relative to controls. To date, dysbiosis is linked to more severe motor symptoms and certain non-motor symptoms (constipation, REM behavioral sleep disorder) in PD, but the relationship between dysbiosis and cognitive impairment remains unknown. Animal studies support the hypothesis that microbiota composition play a direct role in cognitive impairment. Germ free (GF) mice demonstrate deficits in cognition. Specifically, findings suggest that a disrupted gut- microbial environment in conjunction with elevated stress hormones may create an imbalance of pro- inflammatory vs. anti-inflammatory cytokines that induces potentially reversible cognitive impairments. In human studies among individuals with PD, neuroinflammatory markers are associated with cognitive impairment. However, the relationship between dysbiosis, neural inflammation and cognitive functioning remains unknown. This model has incredible clinical implications, as microbiota dysbiosis may represent a reversible risk factor for cognitive impairment. The proposed study will examine the hypothesis that dysbiosis contributes to increased neuroinflammation and cognitive impairment. Microbiota composition/function, neuroinflammatory markers and cognitive functioning will be examined in 100 participants with PD. Analyses of microbiota composition/function will examine abundance of amplicon sequence variants (ASVs; 16s), bacterial species/strains (metagenomics), microbial genes, and functional pathways. We hypothesize that microbiota composition/function will be associated with inflammatory markers (e.g. interleukin-6, tumor necrosis factor-alpha, c-reactive protein) and cognitive impairment.

Condition or Disease Intervention/Treatment Phase

    Study Design

    Study Type:
    Observational
    Anticipated Enrollment :
    100 participants
    Observational Model:
    Case-Only
    Time Perspective:
    Cross-Sectional
    Official Title:
    Microbiome Composition and Function Contributes to Cognitive Impairment and Neuroinflammation in Parkinson's Disease
    Actual Study Start Date :
    Apr 30, 2021
    Anticipated Primary Completion Date :
    Apr 1, 2026
    Anticipated Study Completion Date :
    Apr 1, 2026

    Arms and Interventions

    Arm Intervention/Treatment
    Parkinson's

    Those with Parkinson's Disease

    Outcome Measures

    Primary Outcome Measures

    1. Cognitive Impairment [4 hours]

      Cognitive functioning as measured by a composite measure (average) of all neuropsychological tests

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    55 Years to 85 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Parkinson's Disease
    Exclusion Criteria:
    • Use of antibiotics or immunosuppressant medications within the last 3 months, history of psychiatric hospitalizations, stroke, epilepsy, head injury resulting in a loss of consciousness for more than 30 minutes, Alzheimer's disease or other significant brain injury or neurologic event, history of inflammatory gastrointestinal diseases such as Crohn's, Celiac's disease or irritable bowel syndrome

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 California State University San Bernardino San Bernardino California United States 92407

    Sponsors and Collaborators

    • California State University, San Bernardino
    • National Institutes of Health (NIH)
    • National Institute of Neurological Disorders and Stroke (NINDS)

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Jacob Jones, Clinical Psychologist, California State University, San Bernardino
    ClinicalTrials.gov Identifier:
    NCT05419453
    Other Study ID Numbers:
    • SC3NS124906
    First Posted:
    Jun 15, 2022
    Last Update Posted:
    Jun 15, 2022
    Last Verified:
    Jun 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Jacob Jones, Clinical Psychologist, California State University, San Bernardino
    Parkinson Disease
    Cognition
    Additional relevant MeSH terms:
    Parkinson Disease
    Cognitive Dysfunction

    Study Results

    No Results Posted as of Jun 15, 2022