Microbiota Mediated Flavonoid Metabolites for Cognitive Health (MAEVE)

November 21, 2025 updated by: University of Ulster

MAEVE: Microbiota Mediated Flavonoid Metabolites for Cognitive Health

Globally, populations are ageing increasing the prevalence of Alzheimer's disease (AD), due to lack of effective treatments. The traditional Mediterranean diet, rich in fibre and polyphenols (PPs) can help prevent or delay cognitive dysfunction and preserve healthy brain structure and function. Cognitive decline is inversely associated with higher PP intakes (>421mg/day) i.e., total flavonoids, flavan-3-ols and flavonoid oligomers. The positive brain effects of flavonoid intake are likely mediated in part by gut microbial PP metabolites, consistent with the emerging role of the brain-gut microbiome (BGM) system in neurodegeneration. Our preliminary data indicate that circulating phenyl-γ-valerolactones (PVL), neuroprotective compounds exclusively produced by gut microbiota from flavan-3-ol rich foods18 are associated with delaying cognitive dysfunction. Intake of PPs change gut microbial composition and function, altering the physiology of the host's secondary bile acid (BA) pool through modulation of bacterial 7α-dehydroxylation of de-conjugated primary BAs into secondary BAs. This is noteworthy as 7α-dehydroxylation of BAs does not happen in the brain and because gut microbial BA metabolites have regulatory and signalling functions in the brain. The ratio between certain primary and secondary BAs is also dysregulated in AD with significantly lower serum concentrations of cholic acid (a primary BA) and increased levels of deoxycholic acid (a bacterially produced secondary BA). The increased ratio of cholic acid to deoxycholic acid is correlated with cognitive decline. Increased levels of tyrosine, tryptophan, purine, and tocopherol have also been identified in postmortem AD brains. However, specific pathways and mechanisms underlying these associations are unclear. In this multi-PI application by leaders in the field of BGM interactions, we leverage the collectively (NIH, HSC, SFI) funded Tripartite US-Ireland R&D Partnership Program to determine the mechanisms involved in PP intake on maintaining healthier cognitive and brain function, as mediated by gut microbiota metabolites of PP and BAs in 50+ year old elderly with enhanced AD risk.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

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

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United Kingdom
      • Coleraine, United Kingdom, BT52 1SA
        • Recruiting
        • Ulster University, Human Intervention Studies Unit
        • Contact:
        • Contact:
        • Principal Investigator:
          • Chris Gill, PhD

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • 50+ years
  • BMI ≥ 25 kg/m2
  • Enhanced risk of AD - defined as family history of AD, 1st degree family member
  • Habitually consume suboptimal diets such as typical Western diet (i.e., high in animal products, refined carbohydrates and processed food).
  • Subjects capable of and willing to comply with the protocol and to give their written informed consent.

Exclusion Criteria:

  • Cognitive impairment at time of recruitment into the study, as measured by the Mini Mental Status Exam (MMSE, score 25-30), and Clinical Dementia Rating (CDR, score=0) or Everyday Cognition Scale-12 (ECog-12, score<1.36 included).
  • Pre-existing psychosis or psychiatric conditions.
  • Currently receiving treatment for dementia.
  • History of substance abuse or cerebrovascular events.
  • Heavy use of tobacco (>1/2 pack per day)
  • Any intolerance or allergy documented or suspected to one of the components of the study products.
  • Have taken probiotics or antibiotic therapy within the last 1 month
  • Change in medication use in the last 3 months.
  • Frailty, malnutrition, or food allergy/intolerance requiring special diets will also be excluded.
  • Following any specific diet (vegetarian, vegan, etc.)
  • Body weight at enrolment greater than 400lbs due to weight restrictions on the MRI table.
  • Pregnant, breastfeeding, postpartum for less than 6 months, or unwilling to practice birth control during participation in the study.
  • Unable to safely participate in the MRI (claustrophobia, presence of devices affected by MRI such as pacemakers, neurostimulators, or metallic foreign body, etc.)
  • Chronic pain.
  • Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
  • Having a psychological or linguistic inability to sign the informed consent;
  • Under legal protection (guardianship, wardship) or deprived from his rights following administrative or judicial decision;
  • Subject participating in another biomedical study or participation in another study within the 3 months before entry into this study.

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

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo Supplement
Dietary supplement: Placebo Supplement
Micronutrient matched placebo
Experimental: Polyphenol Supplement
Juice Plus Essentials, Berry Blend Capsules
Dietary supplement: Polyphenol Supplement
Juice Plus Essentials, Berry Blend Capsules

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Differences in Polyphenol-derived metabolite concentrations pre, mid, & post intervention - blood
Time Frame: Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
Measurement of metabolomics via blood specimen.
Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
Differences in microbiome levels pre & post intervention - Blood
Time Frame: Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
16S RNA sequencing to measure microbiome levels via blood specimen.
Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
Differences in Cognitive Measures pre, mid, & post intervention - Executive Function
Time Frame: Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
Administration of a standardized Trails A & B; participants ability to connect dots, in order, as quickly as possible.
Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
Differences in Cognitive Measures pre, mid, & post intervention
Time Frame: Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
Differences in Polyphenol-derived metabolite concentrations pre, mid, & post intervention - stool
Time Frame: Collected three times by the participant at home, once at baseline (week 0), once at mid-study (month 6), and once at the final 12month appointment (month 12)
Measurement of metabolomics via stool specimen.
Collected three times by the participant at home, once at baseline (week 0), once at mid-study (month 6), and once at the final 12month appointment (month 12)
Differences in microbiome levels pre, mid, & post intervention - Stool
Time Frame: Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
16S RNA sequencing to measure microbiome levels via stool specimen.
Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
Differences in microbiome levels pre, mid, & post intervention - Stool
Time Frame: Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
Shotgun metagenomics, sequencing to measure microbiome levels via stool specimen.
Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
Differences in microbiome levels pre, mid, & post intervention - Blood
Time Frame: Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
Shotgun metagenomics, sequencing to measure microbiome levels via stool specimen.
Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
Differences in Cognitive Measures pre, mid, & post intervention - Executive Function
Time Frame: Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
Administration of a standardized Stroop Neuro-psychological test; participants ability to correctly identify colours when words are printed in conflicting ink colours.
Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
Differences in Cognitive Measures pre, mid, & post intervention
Time Frame: Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
Administration of a standardized arithmetic task; participants ability to complete quick mental math.
Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Differences in tryptophan-associated metabolite profiles pre, mid, and post intervention - Stool
Time Frame: Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
Measurement of tryptophan-associate metabolite profiles via stool specimen.
Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
Differences in Bile Acid's (BA's) pre, mid, & post intervention - Stool
Time Frame: Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
Measurement of BA's via stool specimen.
Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
Differences in Inflammatory markers pre, mid, & post intervention - Blood
Time Frame: Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
Measurement of inflammatory markers via blood specimen.
Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
Anthropometrics - BMI
Time Frame: Measured three times, once at each in-clinic appointment (week 0, month 6, month 12)
Measurement of height(in) and weight(lbs), used to calculate body mass index (BMI)
Measured three times, once at each in-clinic appointment (week 0, month 6, month 12)
Anthropometrics - waist and hip circumference
Time Frame: Measured three times, once at each in-clinic appointment (week 0, month 6, & month 12)
Measurement of waist and hip circumference (cm)
Measured three times, once at each in-clinic appointment (week 0, month 6, & month 12)
Systolic and Diastolic Blood Pressure
Time Frame: Measured three times, once at each in-clinic appointment (week 0, month 6, month 12).
Measurement of the pressure of circulating blood at rest
Measured three times, once at each in-clinic appointment (week 0, month 6, month 12).
Differences in Alzheimer's Disease (AD) markers pre, mid, & post intervention - Blood [Time
Time Frame: Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
Measurement of AD markers via blood specimen.
Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
Questionnaire Data
Time Frame: Collected 3 times (1) before beginning the dietary supplement, (2) mid-study month 6, (3) end of study month 12.
Use of validated surveys to assess ingestive behaviours, social isolation, stress, health, physical activity, etc., self-reported by the participant at home.
Collected 3 times (1) before beginning the dietary supplement, (2) mid-study month 6, (3) end of study month 12.
Monthly Questionnaire Data
Time Frame: Collected 3 times (1) before beginning the dietary supplement, (2) mid-study month 6, (3) end of study month 12.
Collected once a month for the duration of the study (12months).
Collected 3 times (1) before beginning the dietary supplement, (2) mid-study month 6, (3) end of study month 12.

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Differences in Multimodal Brain Signatures pre, mid, & post intervention
Time Frame: Measured thrice, once at baseline (week 0), mid-study (month 6), and final 12month appointment (month 12) visit.
Neuroimaging of participants brain via magnetic resonance imaging (MRI) procedure.
Measured thrice, once at baseline (week 0), mid-study (month 6), and final 12month appointment (month 12) visit.

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Ulster

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of California, Los Angeles
National Institute on Aging (NIA)
University College Cork
University of Parma

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Chris Gill, PhD, Ulster University, Human Intervention Studies Unit, Coleraine, Co. Londonderry, BT52 1SA, United Kingdom.

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 (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 25, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 7, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 7, 2025

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 10, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 24, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 21, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • REC/25/0046
  • 1R01AG081768-01 (U.S. NIH Grant/Contract)
  • 5R01AG081768-02 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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