Microbiota Mediated Flavonoid Metabolites for Cognitive Health

NCT ID: NCT07226674

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-11-10

Study Completion Date

2028-01-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Cognitive Decline Cognitive Dysfunction

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Polyphenols Mediterranean Diet Gut Microbiome Alzheimer Disease

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Interventional Model
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Polyphenol Supplement

Juice Plus Essentials, Berry Blend Capsules

Group Type EXPERIMENTAL

Polyphenol Supplement

Intervention Type DIETARY_SUPPLEMENT

Juice Plus Essentials, Berry Blend Capsules

Placebo Supplement

Group Type PLACEBO_COMPARATOR

Placebo Supplement

Intervention Type DIETARY_SUPPLEMENT

Micronutrient matched placebo

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Polyphenol Supplement

Juice Plus Essentials, Berry Blend Capsules

Intervention Type DIETARY_SUPPLEMENT

Placebo Supplement

Micronutrient matched placebo

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Minimum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

University of Parma

OTHER

Sponsor Role collaborator

University College Cork

OTHER

Sponsor Role collaborator

National Institute on Aging (NIA)

NIH

Sponsor Role collaborator

University of California, Los Angeles

OTHER

Sponsor Role collaborator

University of Ulster

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Chris Gill, PhD

Role: PRINCIPAL_INVESTIGATOR

Ulster University, Human Intervention Studies Unit, Coleraine, Co. Londonderry, BT52 1SA, United Kingdom.

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Ulster University, Human Intervention Studies Unit

Coleraine, , United Kingdom

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United Kingdom

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Chris Gill, PhD

Role: CONTACT

Phone: +44 28 7012 3181

Email: [email protected]

Aoife Caffrey, PhD

Role: CONTACT

Phone: +44 (0) 28 701 23401

Email: [email protected]

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Aoife Caffrey, PhD

Role: primary

Role: backup

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

1R01AG081768-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

5R01AG081768-02

Identifier Type: NIH

Identifier Source: secondary_id

View Link

REC/25/0046

Identifier Type: -

Identifier Source: org_study_id