Microbiota Mediated Flavonoid Metabolites for Cognitive Health
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age50+
SponsorUniversity of Ulster
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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).
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
Polyphenol Supplement
Dietary supplementJuice Plus Essentials, Berry Blend Capsules
Placebo Supplement
Dietary supplementMicronutrient matched placebo
Treatment groups
100 Participants
are divided into 2 treatment groupsGroup A: Polyphenol SupplementExperimental treatment 1 intervention
Group B: Placebo SupplementPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
Differences in Polyphenol-derived metabolite concentrations pre, mid, & post intervention - stool
Measurement of metabolomics via stool specimen.
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)2
Differences in Polyphenol-derived metabolite concentrations pre, mid, & post intervention - blood
Measurement of metabolomics via blood specimen.
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).3
Differences in microbiome levels pre, mid, & post intervention - Stool
16S RNA sequencing to measure microbiome levels via stool specimen.
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).4
Differences in microbiome levels pre & post intervention - Blood
16S RNA sequencing to measure microbiome levels via blood specimen.
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).Secondary outcomes
1
Differences in tryptophan-associated metabolite profiles pre, mid, and post intervention - Stool
Measurement of tryptophan-associate metabolite profiles via stool specimen.
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).2
Differences in Bile Acid's (BA's) pre, mid, & post intervention - Stool
Measurement of BA's via stool specimen.
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).3
Differences in Inflammatory markers pre, mid, & post intervention - Blood
Measurement of inflammatory markers via blood specimen.
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).4
Differences in Alzheimer's Disease (AD) markers pre, mid, & post intervention - Blood [Time
Measurement of AD markers via blood specimen.
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).Other outcomes
1
Differences in Multimodal Brain Signatures pre, mid, & post intervention
Neuroimaging of participants brain via magnetic resonance imaging (MRI) procedure.
Time frame
Measured thrice, once at baseline (week 0), mid-study (month 6), and final 12month appointment (month 12) visit.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
University of Ulster
Lead sponsor
University of Parma
Collaborator
University College Cork
Collaborator
National Institute on Aging (NIA)
Collaborator
University of California, Los Angeles
Collaborator
Source ClinicalTrials.gov