The Influence of the Microbiome on the Pharmacokinetics of Flavan-3-ols

NCT05113498 | Completed DMC

• 1 other identifier: BC-09585
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Cocoa beans are of major interest due to their various beneficial health effects, indicated to be caused by its cocoa flavan-3-ols. (-)-Epicatechin is the most abundant flavan-3-ol in these cocoa beans. Its metabolization in the colon results in bioactive valerolactone and valeric acid metabolites and derivatives after phase II metabolism. Interindividual differences in health effects following (-)-epicatechin consumption are observed, which are suggested to be caused by large interindividual differences in bioavailable metabolite concentrations. As the colonic microbiota is responsible for the metabolization of \~70% of total (-)-epicatechin intake, and \~42% of total (-)-epicatechin intake leads to valerolactone and valeric acid metabolites, it is hypothesized that the large interindividual variation in microbial gut composition is responsible for the heterogeneity in metabolite concentration and in its subsequent health effects. Furthermore, individuals can be stratified into two pharmacotypes, slow and fast microbial metabolizers, which can produce metabolites at different rates. The aim of this single-arm study is to investigate if the microbial composition in the gut determines the rate and extent of metabolization, following an acute consumption of about 160mg of pure (-)-epicatechin. The pharmacokinetics of the (-)-epicatechin metabolites will be followed in plasma over 48h with a focus on the first fifteen hours and potentially in urine over 24h. Valerolactone and valeric acid metabolite profiles in plasma and urine will be obtained by Q-TOF-LC-MS. The microbial fingerprint of each individual will be obtained via DNA extraction, flow cytometry and 16s rRNA sequencing of fecal samples.

Conditions

Diet Modification

Keywords

Valerolactones; (-)-Epicatechin; Microbiota; Pharmacokinetics; Interindividual differences; Q-TOF-LC-MS

Outcome Measures

Primary Outcomes (2)

• Assessing the formation of phase II valerolactone and valeric acid metabolites over time in blood.

  Assessing the concentration of colonic valerolactone and valeric acid metabolites over time in blood by Q-TOF-LC-MS, after the consumption of 160g pure (-)-epicatechin, to identify poor and extensive metabolizers.

  48 hours

• Identification of the bacteria on genus level in fecal samples of participants.

  All bacteria in the fecal samples of participants will be identified by 16S rRNA gene-based analysis on genus level.

  Baseline

Study Arms (1)

(-)-Epicatechin

EXPERIMENTAL

(-)-Epicatechin supplementation

Dietary Supplement: (-)-Epicatechin

Interventions

(-)-Epicatechin DIETARY_SUPPLEMENT

Administration of a capsule with 150 mg of pure (-)-epicatechin after 48h low-flavanol diet.

(-)-Epicatechin

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy
• Stable diet
• Stable exercise regimen

You may not qualify if:

• The use of antibiotics, pre- and probiotics in the last six months
• The use of chronic medication
• The use of any medication in the last 2 weeks
• Diarrhea in last 2 weeks
• Recent blood donations
• Vegan or vegetarian diets
• Smoking
• Chronic pathology or gastrointestinal disorders

Sponsors & Collaborators

• University Ghent: lead

Study Sites (1)

University Ghent

Ghent, East-Flanders, 9000, Belgium

Location

Related Publications (1)

• Mena P, Bresciani L, Brindani N, Ludwig IA, Pereira-Caro G, Angelino D, Llorach R, Calani L, Brighenti F, Clifford MN, Gill CIR, Crozier A, Curti C, Del Rio D. Phenyl-gamma-valerolactones and phenylvaleric acids, the main colonic metabolites of flavan-3-ols: synthesis, analysis, bioavailability, and bioactivity. Nat Prod Rep. 2019 May 22;36(5):714-752. doi: 10.1039/c8np00062j.

  PMID: 30468210 BACKGROUND

MeSH Terms

Interventions

Catechin

Intervention Hierarchy (Ancestors)

Chromans; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Flavonoids; Chromones; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Ernst Rietzschel, PhD

  University Hospital, Ghent

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single-dose study where all participants consume one epicatechin supplement.

Study Record Dates

• First Submitted: October 15, 2021
• First Posted: November 9, 2021
• Study Start: November 1, 2021
• Primary Completion: April 26, 2022
• Study Completion: April 26, 2022
• Last Updated: April 27, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)